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Biomedical subjects

C Letoublon

Publications and source records attributed to C Letoublon.

At least 19 recordsLinked to original sources
PubMed2006

EGFR in colorectal cancer: more than a simple receptor.

BACKGROUND: Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR). METHOD: The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon-colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis). FINDINGS: A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue. INTERPRETATION: These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.

Aged↗
PubMed2005

[Laparostomy with vacuum pack technique].

The technique of abdominal wall closure by vacuum pack is described. Indications are essentially the abbreviated laparotomy or damage control (especially with abdominal packing), and the post traumatic abdominal compartment syndrome (in the treatment and prevention).

Abdominal Injuries↗
PubMed2001

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↗
PubMed2001

A new ileal pouch salvage technique.

Restorative proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the surgical treatment of ulcerative colitis. Fistulas originating from the ileal pouch are uncommon but serious complications, sometimes leading to failure of the operation. We describe a technique to treat and salvage a pouch involved in a chronic fistulating ileal J-pouch-anal anastomosis by disconnecting the pouch, turning it inside out after repair, and reanastomosing it to the dentate line.

Adult↗
PubMed2000

Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: A multicenter phase III trial.

OBJECTIVE: To evaluate the results of a prospective multicenter randomized study of adjuvant intraperitoneal 5-fluorouracil (5-FU) administered during 6 days shortly after resection of stages II and III colon cancers. SUMMARY BACKGROUND DATA: Systemic adjuvant chemotherapy improves the survival of patients with stage III colon cancer receiving treatment for 6 months. Intraperitoneal chemotherapy theoretically combines peritoneal and hepatic effects. METHODS: After resection, 267 patients were randomized into two groups. Patients in group 1 (n = 133) underwent resection followed by intraperitoneal administration of 5-FU (0.6 g/m2/day) for 6 days (day 4 to day 10). These patients also received intravenous 5-FU (1 g) during surgery. Patients in group 2 underwent resection alone (n = 134). RESULTS: In group 1, 103 patients received the total dose, 18 received a partial dose as a result of technical or tolerance problems, and 12 did not receive the chemotherapy. Rates of surgical death and complications were similar in both groups. Tolerance to treatment was excellent or fair in 97% of the patients and poor in 3%. After a median follow-up of 58 months, 5-year overall survival rates were 74% in group 1 and 69% in group 2; disease-free survival rates were 68% and 62%, respectively. Survival curves were superimposed until 3 years after treatment and began diverging thereafter. Among patients receiving the full treatment, the 5-year disease-free survival rate was improved in the treatment group in patients with stage II cancers but was unchanged in patients with stage III cancers. CONCLUSIONS: Chemotherapy with intraperitoneal 5-FU administered during a short period after surgery was well tolerated but was not sufficient to reduce the risk of death significantly. However, it reduced the risk of recurrence in stage II cancers. These results suggest that it should be associated with systemic chemotherapy to reduce both local and distant recurrences.

Adenocarcinoma↗
PubMed1999

Specific vascular complications of orthotopic liver transplantation with preservation of the retrohepatic vena cava: review of 1361 cases.

OBJECTIVE: The objective of this study was to describe the complications specifically related to orthotopic liver transplantation (OLT) with preservation of the inferior vena cava and to their therapeutic management. This preservation technique has considerably influenced the surgical phases of liver transplantation, increasing hepatectomy time and modifying the number of vascular anastomoses. METHODS: Our retrospective multicentric study, based on data from 1361 adult patients that had undergone orthotopic liver transplantation with preservation of the inferior vena cava in France between 1991 and 1997, analyzed the concomitant surgical complications. Type of cavo-caval anastomosis performed (piggyback, end-to-side, or side-to-side), use of a temporary portacaval anastomosis, technique-related complications, and mortality, were investigated. RESULTS: Cavo-caval anastomosis was side-to-side in 50.6% of cases (n=689), piggyback in 42.7% (n=582), and end-to-side in 6.6% (n=90). In total, 882 temporary portacaval anastomosis were carried out. Fifty-five patients presented with one or more complications related to the preservation of the inferior vena cava technique; i.e., overall morbidity was 4.1% (55/1361). Overall mortality was 0.7% (10/1361). Mortality rate for patients who presented with surgical complication was 18%. A total of 64 complications were recorded: 57 (89%) were in the perioperative or immediate postoperative period and 7 (11%) were postoperative. CONCLUSIONS: These retrospective, descriptive results show significant advantages in favor of side-to-side anastomosis in terms of vascular complications. Certain factors should be evaluated specifically at pretransplant assessment to prevent certain serious complications; principally, these are anatomic factors of the recipient (inferior vena cava included in segment I, anatomic abnormalities of the inferior vena cava) and graft size. Depending on these factors, surgeons must be able to adapt the orthotopic liver transplantation, either before or during orthotopic liver transplantation, preferring the standard technique.

Anastomosis, Surgical↗
PubMed1999

Use of grafts procured from organ transplant recipients.

BACKGROUND: Massive intracerebral bleeding may cause brain stem death in transplant (Tx) recipients early or late postTx. We addressed the question as to whether Tx recipients may safely be used as organ donors. In particular, it is feared that exposure to immunosuppressive drugs may render those organs unsuitable for Tx. METHODS: We reviewed two case reports of liver grafts procured from Tx patients. In addition, we conducted a survey within United Kingdom Transplant Support Service Authority (UKTSSA) to delineate the UK experience in that area. RESULTS: Donor 1 was an 50-year-old heart Tx recipient who became brain stem dead due to cerebral bleeding 8 months postTx. His liver was used in an 55-year-old patient with PBC who is alive and well more than 22 months postTx. Donor 2 was a 22-year-old kidney Tx patient who developed cerebral bleeding 4 years postTx. His liver was used in a 65-year-old patient with PBC who is doing well more than 27 months postTx. During the study period of 1989-1995, 13 organs (9 kidneys, 3 hearts, 1 liver) were procured from 6 brain stem dead Tx patients (3 long, 2 heart, and 1 kidney Tx patients). Seven recipients are enjoying satisfactory graft function 1 to 7 years postTx; one kidney Tx recipient was relisted 4 years postTx due to chronic rejection; five functionning grafts were lost to patient death; primary nonfunction was seen in one heart Tx recipient. CONCLUSIONS: Tx patients can be successfully used as organ donors. In particular, chronic exposure to immunosuppression is not per se a contraindication to donation. Tx physicians confronted with the rare and tragic event of brain stem death in a Tx patient should not a priori exclude these patients from donation.

Adult↗
PubMed1999

[Current treatment of closed injuries of the liver: benefits and pitfalls].

STUDY AIM: The management of blunt hepatic trauma has been modified by the development of conservative methods. Risks and pitfalls of this new approach must be determined. PATIENTS AND METHODS: From January 1985 to September, 1998, 130 patients with blunt hepatic trauma were treated by the same team. Among them, 38 patients were referred from another centre (21 already having undergone operations). Eighty patients (61%) had an initial non operative management and 50 patients (39%) underwent emergency laparotomy. Perihepatic packing was performed in 24 patients, hepatic sutures in 22, limited hepatic resection in six, and major hepatectomy in two patients only. RESULTS: There were three deaths in the non operative management group (mortality rate: 3.5%) and 11 patients required a secondary laparotomy: four for haemorrhage, one for enteric injury, two for acute pancreatitis, one for bile leakage, one for subphrenic abscess, one for acute cholecystitis. There were 14 deaths in the emergency laparotomy group (mortality rate: 28%), including four intraoperative deaths due to haemorrhage and two due to abdominal compartment syndrome. CONCLUSIONS: In the nonoperative management group a close clinical survey of the patient is necessary and a secondary laparotomy often indicated. In the operative management group, early packing requires reintervention if the patient is unstable. Alternative means of temporary closure may allow coverage without tension in order to avoid the abdominal compartment syndrome.

Adolescent↗
PubMed1998

EBV-B cells as antigen presenting cells in characterization of the self/donor context of allorecognition by T lymphocytes.

Alloreactivity is caused by T cell recognition of foreign histocompatibility antigens according to two models: (i) indirect recognition, in which processed allogeneic antigens are presented by self-major histocompatibility complexes like any other foreign antigen, and (ii) direct recognition, where the foreign MHC itself is recognized breaking the T cell recognition rule of self-restriction. This paper uses these two cases of alloantigen presentation as illustrative examples to investigate (i) the capacity of Epstein-Barr virus-transformed B cells (EBV-B cells) to process alloantigens, and (ii) in vitro assays with EBV-B cell lysate as a source of alloantigen, in order to characterize alloreactive T cell populations. A microculture system was established using donor EBV-B cell lysate as a source of the allogeneic antigen and donor or recipient EBV-B cells as antigen presenting cells to investigate whether alloantigen is recognized by effector T cells from the recipient. T lymphocytes produced after expansion in the presence of interleukin-2 from four samples of liver biopsies (three patients) and four samples of bronchoalveolar lavages (four patients) were used as effector cells. Upon human leucocyte antigen class II typing, these expressed the patient phenotype. When the T lymphocytes were from liver grafts, the recognition involved donor antigens presented by donor EBV-B cells (direct recognition). On the other hand, when the T lymphocytes were cultured from lung grafts, they mainly recognized antigens of donor EBV-B cell lysates in a self-restricted context (indirect recognition). These data suggest that EBV-B cells can provide allogeneic determinants recognized by T cells in donor or self-contexts, i.e. through either direct or indirect recognition.

Adult↗
PubMed1997

Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data.

Thymidylate synthase (TS) is the main target for fluorouracil (FU). Optimal cellular concentrations of reduced folates in polyglutamated forms [via folylpolyglutamate synthetase (FPGS)] are necessary for achieving maximal TS inhibition. The aim of this multicentric prospective study was to analyze the link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities. Forty-four advanced colorectal cancer patients (15 women and 29 men; median age 63, range, 27-78 years) receiving a standard FU-folinic acid protocol were included. A single hepatic tumoral biopsy was obtained systematically at the time of diagnosis. For 24 patients, a biopsy in the primary colon tumor was available. TS and FPGS activities were measured by radioenzymatic assays. Clinical response on hepatic metastases was 1 complete response, 12 partial responses, 14 stabilizations, and 17 progressions. In hepatic biopsies, TS activity (median, 185; range, <10-3111 fmol/min/mg protein) and FPGS activity (median, 1270; range, <400-3730 fmol/min/mg protein) exhibited a wide variability. TS activity in primary tumors (median, 461; range, 35-2565 fmol/min/mg protein) was significantly higher than in hepatic metastases. No difference was observed between primaries and metastases for FPGS. FPGS activity expressed in liver metastases was significantly correlated to that expressed in primaries. The distribution of TS activity in liver metastases was not significantly different between responsive and nonresponsive patients. However, FPGS activity measured in liver metastases was significantly higher in responsive patients (median, 1550 fmol/min/mg protein) than in nonresponsive patients (median, 1100 fmol/min/mg protein). A discriminant analysis revealed that 24 of the 25 patients exhibiting a liver FPGS activity </=1100 fmol/min/mg protein and/or a liver TS >320 fmol/min/mg protein were nonresponding patients. These data establish for the first time the potential importance of tumoral FPGS activity for assessing FU-folinic acid responsiveness in the clinical setting.

Adult↗
PubMed1996

[Vascular surgery and organ transplantation].

Among the recent advances in organ transplantation, the introduction of cryropreservation fluids in 1989 has allowed routine protection against ischemia over prolonged periods. There remain however several obstacles which can compromise graft survival and consequently lead to second transplantations and increased organ demand. Vascular complications are one of these complications. In many cases, close collaboration between transplantation surgery and the vascular surgery teams could reduce the number of problems. The aim of this work was to study situations in which collaboration could be useful. There are three areas of particular interest: kidney transplantations, liver transplantations and obviously, multiple organ transplantations.

Humans↗
PubMed1994

Serum levels of pancreatitis-associated protein as indicators of the course of acute pancreatitis. Multicentric Study Group on Acute Pancreatitis.

BACKGROUND/AIMS: The pancreatitis-associated protein (PAP) is undetectable in normal pancreatic secretion and overexpressed in the acute phase of pancreatitis. We investigated whether serum PAP could be an indicator of the course of acute pancreatitis. METHODS: Serum PAP was retrospectively monitored in 98 patients with acute pancreatitis during their stay in the hospital. Patients were classified according to the severity of their disease as group I (< or = 1 complication), group II (> or = 2 complications), or group III (lethal pancreatitis). RESULTS: At admission, 34% of patients, all from group I, had normal PAP values (< 10 micrograms/L). None of them developed complications. They had a significantly shorter stay in the hospital than patients with elevated PAP (6.2 days vs. 14.9 days). In all patients, serum PAP increased after admission to a maximum, which correlated significantly to the severity of the disease. Average peak values were 22.2 micrograms/L and 240.0 micrograms/L in group I patients with normal or high PAP at admission, 963.0 micrograms/L and 1436.0 micrograms/L in groups II and III. Serum PAP decreased steadily during recovery. CONCLUSIONS: Monitoring serum PAP in patients with acute pancreatitis would provide (1) at admission, selection of most patients who will not develop complications; (2) a dynamic assessment of severity; and (3) anticipation of the patient's recovery.

Acute Disease↗