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Marc Pocard

Publications and source records attributed to Marc Pocard.

At least 19 recordsLinked to original sources
PubMed2007

Establishment of human colon cancer cell lines from fresh tumors versus xenografts: comparison of success rate and cell line features.

Obtaining representative human colon cancer cell lines from fresh tumors is technically difficult. Using 32 tumor fragments from patients with colon cancer, the present study shows that prior xenograft leads to more efficient cell line establishment compared with direct establishment from fresh tumors (P < 0.05). From 26 tumor specimens, we successfully established 20 tumor xenografts in nude mice (77%); among 19 of these xenografts, 9 (47%) led to cell lines, including four from liver metastases. Only 3 of 31 tumor specimens (9.7%) grew immediately in vitro, and all were derived from primary tumors. To compare major phenotypic and genotypic characteristics of human colon cancer cell lines derived from the same tumor fragment using two protocols, the two pairs of cell lines obtained from 2 of 32 tumor fragments were extensively studied. They displayed similar morphology and were able to form compact spheroids. Chemosensitivity to 5-fluorouracil, CPT11, and L-OHP differed between cell lines obtained from patient tumors and those derived from xenografts. Matched cell lines shared a common core of karyotype alterations and distinctive additional chromosomal aberrations. Expression levels of genes selected for their role in oncogenesis evaluated by real-time quantitative PCR were found to be statistically correlated whatever the in vitro culture model used. In conclusion, xenotransplantation in mice of tumor fragments before establishment of cell lines enables generation of more novel human cancer cell lines for investigation of colon cancer cell biology, opening up the opportunity of reproducing the diversity of this disease.

Animals↗
PubMed2006

Peritoneal carcinomatosis of colorectal origin.

PURPOSE: Complete resection of macroscopic colorectal peritoneal carcinomatosis (PC), followed by intraoperative intraperitoneal chemohyperthermia (IPCH) to treat residual microscopic disease achieves cure in some patients. We report long-term results concerning survival of a phase II study using oxaliplatin (LOHP). PATIENTS AND METHODS: From June 1998 to December 2003, thirty patients with macroscopic colorectal PC underwent complete resection of PC followed by IPCH with LOHP performed in an open abdominal cavity. The dose of LOHP was 460 mg/m2 in 2 L/m2 of iso-osmotic 5% dextrose, over 30 min at an intraperitoneally homogenous temperature of 43 degrees C and at a flow rate of 2 L/min in the continuous closed circuit. During the hour preceding IPCH, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously. All patients received neoadjuvant and adjuvant systemic chemotherapy. RESULTS: Mean peritoneal tumor extension (Sugarbaker's Score) was 14.3 +/- 3.8, median operative duration, 450 min, and median blood loss, 940 mL. Eleven (37%) patients had associated extra-peritoneal lesions which were resected during the same procedure. There were no postoperative deaths and grade 2-3 morbidity (requiring specific treatment) was 40%. Median follow-up was 55 months (range: 31-84). Twenty-two patients (73%) relapsed after a median interval of 14 months, but 7 of them (32%) were amenable to curative repeat surgery. At 3 and 5 years, overall survival rates (95% confidence interval) were 53% (9-72), and 48.5% (31-66) respectively. At 3 and 5 years, disease-free survival rates were 41.5% (27-59), and 34% (19-52) respectively. Median survival was 60.1 months. CONCLUSION: When feasible, this treatment modality yields a 5-year survival rate of 48.5%, with median survival attaining 60.1 months.

Adult↗
PubMed2005

Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect.

BACKGROUND: The presence of extrahepatic disease (EHD) is considered a contraindication to hepatectomy in patients with colorectal liver metastases. After resection, the prognosis is based more on the total number of resected metastases (located inside and outside the liver) than on the site of these metastases (only inside the liver or not). METHODS: A total of 308 patients with colorectal cancer underwent hepatectomy, and 84 (27%) also underwent resection of miscellaneous EHD. The study was a prospective data registration and retrospective analysis. When considering the total number of resected metastases, each liver metastasis and each EHD location was counted as one lesion. Univariate and multivariate analyses were performed. RESULTS: The median follow-up was 99 months. The overall 5-year survival rate was 32%. In the multivariate analysis, the total number of metastases (inside or outside the liver) had a greater prognostic value than the criterion "presence or absence of EHD." Considering the total number of resected metastases (whatever their site), 5-year survival rates were 38% (SD: 4%) in the group with one to three metastases, 29% (SD: 5%) in patients with four to six metastases, and 18% (SD: 5%) in patients with more than six metastases (P = .002). A very simple prognostic score based on sex and the total number of metastases is proposed. CONCLUSIONS: EHD, when resectable, is no longer a contraindication to hepatectomy. More importantly, the total number of the metastases, whatever their location, has a stronger prognostic effect than the site of these metastases.

Adolescent↗
PubMed2005

ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer.

PURPOSE: The aim of our study was to assess whether the polymorphism of the nucleotide excision repair enzyme, excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), had an effect on the tumor response in patients treated with standard chemotherapy regimens for a metastatic colorectal cancer. We have studied the synonymous polymorphism that causes a single nucleotide change C to T at codon 118 converting a codon of common usage (AAC) to a less used codon (AAT), both coding asparagine. This change results in a decreased ERCC1 gene expression, which impairs repair activity. EXPERIMENTAL DESIGN: Ninety-one patients with a median age of 55.1 years treated for a metastatic colorectal cancer were included in our retrospective study. The ERCC1 polymorphism was analyzed in the normal tissue of all patients. RESULTS: Twenty (22%) were homozygous for AAC codon (C/C genotype), 30 were (33%) homozygous for AAT codon (T/T genotype), and 41 (45%) were heterozygous (C/T genotype). The objective response rate to oxaliplatin in combination with 5-fluorouracil (5-FU) was significantly higher in the T/T genotype group compared with the C/T and the C/C genotype groups (61.9%, 42.3%, and 21.4%, respectively; P = 0.018). By contrast, no significant difference was observed when patients were treated with either 5-FU alone (45%, 29.2%, and 33.3%, respectively; P = 0.407) or in combination with irinotecan (46.1%, 25.0%, and 27.3%, respectively; P = 0.305). CONCLUSIONS: Our observations allowed us to define the first useful predictive criterion for oxaliplatin/5-FU response in patients with metastatic colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Inguinal canal as an anatomic sanctuary site of relapse in peritoneal carcinomatosis previously treated with intraperitoneal chemotherapy.

Early postoperative intraperitoneal chemotherapy (EPIC) and intraoperative peritoneal hypertermic chemotherapy (IPHC) are used in addition with cytoreductive surgery to treat with curative intent peritoneal carcinomatosis arising from colorectal adenocarcinomas. Three patients with such a disease were treated with perioperative intraperitoneal chemotherapy in addition to cytoreductive surgery and presented isolated local recurrence located in the inguinal canal (round ligament in two and spermatic cord in one). All these patients were treated by local surgical excision. No patient showed evidence of intra-abdominal recurrence at the last follow-up, but one developed pulmonary metastasis. When communicating with the peritoneal cavity, the inguinal canal may act as a sanctuary site for peritoneal carcinomatosis, since it is not totally soaked by the intraperitoneal chemotherapy solution. A local recurrence is thus possible. New clinical presentations such as this one have first to be described in order to improve patient follow-up.

Adenocarcinoma, Mucinous↗
PubMed2005

Impact of the extent and duration of cytoreductive surgery on postoperative hematological toxicity after intraperitoneal chemohyperthermia for peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis (PC) is a major disease, currently treated using complete cytoreductive surgery and intraperitoneal chemohyperthermia (IPCH). Morbidity is a significant limitation of this procedure, usually related to the extent of surgery, and hematological toxicity, which is considered as dependent upon the chemotherapy dosage alone. The aim of our study was to investigate whether surgery alone had an impact on the hematological toxicity associated with the standardized drug protocol that we routinely prescribed. METHODS: Data were prospectively recorded from 83 consecutive patients who underwent complete cytoreductive surgery followed by IPCH with intraperitoneal oxaliplatin (360 mg/m(2)) and irinotecan (360 mg/m(2)), in 2 L/m(2) of dextrose over 30 min at 42-45 degrees C, using the Coliseum technique. Sixty minutes prior to IPCH, patients also received an intravenous perfusion of leucovorin (20 mg/m(2)) and 5-fluorouravyl (400 mg/m(2)). The doses and volume of IPCH were determined on the basis of the body surface area, so that all patients received the same concentration of drugs. Severe aplasia were defined as a leucocyte count of <500/ml, platelets <50,000/ml, and reticulocytes <6.5 g Hb/L. RESULTS: Postoperatively, severe aplasia was seen in 40 of the 83 patients (48%). There was no difference in the characteristics of patients with and without aplasia, other than the extent of surgery. The incidence of severe aplasia was only related to the duration of surgery (537 min in the aplastic group versus 444 min in the non aplastic group) (P = 0.002), and to the extent of the peritoneal disease (peritoneal index of 19.5 in the aplastic group, vs. 15.3 in the nonaplastic group) (P = 0.02). CONCLUSION: We report for the first time that the duration of surgery may increase the incidence of hematological toxicity following intraperitoneal chemotherapy. We also hypothesized that intra- and postoperative transient biochemical disorders, such as hypoalbuminemia, hemodilution, liver, and renal insufficiency and stress can be involved in this process. These hypotheses may allow improved postoperative care.

Adult↗
PubMed2005

Hepatectomy plus intraoperative radiofrequency ablation and chemotherapy to treat technically unresectable multiple colorectal liver metastases.

BACKGROUND: Results and indications of intra-operative radiofrequency (RF) ablation of liver metastases (LM) are not well defined in the literature. AIM: To appreciate the survival rate of patients with strictly unresectable LM (defined on technical but not oncological criteria) when undergoing liver resection plus RF, along with optimal systemic chemotherapy. PATIENTS AND METHODS: Sixty three patients with technically unresectable LM (either >5, or bilateral with no sparing of at least one sector of the liver, or with tumor proximity to central major vascular structures) were treated. Extrahepatic metastases were also resected in 27% of patients. All patients received perioperative chemotherapy. The median follow-up was 27.6 months (range: 15-74). RESULTS: There was no postoperative mortality and the morbidity rate was 27%. The 2-year overall survival rate of the 63 patients was 67% with a median survival of 36 months. The local recurrence rates were similar for the three types of local treatments: 7.1% for the 154 RF ablations, 7.2% for the 55 wedge resections, and 9% for the 44 segmental anatomic resections (P = 0.216). Hepatic recurrences occurred in 71% of patients. CONCLUSION: The combination of anatomic segmental and wedge resections, RF ablation, and optimal chemotherapy in patients with technically unresectable LM results in a median survival of 36 months.

Adult↗
PubMed2005

Ex vivo sentinel lymph node study for rectal adenocarcinoma: preliminary study.

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7-38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0-3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.

Adenocarcinoma↗
PubMed2005

Quality of life of patients operated on for low rectal cancer: impact of the type of surgery and patients' characteristics.

PURPOSE: This study was designed to compare the impact of a permanent colostomy and sociodemographic characteristics on the quality of life of patients operated on for low rectal cancer. METHODS: A cross-sectional study was performed by use of the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires. Patients came to the hospital to fill out the self-administered questionnaire or were sent the questionnaire by mail, followed by a live or telephone interview. All patients had undergone one of four operations: low anterior resection with colorectal or coloanal anastomosis (non-stoma group), or abdominoperineal resection with pseudocontinent perineal colostomy (nonstoma group) or left lower quadrant colostomy (stoma group). RESULTS: A total of 132 patients were included for analysis and there were no missing data. For the majority of quality of life scores (26/29), there was no significant difference between stoma and nonstoma patients. However, stoma patients complained of diminished body image (P = 0.0022), and this was especially true for married (P = 0.0073) and less educated (P = 0.0014) patients at subgroup analysis. Stoma patients experienced greater financial worries (P = 0.0029), whereas nonstoma patients had greater gastrointestinal concerns (P = 0.0098). CONCLUSIONS: Although most quality of life scores between stoma and nonstoma patients were similar, significant differences regarding body image, finance, and gastrointestinal symptoms, especially for married and less educated patients, were noticed. These factors should be taken into account, along with oncologic criteria, to better tailor treatments to patients.

Adult↗
PubMed2005

Preoperative criteria of incomplete resectability of peritoneal carcinomatosis from non-appendiceal colorectal carcinoma.

OBJECTIVE: To analyse the causes of non resectability of peritoneal carcinomatosis (PC) of non-appendiceal colorectal carcinomas, discovered only at the time of the laparotomy. SUMMARY BACKGROUND DATA: The combination of a maximal cytoreductive surgery (resecting tumor deposits > 1 mm in diameter) with intraperitoneal chemohyperthermia results in cure a significant number of patients. Complete resection of the PC is the determining factor of this time-consuming and resource-consuming therapy. Unfortunately, it has not been possible, so far, to safely predict complete resectability before carrying out the laparotomy. METHODS: All patients with colorectal PC who had undergone a laparotomy in order to receive this new treatment, but who finally presented a non completely resectable PC were included in our study. Their preoperative parameters were retrospectively studied and compared to matched number of patients who had successfully undergone this treatment. RESULTS: 29 patients had incomplete resection PC at laparotomy. They were compared with 29 matched patients who underwent a complete resection of the PC. The factors predicting non resectability were, in decreasing order of frequency: presence or persistence of an ascitis just before the laparotomy (P = 0.0008), progression of the PC while on neo-adjuvant chemotherapy (P = 0.01), abnormal CT- imaging (P = 0.03), and sub-occlusive syndrome (P = 0.05). These parameters were partially inter-related. CONCLUSION: The persistence of ascitis and any progression of the disease while on chemotherapy are important predictive factors of incomplete resectability of non-appendiceal colorectal PC.

Carcinoma↗
PubMed2005

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal colorectal carcinomatosis: a newly validated standard whose contribution remains to be assessed].

Peritoneal carcinomatosis represent an advanced form of colorectal cancer but different of others metastatic pathways. However carcinomatosis was associated with stage M in the TNM classification, because of a very poor prognosis, actually resulting despite new chemotherapeutic agents of a single year of survival. In an estimated 30% of patients, no other tumour location can be found. Usually complete tumour resection can not be perform, resulting in the best time with a R1 procedure associated with microscopic residual disease. This is to eradicate microscopic residual disease that hyperthermic intraperitoneal chemotherapy (HIPEC) was proposed. First results of single unit published reported survival after 5 years and that the most important prognosis factor of survival was complete resection of the carcinomatosis (R1 resection). A phase III study publish in 2003 in the Journal of Surgical Oncology by the Zoetmulder's team confirm the phase II results and offer for the first time a factual impact with a level II of demonstration. Between 1998 and 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) or aggressive cytoreduction (incomplete for some patients) with HIPEC (mitomycin C during 90 minutes) followed by the same systemic chemotherapy regime. In the HIPEC arms, mortality was at 8 % and the median hospital admission was near one month. After a median follow-up period of 21 months, the median survival was 12 months in the standard therapy arm and 22 months in the HIPEC arm (p = 0.032). These results confirm prior reported non randomised study reporting median survival of 12 to 40 months. We had recently published the results of a phase II study including only patient with a R1 resection associated with HIPEC with oxaliplatin. This study had include 24 patients with an overall survival of 65% at 3 years. These survival result was the most prolonged never reported in the treatment of peritoneal colorectal carcinomatosis. HIPEC can be considered as a new standard even the exact place in clinical practice had to be more define because of alls recent progress are publish giving an important number of publications during the 2003-2004 years, some of them coming from French groups.

Carcinoma↗
PubMed2004

Local recurrences after intraoperative radiofrequency ablation of liver metastases: a comparative study with anatomic and wedge resections.

BACKGROUND: The indications and results of intraoperative radiofrequency ablation (RFA) of liver metastases (LMs) are not well defined in the literature and have never been compared with those of hepatectomy. The aim of the study was to appreciate the local recurrence rate of RFA in comparison with anatomic and wedge resection. METHODS: Eighty-eight patients with technically unresectable LMs were treated with curative intent. The LMs were treated by anatomic resection (40 patients, 213 LMs) when large, by wedge resection (64 patients, 99 LMs) when peripheral and small, and by RFA (88 patients, 227 LMs) when central and small. The median follow-up was 27.6 months (range, 15-74 months), and a total of 539 LMs were treated (median of 5 per patient). RESULTS: The local recurrence rates were 5.7% for the 227 RFAs, 7.1% for the 99 wedge resections, and 12.5% for the 40 anatomic resections (P =.216). Local recurrence rates after RFA were correlated with LMs larger than 30 mm (P <.001) and with LMs in direct contact with large vessels (P <.001). CONCLUSIONS: RFA is as efficient and safe as wedge or anatomic resections in terms of local control.

Adult↗
PubMed2004

Intraductal cooling of the main bile ducts during radiofrequency ablation prevents biliary stenosis.

BACKGROUND: Small-sized tumors sited closer than 15 mm to the central bile ducts cannot be destroyed by radiofrequency (RF) because the resulting heating causes destruction and stenosis of the bile ducts. STUDY DESIGN: Thirteen patients underwent intraoperative RF to treat tumors closer than 6 mm to a central bile duct. Stenosis prevention was achieved by cooling the main bile duct(s) (right, left, or both) with a 4 degrees C saline solution quickly infused by a catheter introduced inside the bile duct through a choledochotomy. Median followup after cooling was 19.7 months (range 6 to 42 months). RESULTS: There was no mortality and no RF-related morbidity. Twelve patients (92.3%) did not present any biliary stenosis. In one patient (7.7%) biliary stenosis was detected 6 months after RF. The patient was cirrhotic but did not require any treatment. One of the 13 patients had a local recurrence. CONCLUSIONS: The intraoperative cooling of central bile ducts prevents biliary stenosis efficiently when using RF to destroy tumors closer than 5 mm to the bile duct. This new technique decreases the contraindications for the use of RF and allows more patients to be treated with RF with curative intent.

Adult↗
PubMed2004

Could immunosuppressive drugs reduce recurrence rate after second resection for Crohn disease?

BACKGROUND: The aim of this study was to assess the possible benefit of postoperative immunosuppressive drugs administration (ie, azathioprine, 6-mercaptopurine, or methotrexate) on long-term surgical recurrence rate after second anastomotic ileocolonic resection. METHODS: From 1984 to 2000, 26 patients with CD underwent second resection for ileocolonic anastomotic recurrence. There were 14 women and 12 men (mean age +/- SD: 34 +/- 9 years). Two groups of patients were compared according to the postoperative treatment: immunosuppressive (IS) drugs group was composed of 14 patients, and control group was composed of 12 patients receiving either salicylates (n = 5) or no treatment (n = 7). RESULTS: Clinical recurrence rate at 3 years was significantly lower in the IS group than in the control group (3/12, 25% vs 6/10, 60%; P < 0.05). Although not significant, after a mean follow-up of 80 +/- 46 months (extr. 17-178 months) after the second resection, clinical recurrence rate at follow-up was also lower in IS group (6/14, 43%) than in control group (9/12, 75%). The mean delay of recurrence was similar in both groups (27 +/- 13 months vs 28 +/- 21; NS). A third intestinal resection was performed less frequently in the IS group than in control group (2/14, 17% vs 7/12, 58%; P < 0.02). CONCLUSIONS: In patients treated with IS drugs, the rate of postoperative recurrence after second ileocolonic CD resection is lower than in untreated patients. Our results suggest that IS drugs should be evaluated prospectively for prevention of second postoperative CD recurrence.

Adult↗