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Biomedical subjects

M Lise

Publications and source records attributed to M Lise.

At least 19 recordsLinked to original sources
PubMed2005

Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and the ICCG.

BACKGROUND: In patients who underwent radical resection for gastric cancer, we investigate the relative efficacy of combined 5-fluorouracil+adriamycin or epirubicin and methotrexate with leucovorin rescue (FAMTX or FEMTX) compared with a control arm. PATIENTS AND METHODS: This report is a prospective combined analysis of two randomized clinical trials conducted on patients who underwent radical resection for histologically proven adenocarcinoma of the stomach or esophago-gastric junction. Three hundred and ninety-seven untreated patients, 206 from 23 European Organization for Research and Treatment of Cancer (EORTC) institutions and 191 from 16 International Collaborative Cancer Group (ICCG) institutions, were randomized. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the treatments were compared for these end-points by means of the log-rank test, retrospectively stratified by trial. RESULTS: In a planned combined analysis of the two trials, no significant differences were found between the treatment and control arms for either DFS (hazards ratio: 0.98, P=0.87) or OS (hazards ratio: 0.98, P=0.86). The 5-year OS was 43% in the treatment arm and 44% in the control arm and the 5-year DFS was 41% and 42%, respectively. CONCLUSION: Neither FAMTX nor FEMTX can be advocated as adjuvant treatment in patients who undergo resection for gastric cancer.

Adenocarcinoma↗
PubMed2005

A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer.

BACKGROUND: Oxaliplatin (OXA) significantly enhanced the antitumour activity of 5-fluorouracil (FUra) in patients with advanced colorectal cancer and displayed radiosensitising properties in preclinical studies. This study was thus performed to test the feasibility, identify the recommended doses (RDs) and explore preliminarily the clinical activity of weekly OXA and infused FUra combined with preoperative pelvic radiotherapy. PATIENTS AND METHODS: Forty-six patients with recurrent or locally advanced (cT3-4 and/or N+) adenocarcinomas of the mid-low rectum were treated with escalating doses of OXA (25, 35, 45, 60 mg/m2, weekly for 6 weeks) and FUra (200-225 mg/m2/day, 6-week infusion) concurrent to preoperative pelvic radiotherapy (50.4 Gy/28 fractions). The RDs for the phase II part of the study were immediately below the level resulting in dose-limiting toxicities in more than one third of the patients, or corresponded to the last planned dose level. RESULTS: In the escalation phase, dose-limiting toxicities only occurred in one patient at the fourth level and one of six patients treated at the last planned dose level (grade III diarrhoea). OXA 60 mg/m2 and FUra 225 mg/m2/day are therefore the RDs for the regimen. Among 25 patients globally treated at these doses (phase II part), the incidence of grade III diarrhoea was 16% with no grade IV toxicity. Neurotoxicity did not exceed grade II (12%). All patients completed radiotherapy and were operated on as scheduled. Twenty-one of 25 patients had the tumour down-staged after chemoradiation with seven (28%) pathological complete responses and 12 (48%) residual tumours limited to ypT1-2N0. CONCLUSIONS: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.

Adult↗
PubMed2005

Axillary recurrence after negative sentinel lymph node biopsy without axillary dissection: a study on 479 breast cancer patients.

AIMS: To determine the axillary recurrence rate in breast cancer patients with negative sentinel lymph nodes (SLN) who did not undergo further axillary lymph node dissection (ALND), and to establish whether this conservative axillary approach leads to an increased recourse to diagnostic axillary biopsy during the follow-up period because of the clinical suspicion of nodal recurrence. METHODS: In 479 patients, operated on for early breast cancer between 1998 and 2002 in five institutions, SLN biopsy was negative and no further axillary surgery was performed. SLN was localized using subdermal injection with 30-50 MBq of 99m-Tc-colloidal albumin. Follow-up controls were performed at 6-monthly intervals. RESULTS: The mean number of SLNs removed was 1.4 per patient. Most patients (90.6%) were given adjuvant systemic therapy, based on the primary tumour characteristics. At a median follow-up of 35.8 months, no clinical axillary recurrence was found. No patient underwent surgical axillary biopsy for suspicious clinical or ultrasonographic findings. CONCLUSIONS: Our results confirm that SLN biopsy without ALND in SLN-negative patients with early breast cancer is not followed by clinically evident axillary recurrence in the short-term.

Adult↗
PubMed2005

Extended lymphadenectomy (D2) in patients with early gastric cancer.

AIMS: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. METHODS: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. RESULTS: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). CONCLUSIONS: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed.

Adenocarcinoma↗
PubMed2004

Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma.

Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.

Adult↗
PubMed2004

Curative surgery for obstruction from primary left colorectal carcinoma: primary or staged resection?

BACKGROUND: In 8 to 29% of patients with colorectal carcinoma, obstruction is the main symptom at diagnosis, and 85% of patients undergoing emergency colorectal surgery have obstruction from colorectal carcinoma. The prognosis of patients who undergo emergency surgery for obstruction is often poor. So far, two types of surgical approach have been used for this condition: primary resection (primary anastomosis or Hartmann's procedure) with simultaneous treatment of carcinoma and obstruction, or staged resection (treatment of the obstruction prior to resection).However, neither strategy has been found to have any advantages over the other. OBJECTIVES: To ascertain whether primary resection in patients with obstruction from left colorectal carcinoma has advantages over staged resection in terms of morbidity and mortality. SEARCH STRATEGY: Electronic database searches of Cochrane Controlled Trials Register, Medline, Cancerlit, Embase. Hand searching of the most important journals in the fields of oncology and surgery from 2003 and onward until the time of writing. SELECTION CRITERIA: Randomised Clinical Trials (RCT) and Controlled Clinical Trials (CCT), in which a group of patients who undergo primary resection for intestinal obstruction from left primary colorectal carcinoma is compared with a group of patients who undergo staged resection for the same condition. Since only one study of this type was available, we considered all other studies, except for case-controls, on the basis of the best possible available evidence. Studies were considered without language restrictions. DATA COLLECTION AND ANALYSIS: Two reviewers (GLDS, CG) examined all the citations and abstracts derived from the electronic search strategy. Reports of potentially relevant trials were retrieved in full. Both reviewers independently applied the selection criteria to trials reports. Reviewers were not blind to the names of institutions, journals or authors of trials. A third opinion (SP, ML) was obtained to resolve disagreements. MAIN RESULTS: We identified 2043 citations: Medline 1205, Embase 635, Cancerlit 203. One study for potential inclusion was identified, but was then excluded (Kronborg 1995). REVIEWERS' CONCLUSIONS: The limited number of identified trials together with their methodological weaknesses do not allow a reliable assessment of the role of either therapeutic strategy in the treatment of patients with bowel obstruction from colorectal carcinoma. It would appear advisable to conduct high quality large scale RCT to establish which treatment is more effective. However, it is doubtful whether they could be carried out in a timely and satisfactory way in this particular surgical context.

Colorectal Neoplasms↗
PubMed2004

IL-10 stimulatory effects on human NK cells explored by gene profile analysis.

The molecular mechanisms underlying the increase of natural killer (NK) cell anticancer activity mediated by interleukin (IL)-10 have not been elucidated. The aim of this study was to identify potential molecular mediators of IL-10 stimulatory effects by exploring the NK cell gene display induced by this cytokine. Gene profile was determined by high-throughput cDNA microarray and quantitative real-time PCR. In vitro, NK cells resting or conditioned with IL-10 were tested for cytotoxicity, migration and proliferation. IL-10 enhanced mRNA levels of cell activation/cytotoxicity-related genes (eg secretogranin, TIA-1, HMG-1, interferon-inducible genes) not upregulated by IL-2. In line with these findings, IL-10 increased NK cell in vitro cytotoxicity against Daudi cells. Unlike IL-2, IL-10 did not show any significant effect on NK cell in vitro proliferation and migration. However, gene profile analysis showed that IL-10 increased the expression of cell migration-related genes (eg L-selectin, vascular endothelium growth factor receptor-1, plasminogen activator, tissue; formyl peptide receptor, lipoxin A4 receptor), which might support a stimulatory effect not evident with the in vitro functional assay. Overall, gene profiling allowed us to formulate new hypotheses regarding the molecular pathways underlying the stimulatory effects of IL-10 on NK cells, supporting further investigation aimed at defining its role in cancer immune rejection.

Cell Movement↗
PubMed2004

Hyperthermic isolated liver perfusion for unresectable liver cancers: pilot study.

Isolated hepatic perfusion (IHP) is a recently reconsidered locoregional approach for unresectable primary or metastatic cancer and encouraging results have been achieved from its clinical application. Ten patients underwent hyperthermic IHP with melphalan. There was no intraoperative mortality. In the postoperative period two patients died due to multi-organ failure. Four patients had significant but transient hepatic toxicity. In 8 assessable patients, the overall response rate was 63%. We observed objective tumor regression in a significant percentage of patients refractory to standard treatments. Locoregional toxicity was significant, which underscores the need for a more accurate preoperative evaluation of hepatic function.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed2004

Hyperthermic isolated perfusion with low-dose TNFalpha and doxorubicin in patients with locally advanced soft tissue limb sarcomas.

We report here the results of 27 patients who underwent hyperthermic isolated limb perfusion with low-dose TNFalpha (1 mg) and doxorubicin (8.5 mg/l of limb volume) for locally advanced soft tissue sarcomas. A tumor response was observed in 85% of cases. After a median follow-up of 30 months, limb salvage and local disease control were achieved in 82 and 85% of patients, respectively. Locoregional toxicity was low or mild in 14 patients, while 2 patients had severe limb toxicity. Systemic side effects were negligible. The perfusate/plasma area under the curve (AUC) ratio for TNFalpha was 56. HILP with low-dose TNFalpha and DXR proved to be an active neoadjuvant drug regimen against limb-threatening STS.

Adult↗
PubMed2004

Hypoxic antiblastic stop-flow perfusion: clinical outcome and pharmacokinetic findings.

Stop-flow perfusion (SFP) is a recently implemented locoregional treatment based on the vascular isolation of the tumor bearing body district through a radiointerventistic technique. SFP is currently under investigation as a palliative therapeutic option for patients with locally advanced tumors. This paper reports on the results of our prospective study of limb and pelvic SFP. Thirty-seven patients were treated with SFP. No postoperative deaths occurred. Locoregional and systemic toxicity were observed after 22 and 31 treatments, respectively; complete and partial response after 3 (6%) and 24 (51%) SFPs, respectively. The pharmacokinetic study showed that pelvic SFP was associated with a leakage rate higher than femoral SFP (38% vs 28%). In conclusion, SFP is a feasible procedure. Toxicity and tumor response rates strictly depend upon drug leakage control.

Adult↗
PubMed2003

Effect of antiadhesive agents on peritoneal carcinomatosis in an experimental model.

BACKGROUND: Auto-crosslinked polysaccharide hyaluronan-based solution (Hyalobarrier-gel) prevents postoperative adhesions. However, its effect on tumour growth is still unknown. The aim of the present study was therefore to investigate the impact on survival of intra-abdominally administered Hyalobarrier-gel, native hyaluronan (HA) and hyaluronan/carboxymethylcellulose (HA/CMC), after intraperitoneal tumour implantation. METHODS: After receiving an intraperitoneal inoculum of the human HT29 colorectal cell line, 615 athymic nude mice were assigned randomly to five groups: groups 1 and 2 received Hyalobarrier-gel 20 mg/ml (n = 124) and 40 mg/ml (n = 126) respectively; groups 3 and 4 received HA (n = 120) and HA/CMC film (Seprafilm) (n = 123) respectively. The survival of each treated group was compared with that of group 5, the control, which had no treatment (n = 122). RESULTS: As 34 of the 615 mice were not eligible, 581 animals were considered for the analysis. At 120 days, 136 animals (23.4 per cent) were still alive. At autopsy there was macroscopic absence of tumour in 75 cases (12.9 per cent). No statistically significant differences were found between the treatment and the control groups with respect to postoperative death and absence of tumour implantation. There was no difference in survival rate between the control group and groups treated with Hyalobarrier-gel, HA or HA/CMC. CONCLUSION: Hyalobarrier-gel, HA and HA/CMC had no negative impact on the survival rate in mice that received an intraperitoneal implantation of HT29 colorectal human tumour cells.

Animals↗
PubMed2003

Phase I-II study on isolation antiblastic fotemustine perfusion after dacarbazine chemosensitization for advanced melanoma of the extremities.

Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.

Adult↗
PubMed2003

TNF-based limb perfusion for cutaneous melanoma in transit metastases: suggestions for modification of the perfusional schedule.

Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patients with extensive in-transit disease, and L-PAM, combined or not with TNF, represents the most active drug. We here report on our clinical experience with TNF-based limb perfusion. Thirty-seven stage III patients underwent TNF-based limb perfusion, 22 with bulky disease, 15 with recurrences after perfusion with L-PAM. Ten patients were enrolled in a phase I-II study and treated with escalating doses of TNF (0.5-3 mg). The impact of disease burden, temperature, perfusion duration was assessed on tumor response. No postoperative death was observed. No significant systemic toxicity was recorded. Locoregional toxicity was G5 in one patient, G3 in 2, G2 in 9 and G1 in 25. Twenty-four (66%) patients had complete response, 11 (31%) partial and 1 (3%) no change. After a median follow-up of 20 months 14 (38%) patients are NED, 10 (27%) are AWD and 13 (35%) DOD. No significant statistical difference for tumor response were seen for disease burden, ILP temperatures and duration. Our results showed that it is possible to modify the perfusion schedule, without compromising the response rate but with lower cost and toxicity.

Adult↗
PubMed2003

Treatment options for liver metastases from colorectal cancer.

The liver is the most common site of distant metastasis from colorectal cancer. About one-fourth of patients with liver metastases from colorectal cancer have no other sites of metastasis. Surgical resection of colorectal cancer liver metastases can result in a 24%-38% five-year survival. However, only a minority of patients are candidates for resection and no adjuvant treatment has been demonstrated to be effective in increasing the survival rate following radical surgery. For unresectable disease, several treatments have been tested in the clinical setting, although none of them can be currently considered a standard approach. Systemic chemotherapy is not generally considered a treatment for cure, although newer regimens appear to improve median survival. Locoregional therapies such hepatic intra-arterial chemotherapy and isolated hepatic perfusion may be offered to patients with unresectable liver metastases in the absence of extra-hepatic disease. However, the efficacy of these treatments is still being determined. Both systemic and locoregional chemotherapy might be useful in the neoadjuvant setting to increase the resectability of liver metastases initially not amenable to surgical resection.

Adenocarcinoma↗
PubMed2002

Curative surgery for obstruction from primary left colorectal carcinoma: primary or staged resection?

BACKGROUND: In 8 to 29% of patients with colorectal carcinoma, obstruction is the main symptom at diagnosis, and 85% of patients undergoing emergency colorectal surgery have obstruction from colorectal carcinoma. The prognosis of patients who undergo emergency surgery for obstruction is often poor. So far, two types of surgical approach have been used for this condition: primary resection (primary anastomosis or Hartmann's procedure) with simultaneous treatment of carcinoma and obstruction or staged resection (treatment of the obstruction prior to resection). However, neither strategy has been found to have any advantages over the other. OBJECTIVES: To ascertain whether primary resection in patients with obstruction from left colorectal carcinoma has advantages over staged resection in terms of morbidity and mortality. SEARCH STRATEGY: Electronic database searches of Cochrane Controlled Trials Register, Medline, Cancerlit, Embase. Hand searching of the most important journals in the fields of oncology and surgery from the year 2000 until the time of writing. SELECTION CRITERIA: Randomised Clinical Trials (RCT) and Controlled Clinical Trials (CCT), in which a group of patients who undergo primary resection for intestinal obstruction from left primary colorectal carcinoma is compared with a group of patients who undergo staged resection for the same condition. Since only one study of this type was available, we considered all other studies, except for case-controls, on the basis of the best possible available evidence. Studies written in English, French, German and Italian and, where necessary, other languages, were considered. DATA COLLECTION AND ANALYSIS: Two reviewers (GLDS, CG) examined all the citations and abstracts derived from the electronic search strategy. Reports of potentially relevant trials were retrieved in full. Both reviewers independently applied the selection criteria to trials reports. Reviewers were not blind to the names of institutions, journals or authors of trials. A third opinion (SP, ML) was obtained to resolve disagreements. MAIN RESULTS: The electronic database searches yielded a total of 1412 citations: Medline 1026, Embase 386. From these, one study for potential inclusion was identified, but was then excluded. REVIEWER'S CONCLUSIONS: The limited number of identified trials together with their methodological weaknesses do not allow a reliable assessment of the role of either therapeutic strategy in the treatment of patients with bowel obstruction from colorectal carcinoma. It would appear advisable to conduct high quality large scale RCT to establish which treatment is more effective. However, it is doubtful whether they could be carried out in a timely and satisfactory way in this particular surgical context.

Colorectal Neoplasms↗
PubMed2002

Cytokine, infiltrating macrophage and T cell-mediated response to development of primary and secondary human liver cancer.

BACKGROUND: Kupffer cells, monocytes and infiltrating T cells have been considered the major source of interleukin-1beta and tumour necrosis factor-alpha in the liver. AIMS; To explore the expression of interleukin-1beta and tumour necrosis factor-alpha and to evaluate the density and the distribution of T lymphocytes and monocytes/macrophages in the liver of patients with primary and secondary tumours. METHODS: Tumoural and peritumoural liver samples were examined from 21 patients with hepatocellular carcinoma, 10 with hepatic metastases, 5 with benign focal liver lesions and 4 healthy adult livers. Interleukin-1beta and tumour necrosis factor-alpha mRNAs were detected by a semiquantitative comparative reverse transcriptase polymerase chain reaction. T lymphocytes and monocytes/macrophages were detected by immunohistochemistry. RESULTS: Higher levels of interleukin-1beta, tumour necrosis factor-alpha, CD3+ and CD68+ cells were found in the tissue surrounding hepatocellular carcinoma and metastases than in the tumour itself. A strong expression of CD68+ and CD3+ cells was found mainly along the tumour-host interface but the highest expression of CD3+ cells was found at the metastasis interfaces. Interleukin-1beta expression, CD3+ and CD68+ cell densities were higher in peritumoural samples than in so-called "normal" liver tissue. CONCLUSIONS: An increased production of interleukin-1beta and, to a lesser extent, of tumour necrosis factor-alpha mRNA coincides with the presence of cancer be it primary or secondary, both in healthy and cirrhotic livers. The presence of cancer, irrespective of the presence of underlying liver damage, appears to play the most important role.

Adult↗