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Biomedical subjects

M Lise

Publications and source records attributed to M Lise.

At least 37 records · Page 2Linked to original sources

Fas ligand is up-regulated during the colorectal adenoma-carcinoma sequence.

AIMS: Fas ligand (FasL) expression by cancer cells may mediate tumour immune privilege. The purpose of the present study was to investigate the timing and significance of FasL expression during the colorectal adenoma-carcinoma sequence. METHODS: FasL expression was studied by immunohistochemistry in 170 formalin-fixed tissue sections representing the entire colorectal adenoma-carcinoma sequence. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to search for FasL mRNA. Analysis of survival was performed in patients with carcinomas. RESULTS: A significant positive linear correlation was found between FasL expression and tumour progression throughout the colorectal adenoma-carcinoma sequence (r(s)=0.677 P<0.001). A pattern of high FasL expression was detected in 19% of high grade adenomas, 40% of stage I-II, 67% of stage III and 70% of stage IV carcinomas. No significant differences were observed between FasL expression in the primary tumours and that in the corresponding liver metastases. The specificity of FasL expression was confirmed at RT-PCR. For stage I-II carcinomas, the 5 year survival was 90% in patients without, or with moderate, tumoural FasL expression compared with 60% in those with high tumoural FasL expression (P<0.05). CONCLUSIONS: Our findings suggest that FasL expression may be involved in the development of colorectal cancer and its progression.

Adenocarcinoma↗

Stop-flow technique for loco-regional delivery of antiblastic agents: literature review and personal experience.

AIMS: The therapeutic approach for primary or recurrent advanced solid tumours, particularly when unresectable, is still one of the main medical challenges in the management of cancer patients. The stop-flow (SF) technique has been recently proposed as a semi-invasive drug delivery system based on the blood supply blockage of the tumour-bearing area. Here, we discuss the principles underlying the SF technique as well as the worldwide experience published so far. We also report on the results of our pilot study on pelvic and limb SF perfusion. METHODS: We reviewed the worldwide experience on SF as reported by the literature published on PubMed from 1990 through 2001. In our series, we treated 20 patients affected with locally advanced melanoma, soft tissue sarcoma or colorectal cancer. RESULTS: This therapeutic modality - at least for some tumours - can achieve encouraging results in terms of clinical response even after conventional therapies have failed. Moreover, as a safe and relatively simple procedure, SF can be applied to patients for whom traditional treatments (i.e. surgery, systemic chemotherapy) are contraindicated because of poor general conditions. CONCLUSIONS: At present, the SF technique should be considered an investigational approach to locally advanced cancers. The encouraging results obtained with this procedure should be validated by large phase III trials.

Antineoplastic Agents↗

Laparoscopic banding: selection and technique in 830 patients.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) with the Lap-Band has been our first choice operation for morbid obesity since September 1993. Results in terms of complications and weight loss are analyzed. METHODS: 830 consecutive patients (F 77.9%) underwent LAGB. Initial body weight was 127.9 +/- SD 23.9 kg, and body mass index (BMI) was 46.4 +/- 7.2 kg/m2. Mean age was 37.9 (15-65). Steps in LAGB were: 1) establishment of reference points for dissection (equator of the balloon inflated with 25 cc air and left crus); 2) creation of a retrogastric tunnel above the bursa omentalis; 3) creation of "virtual" pouch; 4) embedding the band. RESULTS: Mortality was 0, conversion 2.7%, and follow-up 97%. Major complications requiring reoperation developed in 3.9% (36 patients). Early complications were 1 gastric perforation (requiring band removal) and 1 gastric slippage (requiring repositioning). Late complications included 17 stomach slippages (treated by band repositioning in 12 and band removal in 5), 9 malpositions (all treated by band repositioning), 4 gastric erosions by the band (all treated by band removal), 3 psychological intolerance (requiring band removal), and 1 HIV positive (band removed). A minor complication requiring reoperation in 91 patients (11%) was reservoir leakage. 20% of patients who had % excess weight loss < 30 had lost compliance to dietetic, psychological and surgical advice. BMI declined significantly from the initial 46.4 +/- 7.2 to 37.3 +/- 6.8 at 1 year, 36.4 +/- 6.9 at 2 years, 36.8 +/- 7.0 at 3 years, and 36.4 +/- 7.8 at 5 years. CONCLUSION: LAGB is a relatively safe and effective procedure.

Adolescent↗

Prevention of postsurgical adhesions with an autocrosslinked hyaluronan derivative gel.

BACKGROUND: ACP gel is a new crosslinked derivative of hyaluronic acid (HA) that displays the biocompatibility properties of its original polymer but has a higher viscosity. It has been demonstrated in an animal model that the gel reduces adhesions after gynecological surgery. The aim of the present study was therefore to investigate the efficacy of ACP gel in increasing viscosity for the prevention of adhesions after abdominal surgery. METHODS: The antiadhesive effect of ACP gel was tested in a controlled randomized study using a standardized animal model of abdominal surgery involving the creation of defects in the parietal peritoneum and muscular fascia and cecal abrasion. The animals (100 female New Zealand white rabbits) were randomly allocated into five treatment groups to receive: ACP gel (1, 2, 4, and 6%) on the injured area or no ACP gel (control). The incidence of adhesions and their grade (score 0-11) were blindly evaluated 10 weeks after surgery. RESULTS: The percentages of adhesion-free animals were 60, 84, 90, and 84% in the 1, 2, 4, and 6% ACP gel concentration groups, respectively, versus 15% in the control group (P = 0.001). The mean adhesion scores were 3.00 +/- 0.91, 1.37 +/- 0.75, 0.65 +/- 0.45, and 1.16 +/- 0.64 in the 1, 2, 4, and 6% ACP gel groups, respectively, versus 7.70 +/- 0.83 in the control group (P < 0.001). CONCLUSION: ACP gel prevents postsurgical abdominal adhesions even at a 1% concentration. This finding may be of clinical importance in situations in which large volumes of antiadhesive solution are required.

Abdomen↗

Short-term sacral nerve stimulation for functional anorectal and urinary disturbances: results in 40 patients: evaluation of a new option for anorectal functional disorders.

PURPOSE: There are several options in the treatment of fecal incontinence; it is often difficult to choose the most appropriate, adequate treatment. The consolidated experience gained in the urologic field suggests that sacral nerve stimulation may be a further option in the choice of treatment. The aim of our study was to evaluate the preliminary results of the peripheral nerve evaluation test obtained in a multicenter collaborative study on patients with defecatory and urinary disturbances. METHODS: Forty patients (9 males; mean age, 50.2; range, 26-79 years) underwent the peripheral nerve evaluation test, 28 (70 percent) for fecal incontinence and 12 (30 percent) for chronic constipation. Fourteen (35 percent) patients also had urinary incontinence; six had urge incontinence, two had stress incontinence, and six had retention incontinence. Associated diseases were scleroderma (2 patients), spinal injuries (4 patients), and syringomyelia (1 patient). All the patients underwent preliminary investigations with anorectal manometry, pudendal nerve terminal motor latency testing, anal ultrasound, defecography, and if required, urodynamic tests. The electrode for sacral nerve stimulation was positioned percutaneously under local anesthesia in the S2 (4), S3 (34), or S4 (1) foramen unilaterally (1 patient not accounted for because of no response to acute test), based on the best motor and subjective responses of paresthesia of the pelvic floor. Stimulation parameters were average amplitude, 2.8 (range, 1-6) V and average frequency, 15 to 25 Hz. RESULTS: The mean duration of the tests was 9.9 (range, 7-30) days; tests lasting fewer than seven days were not evaluated. There were four early displacements of the electrode. In 22 of the 25 evaluable patients with fecal incontinence, there was an improvement of symptoms (88 percent), and 11 (44 percent) were completely continent to liquid or solid stools, whereas in 7 symptoms were unchanged. Mean number of episodes of liquid or solid stool incontinence per week was 8.1 (range, 4-18) in the prestimulation period and 1.7 (range, 0-12) during the peripheral nerve evaluation test. (P = 0.001; Wilcoxon's signed-rank test). The most important manometric findings were: increase of maximum rest pressure (39.4 +/- 7.3 vs. 54.3 +/- 8.5 mmHg; P = 0.014, Wilcoxon's test) and maximum squeeze pressure (84.7 +/- 8.8 vs. 99.5 +/- 1.1 mmHg; P = 0.047), reduction of initial threshold (63.6 +/- 5.2 vs. 42.4 +/- 4.7 ml; P = 0.041) and urge sensation (123.8 +/- 0.6 vs. 78.3 +/- 8.9 ml; P = 0.05). An improvement was also found in patients with constipation, with reduction in difficulty emptying the rectum, with prestimulation at 7 (range, 2-21) episodes per week and end of peripheral nerve evaluation test at 2.1 (range, 0-6) episodes per week, P < 0.01) and in the number of unsuccessful visits to the toilet, which dropped from 29.2 (7-24) to 6.7 (0-28) per week (P = 0.01). The most important manometric findings in constipated patients were an increase in amplitude of maximum squeeze pressure during sacral nerve stimulation (prestimulation, 63 +/- 0 mm Hg; end of peripheral nerve evaluation test, 78 +/- 1 mm Hg; P = 0.009) and a reduction in rectal volume for urge threshold (prestimulation, 189 +/- 52 ml; end of peripheral nerve evaluation test, 139 +/- 45 ml; P = 0.004). CONCLUSIONS: In functional bowel disorders short-term sacral nerve stimulation seems to be a useful diagnostic tool to assess patients for a minor invasive therapy alternative to conventional surgical procedure.

Adult↗

Patterns of recurrence after resection of colorectal liver metastases: prediction by models of outcome analysis.

Various series have reported similar survival and recurrence rates after resection of colorectal liver metastases (CRLM). If outcomes were predictable, indications for surgery could be improved. This hypothesis was tested in 135 consecutive patients with CRLM who underwent "curative" resection from 1977 to 1997. Among the 132 patients available for follow-up, three groups were identified on the basis of outcome: (1) survival of more than 5 years disease-free (n = 32; 24%); (2) diffuse recurrences within the first 6 months (n = 24; 18%); and (3) discrete recurrences for which reresection was performed (n = 16; 12%). As our results are similar to those reported in the literature, we assumed that about 50% of patients with resectable lesions have recognizable patterns of recurrence. At multivariate analysis, factors significant for disease-free survival (DFS) were the percentage of liver invasion, metastases to lymph nodes at the primary site, number of metastases, preoperative glutamic pyruvic transaminase (GPT) level, and type of liver resection. On the basis of the relative risk (RR) expressed by significant prognostic factors, a score model was developed, and three prognostic groups were defined: Group A, with the best prognostic score, included 23 of 32 (72%) patients who survived more than 5 years, and that with the worst prognostic score (group C) included 22 of 24 (92%) patients with early diffuse recurrences. Extreme (especially unfavorable) outcomes can therefore be predicted. By using improved models of outcome analysis, many patients could be spared surgery as first-line treatment, and stratification criteria could be worked out for future trials.

Adenocarcinoma↗

P27kip1 expression is associated with tumor response to preoperative chemoradiotherapy in rectal cancer.

BACKGROUND: Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression. METHODS: Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response). RESULTS: The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy. CONCLUSIONS: Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.

Adult↗

Colorectal cancer metastatic phenotype stimulates production by fibroblasts of N-terminal peptide of type III collagen: clinical implications for prognosis.

In this study we assessed whether the serum levels of the N-terminal peptide of type III collagen (PIIIP), an index of type III collagen synthesis, are influenced by colorectal cancer stage, and whether "in vitro" fibroblast growth and PIIIP production could be altered by tumor tissues obtained from metastatic and nonmetastatic colorectal cancer. 208 colorectal cancer patients (115 colon and 93 rectum) were studied; 54 were stage I, 62 stage II, 37 stage III and 55 stage IV. PIIIP serum levels were significantly higher in stage IV as compared to all other patient groups. The 5-year survival of stage I, stage II, stage III and stage IV patients were 87%, 88%, 32% and 20%, respectively. In the subgroup of stage I and stage II patients considered together, PIIIP (> 0.5 U/ml), but not CEA (> 5 microg/l) serum levels, were predictive for survival. Fibroblast growth was significantly inhibited, while PIIIP production was significantly enhanced, when these cells were conditioned with colorectal cancer homogenates obtained from patients with distant metastases, than from those without distant metastases. In conclusion, colorectal tumors, when metastatic, stimulate fibroblasts' PIIIP synthesis and the serum levels of this peptide might predict patients' outcome after radical surgery.

Carcinoembryonic Antigen↗

Multimodal treatment of peritoneal carcinomatosis and sarcomatosis.

Peritoneal carcinomatosis and sarcomatosis (PCS) are short-term fatal conditions amenable only to palliative treatment. They are generally considered as a systemic disease at clinical presentation, and are resistant to standard treatments. However, there may be in the natural history a phase of loco-regional tumour spread during which the tumour may still be curable. Surgical treatment alone, or in combination with systemic chemotherapy, has yielded poor results in terms of survival and quality of life. One approach is cytoreductive surgery (CS) combined with the intraperitoneal administration of antiblastic agents. This may diminish any residual tumour following macroscopic excision and may overcome the pharmacokinetic limits of systemic chemotherapy. A further improvement in this multimodal approach may be achieved by the use of hyperthermic intraperitoneal intraoperative chemotherapy (HIIC). Results so far have been encouraging. However, series reported in the literature are relatively small and heterogeneous, and clinical and technical factors which include the selection of patients, optimal drugs dosage and temperature, evaluation of outcome and costs are still under discussion.

Antineoplastic Agents↗

Protein profiles in sera of patients with malignant cutaneous melanoma.

Seventeen samples of sera from patients with malignant cutaneous melanoma at various stages and 14 samples from healthy subjects were analysed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Results highlighted the presence of several protein species at molecular weights lower than 30000 Da, presumably originating from proteolysis, in the sera of the patients with melanoma. These species were completely absent in healthy subjects. In particular, the presence and abundance of species with molecular weights in the range 2500-3500 Da exhibit significant variations related to the different clinical stages of the disease.

Blood Proteins↗

Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer.

BACKGROUND: Interleukin-6 (IL-6) is an important proinflammatory cytokine that has multiple effects on stimulating inflammation and cell growth. Experimental data suggest that carcinoembryonic antigen (CEA) induces the systemic production of IL-6 and that IL-6 may stimulate tumor cell growth at metastatic sites. We tested the hypothesis that blood concentrations of IL-6 are associated with the amount of circulating CEA and with prognosis in patients with colorectal cancer. METHODS: CEA and IL-6 concentrations were measured by using enzyme immunoassay in preoperative serum samples from 208 patients with stages I through IV colorectal cancer. RESULTS: Linear regression analysis showed a significant association between serum values of CEA and IL-6 (r = .544; R2 = .296; P < .001). Patients with stage III and stage IV disease had a significantly higher IL-6 serum concentration than those with stage I and stage II disease. In patients with stages I through III, 5-year survival was 83% in cases with concentrations of IL-6 at 10 pg/ml or less (n = 94) and 56% in cases with IL-6 concentrations of more than 10 pg/ml (n = 54; P = .001; median follow-up time, 46 months). By using multivariate analysis, an IL-6 concentration of more than 10 pg/ml was an independent prognostic factor of survival (relative risk = 1.820; P = .020). CONCLUSIONS: In patients with colorectal cancer, blood concentration of IL-6 is associated with high circulating CEA and advanced stage. Furthermore, an IL-6 concentration of more than 10 pg/ml is an independent negative prognostic marker of survival.

Adult↗

Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations.

1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29-23.51) and 3.09 (1.03-10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedure's completion.

Adolescent↗

Influence of age and menopausal status on pathologic and biologic features of breast cancer.

The distribution of the main prognostic factors in different age groups was evaluated in 1226 patients operated on for primary breast cancer, in order to identify those influenced by age and/or menopausal status. Patients were divided into the following groups: 1) 40 years of age and under; 2) premenopausal over 40 years of age; 3) postmenopausal under 75 years of age and 4) 75 years of age and over. Our findings showed that the youngest patients had the worst prognostic pattern, which improves as age increases and is the best in patients over 75 years of age. Some of the parameters investigated (tumour size, histologic and nuclear grade, tumour infiltrating lymphocytes, p53 and Ki 67) were found to be influenced by age, some (necrosis and oestrogen receptors) were influenced by menopausal status and/or age, some (vascular invasion, ploidy, S-phase and progesterone receptors) showed significant differences in different age groups but there was no consistent relation with patient age or menopausal status, and others (node status, ErbB2/Neu and Cathepsin D) were not influenced by age or menopause.

Journal Article↗

Sentinel node biopsy in breast cancer.

Axillary lymph node dissection (ALND) is an important tool in staging patients with breast cancer. However, this procedure has several sequelae and complications and improvement in early diagnosis has led to an increasing number of cases of ALND in which axillary nodes are found to be negative. Sentinel node (SN) biopsy appears to be a less invasive alternative to ALND. The aim of the present study was to assess whether SN is a reliable indicator for axillary staging. We studied 126 consecutive patients with T1-T2 breast cancer and clinically negative axilla. In each case, 30-70 MBq of 99mTC-labelled colloidal albumin was injected subdermally close to the tumour and SN was visualised by lymphoscintigraphy. Surgery was performed 24 h after injection and the SN was removed under the guidance of a gamma ray-detecting probe. ALND was then undertaken in all cases. A histopathologic examination of the SNs was then made and the findings compared with the status of the other axillary nodes. SNs were identified and biopsied in 115/126 patients (91.3%) and correctly predicted the axillary status in 110/115 cases (95.6%). In five cases (4.4%), SNs were found to be negative, but other axillary nodes were positive. Our data confirm that SN biopsy is a good method for staging the axilla in patients with breast cancer. However, before SN biopsy can replace ALND in daily clinical practice, some technical aspects must be standardized, and clinical trials are required in order to clarify the prognostic impact of false-negative cases.

Journal Article↗

Clinical correlations of alpha2,6-sialyltransferase expression in colorectal cancer patients.

We have previously demonstrated a link between alpha2,6-Sialyltransferase (alpha2,6-ST; E.C. 2.4.99.1) expression and differentiation of colon tumors. So far, information is not available relative to the expression of alpha2,6-ST in tumors and the survival of patients with colorectal cancer. We have examined the expression of alpha2,6-ST in a variety of colorectal adenocarcinomas (n = 46) at different stages of differentiation (G1 to G3) by immunoperoxidase assay using monoclonal antibody (MAb) 6B9. Clinical outcome of the patients in a 5-year follow-up study has been correlated with the expression of alpha2,6-ST in tumors surgically removed from the same patients. No significant difference in the alpha2,6-ST expression was noted when age, sex, and tumor locations (colon, rectum) were included as parameters. However, 52% of the moderate (G2) and well-differentiated (G1) adenocarcinomas showed stronger alpha2,6-ST expression compared with poorly differentiated (G3) adenocarcinomas. Notably, absence to moderate levels of tumor alpha2,6-ST expression was correlated with 100% survival in patients with stage I and II tumors compared with 64% survival in patients with strong tumor alpha2,6-ST expression (p < 0.01). These studies suggest a negative correlation between the expression of alpha2,6-ST in tumors and a good clinical outcome in colorectal cancer patients.

Adenocarcinoma↗

Variation in lipid levels in morbidly obese patients operated with the LAP-BAND adjustable gastric banding system: effects of different levels of weight loss.

BACKGROUND: A moderate weight loss is known to improve the lipid levels in simple obesity. The extent of weight loss needed to achieve a clinically meaningful effect on lipid abnormalities in morbid obesity is little understood. We analyzed the effects of different levels of body weight loss on the lipid levels of morbidly obese patients operated with the LAP-BAND System. METHODS: 225 morbidly obese patients (172 F and 53 M) in which a complete lipid profile has been collected both before and 12-18 months after surgery were studied. The changes of the lipid profile were analyzed according to different levels of percent weight loss (%WL: <10%, 10-20%, 20-30%, >30%). RESULTS: Mean weight loss was 30.7+/-15.2 kg, corresponding to a 23.1+/-9.7% reduction of body weight. A large variability in the weight loss was observed. A significant difference in the change of the lipid parameters between the group with <10%WL and the group with 10-20%WL was observed for total-cholesterol (+10.0+/-17.2% vs -0.7+/-14.7%; p<0.05), for the LDL (+18.7+/-26.3% vs +3.1+/-22.9%; p<0.05), and for the triglycerides (+7.7+/-26.3% vs -21.9+/-25.4%; p<0.05). No further significant differences were found between the two groups with greater weight loss (20-30%WL and >30%WL) and the group with 10-20%WL, the only exception being the percent change in triglycerides levels, i.e. higher in the group with %WL >30 (-33.6+/-31.5% vs -21.9+/-25.4%; p<0.05). CONCLUSION: A moderate weight loss of 10-20% of initial body weight produced the maximal effects on the lipid levels in morbid obesity.

Adult↗

Early detection of melanoma: an educational campaign in Padova, Italy.

To evaluate a public campaign for the early referral and treatment of cutaneous melanoma, an educational programme based on self-selection by subjects was organized in Padova, Italy in 1991. In the period from 1991 to 1996, 90,000 leaflets containing information on naevi, melanoma and skin self-examination were mailed to each household, reaching a population of 243,000 subjects. A total of 2050 individuals requested a skin check as a result of the leaflet. Most were at low risk, the majority being female (68%) and aged under 40 years (51.6%), with no risk factors (58.3%). One hundred and ninety subjects were referred for surgery for pigmented and non-pigmented suspect lesions. Histological diagnoses, obtained for all lesions, comprised 13 melanomas, 17 dysplastic naevi, 17 basocellular carcinomas, 140 pigmented benign lesions and three lesions of other types. The percentage of thin melanomas (< 1.50 mm) was 92.3%. Three hundred and fifty patients considered at risk at the first skin examination attended regular follow-up examinations. The sensitivity and predictive positive value of the visual examination were 92.8% and 6.8%, respectively. The impact of this campaign was evaluated in the Local Health District of Padova, comparing data from the pre-campaign period (1987-1990) with those from the campaign period (1991-1996); a trend towards a lower stage was observed (mean thickness 2.0 mm versus 1.50 mm; P < 0.02).

Adult↗

Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusion.

BACKGROUND: Of the different options for limb-sparing treatment for patients with soft tissue limb sarcomas (STLS), hyperthermic antiblastic perfusion (HAP) combined with surgery might be the most effective in terms of tumor resectability, local control, and aesthetic and functional results. The aim of this study was to identify the most safe, active, and effective perfusional regimen in order to improve multidisciplinary treatment for patients with advanced STLS. METHODS: The first trial undertaken (which involved 18 patients) was a Phase I study to assess the maximum tolerable dose of doxorubicin, the second (with 29 patients) was a Phase II study of HAP with doxorubicin, and the third (with 20 patients) was a Phase I-II study to assess the maximum tolerable dose and tumor response to doxorubicin combined with tumor necrosis factor (TNF). Statistical tests were performed on the whole series to evaluate the factors influencing local toxicity, tumor response, and local disease free and overall survival. RESULTS: Grade IV systemic toxicity was observed in only 2 cases (TNF >1 mg). Muscle temperature (>41.5 degrees C) was the limiting factor for locoregional toxicity. Limb-sparing surgery was feasible for 60 patients (92.3%). The highest tumor response was observed in the third trial, with complete histologic necrosis in 26.3% of cases. Muscle and tumor temperature (>41.5 degrees C) and the type of trial had a statistically significant influence on response. The local recurrence rate was influenced by tumor site, type of trial, maximum tumor temperature, and local toxicity, whereas the overall survival was influenced by the presence of metastasis, tumor grade, and response to treatment. CONCLUSIONS: These findings show that HAP with doxorubicin and TNF (< or =1 mg) at a muscle temperature of < or =41.5 degrees C is a safe, active, and effective perfusional regimen for the multidisciplinary treatment of patients with advanced STLS.

Adult↗