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Biomedical subjects

D Nitti

Publications and source records attributed to D Nitti.

At least 19 recordsLinked to original sources
PubMed2006

Complications, functional outcome and quality of life after intensive preoperative chemoradiotherapy for rectal cancer.

AIMS: To investigate early and late complications in 44 patients with locally advanced mid-low rectal cancer enrolled in a phase I-II study, who had received an aggressive chemoradiation treatment (50.4Gy/28F; 5-FU continuous infusion and weekly Oxaliplatin) followed by total mesorectal excision and 5-FU based postoperative chemotherapy. The aim of the present study is also to evaluate functional outcome and quality of life (QoL) in a sub-group of 22 patients. METHODS: Standardized forms for early and late surgical complications were completed for all patients. Anorectal function and QoL were also investigated in 22 patients who underwent surgery in the same surgical unit, using the fecal incontinence scoring system (FIS) and EORTC-QLQ-CR38 questionnaires, compiled before and after radiotherapy and at least 8 months after surgery. The differences over time in scores were analyzed using repeated measure ANOVA. RESULTS: The median age of patients (25 males and 19 females) was 58 (range: 34-73) years. A low anterior resection was performed in 39 cases, radical resection in 41, and 12 patients had a pathological complete response. There were no operative deaths; 4 and 9 patients required re-operation for early and late complications, respectively. FIS score did not present a significant worsening over time. According to data in the EORTC-QLQ-CR38 questionnaire, a significant improvement over time was found only for "future perspective". CONCLUSION: Our findings seem to indicate that this aggressive 5-FU-Oxalipaltin-based treatment implies no impairment of QoL and anorectal function, even if a high rate of late major complications was observed. Studies on larger series are required to confirm these results.

Adenocarcinoma↗
PubMed2006

High prevalence of isolated tumour cells in regional lymph nodes from pN0 colorectal cancer.

BACKGROUND: The prevalence of isolated tumour cells (ITCs) in regional lymph nodes from colorectal cancer (CRC) is controversial and has never been prospectively assessed in large groups of consecutive patients. pN0 early-relapsing CRC can be explained by lymph node-ITC. AIM: To assess the prevalence of ITCs in regional lymph nodes from 309 consecutive patients with pN0M0 (pathological (p)-tumour-node-metastasis (TNM) staging system) CRCs. PATIENTS AND METHODS: ITCs were assessed by immunohistochemistry (MNF116 monoclonal antibody (1:100); Dako, Glostrup, Denmark) in two serial histological sections obtained from 5016 mesenteric lymph nodes from 309 patients with pN0 CRCs (mean number of lymph nodes per patient = 16.2; p-TNM stage 0, n = 25; p-TNM stage I, n = 123; and p-TNM stage II (A+B), n = 161). Tumour histology, vascular cancer invasion and pathological stage were also recorded. RESULTS: ITCs were detected in the regional lymph nodes of 156 of 309 (50.5%) patients with CRC, mostly in nodes located within 3 cm from the neoplasia. ITC status correlated with (a) tumour p-TNM stage (Pearson's chi(2): p<0; ordered logistic regression: odds ratio (OR) = 4.6; 95% confidence interval (CI) = 2.88 to 7.33; p<0) and (b) pT value (Pearson's chi(2): p = 0; ordered logistic regression: OR = 4.9; 95% CI = 3.1 to 7.7; p<0). By multivariate analysis, including p-TNM stage, vascular invasion and ITC status, both stage (OR = 5.1; 95% CI = 2.9 to 8.9; p<0) and vascular invasion (OR = 4.2; 95% CI = 1.94 to 8.98; p<0) were found to be independent variables associated with ITC+ lymph nodes. CONCLUSION: More than 50% of pN0-CRC patients have ITCs in the mesenteric lymph nodes. ITC status is significantly correlated with cancer stage and vascular cancer invasion. The clinicopathological effect of ITC remains to be prospectively evaluated.

Adenocarcinoma↗
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

Axillary sentinel lymph nodes in breast cancer: a single lymphatic pathway drains the entire mammary gland.

AIM: To report the pattern of lymphatic mapping following intrasubdermal injections of radiocolloid and of blue dye in different sites of the breast. METHODS: Prior to surgery 137 breast cancer patients underwent intrasubdermal injection of 30-50 MBq 99mTc-colloidal albumin over the tumour site (ISI group). Ten minutes before surgery, 2 ml patent blue was injected in the subareolar area (SAI group) in 117/137 patients, while 20 patients received intrasubdermal blue-dye in the quadrant opposite the tumour site (OQI group). The different injection routes were considered concordant when the hottest sLN was also blue. RESULTS: In 134/137 patients radiocolloid drained to one or more axillary nodes, while blue nodes were found in 98/117 SAI patients and in 17/20 OQI patients. Multiple hot nodes were found in 63/134 cases and multiple blue nodes in 35/115. In patients in whom both tracers reached the axilla, the hottest node was also blue in 108/115 cases (93/98 SAI and 15/17 OQI patients). In the seven discordant cases, the hottest node was not blue, but in two cases the blue node was also radioactive. CONCLUSIONS: Superficial lymphatic drainage from the breast most frequently merges to a single axillary lymph node, irrespective of the site of tracer injection. In a few cases different injection sites identify different, often closely interconnected sLNs.

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

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

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

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↗
PubMed2002

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗