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Background Colorectal cancer (CRC) is the second most common gastrointestinal tumor in men and the third in women. Left-hemicolectomy (LC) and low anterior resection (LAR) are considered the gold standard curative treatment. In this retrospective study, we evaluated the presence or absence of post-operative complications, in all patients who underwent Video-laparoscopic (VLS) LAR/LC with No Coil trans-anal tube positioning, and compared the data with the current literature on the topic. Methods Thirty-nine patients diagnosed with CRC of the descending colon, splenic flexure, sigma, and rectum were recruited. LC was performed for sigmoid and descending colon cancers, while LAR was applied for tumors of the upper two-thirds of the rectum. The No Coil trans-anal tube (SapiMed Spa, Alessandria, Italy) was placed in all patients of the study at the end of surgical treatment. Results Eighteen patients received a LAR-VLS (46%) and 21 patients received a LC-VLS (54%). The average length of hospital stay after surgery was 7 days. PPOI occurred in only one in 39 patients (2.6%) who had undergone LAR-VLS. As for complications, in no patient of the study did AL (0%) occur. Conclusion In patients undergoing LAR-VLS and LC-VLS, we performed colorectal anastomosis and in the same surgical operation we introduced the No-Coil device. Although this is a preliminary study and subject to further investigation, we believe that the No Coil tube positioning may reduce the time of presence of first flatus and feces and the risk of AL.

Background. Colorectal cancer (CRC) is the most common type of the gastrointestinal tract. Anastomotic leak (AL), is the most important complication of colorectal surgery. In this retrospective study, we evaluated efficacy and tolerability of transanal tube No Coil® in patients with CRC undergoing low anterior resection (LAR) and left hemicolectomy (LC). Methods. Thirty-eight patients operated by the same team for primary colorectal adenocarcinoma were collected, 24 LC and 14 LAR. Neither defuncioning stoma nor neoadjuvant therapy not was administered to anyone patients. No Coil® was placed immediately after the end of surgical treatment.Results. In our experience, LC was performed in 24 individuals (63%), LAR in 14 individuals (37%). AL was evident in 2,63 % of the sample; no statistical difference was found in AL occurrence between LC and LAR with only one patient in LAR group.Conclusion. With our preliminary data, we suggest that No Coil® placement can be considered as a valuable procedure assisting colorectal surgery, but further studies are required to confirm and enlarge actual evidence.

BackgroundColorectal cancer (CRC) is the most common tumor of the gastrointestinal tract. Anastomotic leak (AL) and prolonged postoperative ileus (PPOI) are two important complications of colorectal surgery. In this observational retrospective study, we evaluated the positive effects of transanal tube No Coil®in patients with CRC undergoing low anterior resection (LAR) and left hemicolectomy (LC).MethodsThirty-eight cases and forty controls resulted eligible for the final sample. No Coil®placement (SapiMed Spa, Alessandria, Italy) was considered an inclusion criteria for the case group. No Coil®was placed immediately after the end of surgical treatment.ResultsPPOI was significantly more frequent in the control group. AL was evident in 1 patient (2.6%) of cases and 3 patients (7.5%) of controls. No statistical difference was found in AL occurrence between groups. POI days and AL resulted associated with hospital stay. POI days were negatively associated with No Coil placement and positively with AL.ConclusionWith our preliminary data, we suggest that No Coil®placement can be considered as a valuable procedure assisting colorectal surgery, but further studies are required to confirm and enlarge actual evidence.

BACKGROUND Colorectal cancer is one of the most common invasive cancers, and it is responsible for considerable physical and psychosocial morbidity specially in older patients. However, only few reports focused on quality of life, cost-effectiveness and clinical outcomes of rectal cancer patients undergone to surgery. This retrospective study compares short-term and long-term outcomes in rectal cancer patients with more and less than 75 years of age. METHODS Four hundred consecutive patients underwent radical surgery for rectal adenocarcinoma and they were collected in a prospective institutional database and divided into two groups: group 1 (≥75 years, N.=98); group 2 (

Rectal cancer shows a high incidence in older patients, however, only few reports focused exclusively on rectal cancer with the exclusion of the surgery of the colon. This retrospective study aims to compare short-term and long-term outcomes for rectal cancer in patients more than 75 years old with that observed in younger patients.Four hundred consecutive patients operated on for primary rectal adenocarcinoma were collected in a prospective institutional database and divided into two groups: group 1 (≥ 75 years, n =98); group 2 (75 years, n= 302). Sphincter-saving restaurative proctectomy was the only procedure considered. Main clinical and pathological data, morbidity, clinical anastomotic leakage, reoperation rate, 30-day mortality, overall survival, and cancer-related survival were assessed and compared.In our experience, advanced age itself is not a contraindication for surgical sphincter-saving proctetomy in rectal cancer patients, although it is associated with higher morbidity and mortality. Overall survival is lower in patients over 75 age, but cancer-related survival is not different between the two groups.In our experience, advanced age itself is not a contraindication for surgical sphincter-saving proctetomy in rectal cancer patients, although it is associated with higher morbidity and mortality. Overall survival is lower in patients over 75 age, but cancer-related survival is not different between the two groups.Outcomes, Rectal Cancer, Elderly, Sphincter-saving, Surgery.Il tumore del retto ha un’alta incidenza nei pazienti anziani ma pochi dati sono presenti in letteratura rispetto al tumore del colon. L’ obiettivo del nostro studio è quello di comparare i risultati in termini di dati clinici e patologici post-operatori, di sopravvivenza e di sopravvivenza cancro-correlata, tra due gruppi di pazienti (gruppo 1: ≥ 75 anni, n =98; gruppo 2:75 anni, n= 302) affetti da tumore del retto sottoposti ad intervento di proctectomia restaurativa con rispetto dell’ integrità anatomo- funzionale dello sfintere anale. I nostri risultati non mostrano nessuna differenza statisticamente significativa tra i due gruppi, in particolar modo per il dato della sopravvivenza cancro-correlata. La sopravvivenza globale risulta essere inferiore nel gruppo dei pazienti anziani rispetto ai pazienti con età minore dei 75 anni.

Literature data indicate that mast cells (MCs) are involved in angiogenesis through the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MC granules, is one of the most active. However, no data are available concerning the role of MCs during keloids' angiogenesis. In this study, we evaluated the correlations of the number of MCs positive to tryptase (MCDPT) and microvascular density (MVD) within a series of 15 keloids and 10 normotrophic scars, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant difference of MVD and MCDPT between keloids and normotrophic scars and a significant correlation between MVD and MCDPT in keloids. Our results suggest that tryptase-positive MCs might play a key role in keloids' angiogenesis. In this context, several tryptase inhibitors might be clinically evaluated as a possible new anti-angiogenetic approach to prevent keloid formation after surgery.

Aims and background Covering stoma is the main method used to protect low-lying anastomosis after cancer proctectomy. Intraluminal rectal pressure could be a potential risk factor for anastomotic leakage. We present our personal experience with an alternative and original device, the transanal tube NO COIL®, evaluating its feasibility and safety based on a preliminary manometric study. Methods From May 1998 to March 1999, an experimental manometric study on 35 subjects was performed to assess the pathophysiological basis of intraluminal rectal pressure with or without the transanal tube. Subsequently, from April 1999 to December 2009, 184 patients (107 males, 77 females, average age 68.2 ± 10 years) with primary adenocarcinoma of the rectum (≤12 cm from anal verge) were selected. Eighty-two underwent total proctectomy and 102 subtotal proctectomy. No stoma were fashioned. At the end of the operation, the silicone transanal tube NO COIL®, 60–80 mm long, 2 mm thick with a calibre of up to 2 cm, was applied and secured to the perineal skin by two stitches, then removed on the seventhpostoperative day if no signs of leakage occurred. Results The intraluminal rectal pressure with transanal tube was strongly reduced from 13.8 + 8.5 mmHg to 4.8 + 3.7 mmHg (P Conclusions The transanal tube NO COIL® does not abolish the risk of anastomotic leakage but could be an alternative option to covering stoma after cancer proctectomy in selected patients. In our experience, this simple and cheap device could reduce the rate of stoma without leakage-related mortality. Further studies within a randomized controlled trial are required to better define our results.

Background Gastrectomy with extended lymphadenectomy is considered the gold standard treatment for advanced gastric cancer, with no age- or comorbidity-related limitations. We evaluated the safety and efficacy of curative gastrectomy with extended nodal dissection, verifying survival in elderly and highly co-morbid patients. Methods In a retrospective multicenter study, we examined 1322 non-metastatic gastric-cancer patients that underwent curative gastrectomy with D2 versus D1 lymphadenectomy from January 2000 to December 2009. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) according to age and the Charlson Comorbidity Score were analyzed in relation to the extent of lymphadenectomy. Results Postoperative morbidity was 30.4%. Complications were more frequent in highly co-morbid elderly patients, and, although general morbidity rates after D2 and D1 lymphadenectomy were similar (29.9% and 33.2%, respectively), they increased following D2 in highly co-morbid elderly patients (39.6%). D2-lymphadenectomy significantly improved 5-year OS and DSS (48.0% vs. 37.6% in D1, pÂ

Purpose We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. Patients and Methods A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m2 on day 1 with LV5FU2 regimen). Results One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. Conclusion There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5-Fluorouracil (5-FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT-11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy. TS and Topo-I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, p

The aim of this study was to prospectively investigate the predictive value of (18)F-FDG PET/CT semiquantitative parameters for locally advanced low rectal cancer (LARC) treated by neoadjuvant chemoradiation therapy (nCRT).68 patients with LARC had (18)F-FDG PET/CT scans twice (baseline and 5-6 weeks post-nCRT). All patients underwent surgery with preservation of the sphincter 8 weeks later. (18)F-FDG PET/CT analysis was performed by visual response assessment (VRA) and semiquantitative parameters: SUVmax(baseline), SUVmean(baseline), MTV(baseline), TLG(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), TLG(post-nCRT); ΔSUVmax and mean and Response indexes (RImax% and RImean%). Assessment of nCRT tumor response was performed according to the Mandard's Tumor Regression Grade (TRG) and (y)pTNM staging on the surgical specimens. Concordances of VRA with TRG, and with (y)pTNM criteria were evaluated by Cohen's K. Results were compared by t student test for unpaired groups. ROC curve analysis was performed.VRA analysis of post-nCRT (18)F-FDG PET/CT scan for the (y)pTNM outcome showed sensitivity, specificity, accuracy, PPV, and NPV of 87.5%, 66.7%, 83.8%, 92.5%, and 53.3%, respectively. Concordances of VRA with TRG and with (y)pTNM were moderate. For the outcome variable TRG, the statistical difference between responders and non-responders was significant for SUVmax(post-nCRT) and RImean%; for the outcome variable (y)pTNM, there was a significant difference for MTV(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. ROC analysis showed better AUCs: for the outcome variable TRG for SUVmax(post-nCRT), SUVmean(post-nCRT), and RImean%; for the outcome variable (y)pTNM for MTVbaseline, SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. No significant differences among parameters were found.Qualitative and semiquantitative evaluations for (18)F-FDG PET/CT are the optimal approach; a valid parameter for response prediction has still to be established.

The topic chosen by the Board of the Italian Society of Surgery for the 2013 annual Consensus Conference was gastric cancer. With this purpose, under the direction of 2 chairmen, 36 experts nominated by the Regional Societies of Surgery and by the Italian Research Group for Gastric Cancer (GIRCG) participated in an experts consensus exercise, preceded by a questionnaire and mainly held by telematic vote, in accordance with the rules of the Delphi method. The results of this Consensus Conference, presented to the 115th National Congress of the Italian Society of Surgery, and approved in plenary session, are reported in the present paper.

Background: Angiogenesis has been found to be a reliable prognostic indicator for several types of malignancies. Tryptase is a serine protease stored in mast cell (MC) granules, which plays a role in tumor angiogenesis. MCs can release tryptase following c-Kit receptor activation. Method: In this study, immunohistochemistry, image analysis methods and clinical aspects were employed in a series of 41 gastrointestinal cancer patients with stage T3-4N2a-bM₀ (by the American Joint Committee on Cancer, AJCC, for colorectal cancer, 7th edition) and T3N2-3M₀ (by AJCC for gastric cancer, 7th edition) to evaluate the possible correlation between MCs positive to tryptase (MCPT) in tumor tissue and the number of metastatic lymph nodes harvested. Results: Data demonstrated a positive correlation between MCPT in tumor tissue and the number of metastatic lymph nodes; the validity of these data needs confirmation in larger patient cohorts. Conclusion: This is the first report considering MCPT in tumor tissue as a potential tool for a valid indication of the type of surgical treatment and its radicality, and it might be considered for the prognosis of patients before radical surgical treatment. Our pilot data need confirmation in a larger patient cohort.

Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, non-tumor tissue and liver metastasis were obtained directly from the operating room, examined, and immediately processed. CSCs were selected under serum-free conditions and characterized by CD44 and CD133 expression levels. CD133+/CD44+ cell populations were then investigated in paraffin-embedded tissues and circulating tumor cells isolated from peripheral blood of the same group of colon cancer patients. Our data demonstrate that metastatic properties of cell populations from blood and liver metastasis, differently from primitive tumors, seem to be strictly related to the phenotype CD133 positive and CD44 positive. J. Cell. Physiol. 228: 408–415, 2013. © 2012 Wiley Periodicals, Inc.

Gastrointestinal duplication is a congenital rare disease entity. Duplication cyst of the stomach with pseudo stratified columnar ciliated epithelium is extremely rare. The very appearance of a gastric duplication cyst in an adult can present a diagnostic dilemma. In majority of reported cases, the diagnosis is established during surgical exploration. We report on a 34 year-old female patient suffering from repeated episodes of epigastric pain and gastroesophageal reflux. Abdominal computed tomography and endoscopic ultrasound demonstrated a intramural lesion attached to the gastric fundus, suggestive of gastrointestinal stromal tumor (GIST). At exploratory laparotomy a non-communicating cyst, was found along the greater curvature of the stomach in the esophagogastric transition. The lesion was excised along with an adjacent sleeve of the stomach and esophagus wall because shared muscular layer with the stomach and esophagus. The final pathologic examination revealed that the inner wall of the cyst was lined by a pseudostratified columnar ciliated epithelium (respiratory type) and, in part, columnar and gastric foveolar epithelium. Even though a panel of imaging modalities is available, it is still difficult to obtain a preoperative diagnosis. Duplication cyst can be mistaken for a soft tissue tumor of the gastrointestinal tract. There is no therapeutic algorithm. Surgical treatment is recommended for symptomatic cases.

The non-isotopic assay (NIRCA), based on the observation that RNAse is able to specifically cleave a single mismatch in RNA/RNA duplexes, has been recently proposed to detect p53 mutations. To verify the use of this method as a valid screening for P53 mutations in a routinely collected cancer series, we used this assay on 3 cases with normal and 5 cases with abnormal P53 expression detected by Western blots. In all cases, P53 exons 5–6, 7 and 8–9 regions were analyzed. There were mutations only in the five overexpressed cases: two cases showed mutations in exon 5, one between intron 6 and exon 6 and two in the region spanning exons 8 and 9. Our experience showed NIRCA to be fast, reliable and providing the ability to study long target regions in a single step, thus making this assay useful for genetic screenings.

Literature data indicate that mast cells (MCs) are involved in tumor angiogenesis due to the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MCs granules, is one of the most active. However, no data are available concerning the role of MCs in angiogenesis in primary human breast cancer. In this study, we have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the area occupied by MCs positive to tryptase (MCAPT) and microvascular density (MVD) and endothelial area (EA) in a series of 88 primary T1-3, N0-2 M0 female breast cancer, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant (r = from 0.78 to 0.89; p-value from 0.001 to 0.002 by Pearson's analysis respectively) correlation between MCDPT, MCAPT, MVD, EA to each other. No correlation concerning MCDPT, MCAPT, MVD, EA and the main clinicopathological features was found. Our results suggest that tryptase-positive MCs play a role in breast cancer angiogenesis. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new anti-angiogenetic approach.

Isolated splenic metastasis is an uncommon event, except in the case of secondary involvement by lymphoma. The most common sites of metastases of colorectal cancer are the regional lymph nodes, liver and peritoneum; lung and bone are rarely involved, the spleen exceptionally. In this paper we report a case of metachronous isolated splenic metastasis of transverse colon cancer in an 80-year-old woman who was successfully treated by splenectomy. The peculiar clinical-pathological aspects of this kind of metastasis are discussed on the basis of our clinical observation and a review is presented of similar cases reported in the literature. Only 14 reported cases of isolated splenic metastasis from colorectal cancer were found in Medline.

A 50-year-old unmarried rural man was referred for a giant painless scrotal lump which had developed over a period of about six years. At the admission physical examination disclosed a large swelling scrotum and palpable left supraclavicular lymph nodes. Blood counts, renal and hepatic function tests, lactate dehydrogenase, beta-HCG, and alpha-fetoprotein were normal. Computed tomographic scan of thorax and abdomen revealed supraclavicular, mediastinal, and retroperitoneal adenopathies. The patient underwent right-sided radical orchiectomy. The final pathological diagnosis was paratesticular spindle cell rhabdomyosarcoma. Unfortunately, few days after surgery, patient presented a clinical and laboratory picture of disseminated intravascular coagulation followed by exitus.

To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels.Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively.A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026).H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

To investigate the prognostic value of thymidylate synthase (TS), topoisomerase-1 (Topo-1), and proliferating index Ki-67 in advanced colorectal cancer patients on irinotecan (CPT-11) in combination with fluorouracil treatment (5-Fu).The biomarker expression of TS, Topo-1 and Ki-67 in 78 patients detected immunohistochemically were correlated with the clinical outcome.The expressions of those biomarkers were not correlated with clinical therapeutic response, but with time to progression (TTP) and/or overall survival (OS). Patients with low expression of TS had significantly longer TTP (P0.05) and in OS (P0.05). The low expression of Ki-67 was also significantly predictive of longer survival (P0.05). As compared with any biomarker, the combination of any two biomarkers still possessed no predictive value to therapeutic response, but an enhanced predictive value to prognosis. The median time to progression in patients with low expression of TS, or Ki-67, or both were 9, 8 and 17 months, respectively; in patients with low expression of TS, or Topo-1, or both were 9, 9 and 13 months; in patients with low expression of Topo-1, or Ki-67, or both were 8, 9 and 11 months. TTP was significantly longer in patients with low expression of two biomarkers as compared with those with high expression (P = 0.031).TS, Topo-1, and Ki-67 are not predictive for chemotherapy response to CPT-11 combined with 5-Fu, but valuable in predicting prognosis. The combination of any two biomarkers can provide more powerful prognostic information for advanced colorectal cancer patients.

We evaluated the HMGCoA reductase activity and LDL receptor levels in human colon cancer as well as the effects of simvastatin on in vitro cell growth and apoptosis of DLD-1 and Caco2 cell lines.HMGCoA reductase activity and LDL receptor were measured by radiochemical assay and ELISA method, respectively. Cell growth and apoptosis were evaluated by MTT-test and DNA fragmentation analysis, respectively.Higher HMGCoA reductase activity and LDL receptor levels were detected in cancer than in normal mucosa. An up-regulation of HMGCoA reductase activity was detected in left-sided tumors. Simvastatin treatment produced marked anti-proliferative and pro-aptotic effects in DLD-1. Cell growth inhibition, but no apoptosis, was also evident in Caco2 cells.The cholesterol pathway is involved in colon malignant transformation. Therapeutic strategies using HMGCoA reductase inhibitors as anti-cancer compounds should also take into consideration the biological and clinical differences detected inside colon tracts.

We have investigated the presence of oestrogen receptor-related (ERR) mRNA in human colorectal tumour tissues and adjacent normal mucosa by reverse transcriptase and nested-polymerase chain reaction. ERRalpha was found in 100% of the patients and ERRgamma in approximately 30% while ERRbeta was not detected at all. The multiplex PCR analysis showed elevated levels of ERRalpha mRNA in tumour tissue compartment as compared to normal mucosa, whereas ERRgamma mRNA was found in lower levels but in both tissue compartments. In contrast, oestrogen receptor (ERalpha and ERbeta) mRNA levels were shown to be decreased in tumour tissues. A positive correlation was observed between ERalpha and ERbeta and between ERalpha and ERRalpha, respectively, in normal mucosa but not in tumour tissue. ERRalpha expression in tumour tissues significantly increased from TNM stages II to IV, whereas both ERs progressively declined. These findings suggest that ERRalpha, as well as the two ERs, might play a critical role in the progression of the colorectal cancer.

Vascular endothelial growth factor (VEGF) is known to play a central role in tumour angiogenesis. Up to now inconclusive data have been published on the clinical-biological significance of circulating VEGF and on the most suitable blood fraction for measuring it. The aims of this pilot study were to assess VEGF in blood compartments of 16 healthy control volunteers and 56 gastrointestinal cancer patients, prospectively collected, to identify the most suitable blood fraction for the determination of VEGF and to evaluate its possible clinical-biological significance. Samples of serum (S) and plasma (P) in both sodium citrate (SC) and sodium citrate-theophylline-adenosine-dipyridamole (CTAD) were collected from venous blood. After the centrifugation and separation methods VEGF levels were detected by ELISA in: S, plasma-platelets poor (P-PP), plasma-activated platelets rich (P-APR) and blood-lysed whole (B-LW). The best differentiation between healthy control volunteers and cancer patients in VEGF level was seen for P-APRCTAD (mean value: 278 pg/ml vs 77 pg/ml; p=0.0036 by t-test). No significant correlation among the blood fractions of VEGF analysed and clinical-pathological features was found. Our data suggest that P-APRCTAD blood fraction, obtained according to well standardised conditions, could represent the most suitable compartment for the assessment of VEGF. We suggest that VEGF levels in P-APRCTAD could play a role as an angiogenic marker of malignant gastrointestinal transformation. Further studies on a larger series of patients and healthy controls with the same experimental methodological conditions are required to confirm our preliminary conclusions.

e21134 Background: Tryptase is a serin protease stored in mast cell granules that plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor activation. On the other hand colo-rectal cancer (CRC) is a well-established angiogenesis dependent tumour and anti-angiogenic based therapy is a standard treatment in metastatic CRC. This preliminary study aims to assess tryptase serum levels in 51 CRC patients before and after radical surgery. Methods: In this study patients with stage B and C CRC (according to Astler e Coller staging system) were selected. Samples of blood were taken from CRC patients between 7 and 9 a.m.1 day before and 1 day after curative surgery. Venous blood was dispensed into a tube for serum (Becton Dickinson Hemogard Vacutainer Systems, Plymouth, UK). Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia,Uppsala, Sweden). Primary tumour tissue were also evaluated in terms of MCs positive to tryptase by immunohistochemistry utilizing an anti-tryptase primary antibody (clone AA1; Dako, Glostrup, Denmark). Results: Mean ± s.d. tryptase level pre-tumour surgical resection was 6.37 ± 4.57 μg/L, and mean ± s.d. tryptase level post tumour surgical resection was 5.15 ± 3.82 μg/L. A statistically significant difference between pre-tumour surgical resection and post-tumour surgical resection tryptase level concentrations was found: p=0.000 by t-test. A statistically significant correlation between MCs positive to trypase and serum tryptase levels pre-surgical resection was also found (r=086; p=0.000) by Pearson’s analysis. Conclusions: This pilot report analyzes the possible significance of serum tryptase levels changes in CRC patients who underwent curative surgery. Our results demonstrated higher serum tryptase levels CRC patients suggesting the release of tryptase from MCs of primary CRC tissue. As expected, after radical surgical resection, serum tryptase levels had decreased. We suggest that tryptase may play a role as a new predictive biomarker in CRC patients. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated as adjuvant treatment in clinical trials.

e13526 Background: ECT is an effective local treatment for palliation on inoperable superficial neoplastic lesions from any type of tumour. It combines chemotherapy and electric pulses that permeabilize the cell membrane in a transient and reversible manner, allowing low-perrneant drugs to enter the cell, thus magnifying their cytotoxicity. Recent1y, a new device (Clinoporetor, IGEA-Srl, Italy) has been developed to supply electric pulses with appropriate parameters permitting the clinical use of ECT. Methods: We treated 26 pts, M/F 12/14; median age 61 yrs, range 38–87: 7 breast cancer with nodular or infiltrating lesions in thoracic or abdominal wall; 12 melanoma (2 wide infiltration of thoracic wall, 10 in transit metastases or loco-regional recurrences); 2 head-neck cancer with a wide neck-scalp infiltration; 3 lymphomas with cutaneous lesions, 1 soft tissue sarcoma with a subcutaneous recurrence, 1 gastric cancer with 2 cutaneous localizations. The areas treated ranged from 1 to 30 cm on diameter. 12 pts requested a prior surgery debulking and 3 pts received ECT in pre-irradiated area. Intravenous bleomycin (15 mg/m2) were used in all patient; electric pulses were than applied to the tumor areas by needle electrodes in a time window of 20 minutes. In total 32 procedures were performed, 6 as out-patient in local anaesthesia and 26 in general anaesthesia; 6 pts requested a second application. Results: Treatment was safe and well tolerated, particularly when general anaesthesia was used. At the second/third week, all pts showed a regression of almost all lesions with a necrotic, fibro-sclerotic evolution. After 1–2 months from ECT, we obtained a 70% CR and a 10%PR of the lesions. Some pts showed a response after the second procedure. About 50% of lesions remained in remission for a long period (median 8 months, range 1–23+); 11 of 12 pts previously undergone surgical debulking never relapsed in the treated area. Concomitant systemic treatment, no rapid spreading of the disease and surgical debulking were related to a better local control and survival. Conclusions: ECT is a promising and safe treatment for superficial lesions from different malignancies. General anaesthesia and surgical debulking permit to treat very large and deeper lesion with a very good local control. No significant financial relationships to disclose.

20025 Background: ECT is an effective local treatment for palliation on inoperable superficial neoplastic localizations which combines chemotherapy and electric pulses that permeabilize the cell me...

This study prospectively assessed18F-FDG PET/CT in predicting the response of locally advanced low rectal cancer (LRC) to neoadjuvant chemoradiation (nCRT).Methods. 56 patients treated with chemoradiation underwent two18F-FDG PET/CT scans (baseline and 5-6 weeks post-nCRT).18F-FDG uptake (SUVmax and SUVmean) and differences between baseline (SUV1) and post-nCRT (SUV2) scans (ΔSUV and RI%) were evaluated. Results were related to the Mandard’s TRG and (y)pTNM.Results.18F-FDG PET/CT sensitivity, specificity, accuracy, PPV and NPV resulted in 88.6%, 66.7%, 83.92%, 90.7%, and 61.5%. SUV2 resulted in better than SUV1 to predict nCRT response by TRG, with no significant statistical difference between the SUVmax2 and SUVmean2 AUC (0.737 versus 0.736;P=0.928). The same applies to the (y)pTNM (0.798 versus 0.782;P=0.192). In relation to the TRG, RI values had a higher AUC than ΔSUV, with no significant difference between RImax and RImean (0.672 versus 0.695;P=0.292). The same applied to the (y)pTNM (0.742 versus 0.741;P=0.940). In both cases ΔSUV does not appear to be a good predictive tool. Logistic regression confirmed the better predictive role of SUVmax2 for the (y)pTNM (odds ratio = 1.58) and SUVmean2 for the TRG (odds ratio = 1.87).Conclusions.18F-FDG PET/CT can evaluate response to nCRT in LRC, even if more studies are required to define the most significant parameter for predicting pathologic tumor changes.

Objective: Farnesyl diphosphate synthase (FPPs) produces FPP which is considered a branch-point intermediate in the synthesis of sterols and isoprenylated cellular metabolites. In this study we investigated whether detectable FPPs activity was present in human colorectal cancer (CRC), also evaluating in vitro the role of this enzyme in the growth and apoptosis of CRC cells by using Pamidronate (PAM), a FPPs activity inhibitor. Methods: The activity level of FPPs was determined in CRC and the normal surrounding mucosa of 50 patients by radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50 patients by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis. Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were measured by MTT test and DNA fragmentation, respectively. Results: FPPs activity was detectable in human CRC. FPPs activity and its mRNA were significantly more abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a significant reduction of cell growth and also gave rise to a marked proapoptotic effect. Conclusions: This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation.