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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 (

Background. Angiogenesis is a complex process involved in both growth and progression of several human and animal tumours. Tryptase is a serin protease stored in mast cells granules, which plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation.Method. In a series of 25 gastric cancer patients with stage T3N2-3M0(by AJCC for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods were employed to evaluate in the tumour tissue the correlation between the number of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC), and microvascular density (MVD).Results. Data demonstrated a positive correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and MVD was significantly (r=0.64,P=0.001;r=0.66,P=0.041, resp.).Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role in gastric cancer angiogenesis, so we think that several c-KitR or tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach.

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.

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. Literature data suggest that cells such as mast cells (MCs), are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potentin vivoandin vitroproangiogenic factor. Nevertheless few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed MCs and angiogenesis in primary tumour tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC).Method. A series of 31 PDAC patients with stageT2-3N0-1M0(by AJCC for Pancreas Cancer Staging 7th Edition) was selected and then underwent surgery. Tumour tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCs positive to tryptase (MCDPT), area occupied by MCs positive to tryptase (MCAPT), microvascular density (MVD), and endothelial area (EA). The above parameters were related to each other and to the main clinicopathological features.Results. A significant correlation between MCDPT, MCAPT, MVD, and EA group was found by Pearson’st-test analysis (rranged from 0.69 to 0.81;Pvalue ranged from 0.001 to 0.003). No other significant correlation was found.Conclusion. Our pilot data suggest that MCs positive to tryptase may play a role in PDAC angiogenesis and they could be further evaluated as a novel tumour biomarker and as a target of antiangiogenic therapy.

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.

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.

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.

Background Tryptase is a serin protease stored and released from mast cells (MCs) that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC) patients before (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT) and microvascular density (MVD) in primary tumour tissue. Methods A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system) were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated by image analysis methods. Results The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT and MVD (r = 0.73; p = 0.001) was found. Conclusion Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.

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.