Anastomotic Leak Rate and Prolonged Postoperative Paralytic Ileus in Patients Undergoing Laparoscopic Surgery for Colo-Rectal Cancer After Placement of No-Coil Endoanal Tube.

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.

No Coil® placement in patients undergoing left hemicolectomy and low anterior resection for colorectal cancer.

BACKGROUND: Colorectal 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). METHODS: Thirty-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. RESULTS: PPOI 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. 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.

Comparison of (18)F-FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Co-expression of CD133(+)/CD44(+) in human colon cancer and liver metastasis.

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.

Mast cell positivity to tryptase correlates with metastatic lymph nodes in gastrointestinal cancer patients treated surgically.

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.

Left hemicolectomy and low anterior resection in colorectal cancer patients: Knight-griffen vs. transanal purse-string suture anastomosis with no-coil placement.

Background: Colorectal cancer (CRC) is considered one of the most frequent neoplasms of the digestive tract with a high mortality rate. Left hemicolectomy (LC) and low anterior resection (LAR) with minimally invasive laparoscopic and robotic approaches or with the open technique are the gold standard curative treatment. Materials and methods: Seventy-seven patients diagnosed with CRC were recruited between September 2017 and September 2021. All patients underwent a preoperative staging with a full-body CT scan. The goal of this study was to compare both types of surgeries, LC-LAR LS with Knight-Griffen colorectal anastomosis and LC-LAR open with Trans-Anal Purse-String Suture Anastomosis (the TAPSSA group), by positioning a No-Coil transanal tube (SapiMed Spa, Alessandria, Italy), in terms of postoperative complications such as prolonged postoperative ileus (PPOI), anastomotic leak (AL), postoperative ileus (POI), and hospital stay. Results: The patients were divided into two groups: the first with 39 patients who underwent LC and LAR in LS with Knight-Griffen anastomosis (Knight-Griffen group) and the second with 38 patients who underwent LC and LAR by the open technique with the TAPSSA group. Only one patient who underwent the open technique suffered AL. POI was 3.76 ± 1.7 days in the TAPSSA group and 3.07 ± 1.3 days in the Knight-Griffen group. There were no statistically significant differences in terms of AL and POI between the two different groups. Conclusion: The important point that preliminarily emerged from this retrospective study was that the two different techniques showed similarities in terms of AL and POI, and therefore, all the advantages reported in the previous studies pertaining to No-Coil also hold good in this study regardless of the surgical technique used. However, randomized controlled trials are needed to confirm these findings.

Duplication cyst of the stomach with respiratory epithelium in adult: an uncommon finding. Report of case and review of literature.

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.

Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients.

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.

Sphincter-saving proctectomy for rectal cancer with NO COIL® transanal tube and without ostoma. Clinical outcomes, cost effectiveness and quality of life in the elderly.

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 (<75 years, N.=302). Rectal anterior resection (RAR) with sphincter-saving restorative proctectomy and with application of silicone transanal tube NO COIL® 60-80 mm long, was the only procedure considered. Main clinical and pathological data were assessed and compared. RESULTS: Statistically significant differences between the two groups were detected regard to comorbidities and the emergency presentation. Overall survival is lower in patients over 75 age, but cancer-related survival is not different between the two groups. CONCLUSIONS: Although advanced age is associated with higher morbidity and mortality, in our experience, itself is not a contraindication for surgical sphincter-saving proctetomy in rectal cancer patients. The absence of a stoma also improved the cost effectiveness and patients' quality of life in both groups: psychological morbidity, sexuality, levels of anxiety and depression, body image.

Isolated splenic metastasis from colon cancer. Report of a case.

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.

Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale.

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/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) 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.

Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic.

Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosine-kinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.

H pylori status and angiogenesis factors in human gastric carcinoma.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Sphincter-saving proctectomy for rectal cancer in the elderly.

AIM: 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. MATERIAL OF STUDY: 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. RESULTS: 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. CONCLUSIONS: 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. KEY WORDS: Outcomes, Rectal Cancer, Elderly, Sphincter-saving, Surgery.

Oestrogen receptor-related receptor alpha (ERRalpha) and oestrogen receptors (ERalpha and ERbeta) exhibit different gene expression in human colorectal tumour progression.

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.

[Prognostic value of thymidylate synthase, topoisomerase-1 and Ki-67 in advanced colorectal cancer patients on irinotecan and fluorouracil treatment].

OBJECTIVE: 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). METHODS: The biomarker expression of TS, Topo-1 and Ki-67 in 78 patients detected immunohistochemically were correlated with the clinical outcome. RESULTS: 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 (P < 0.05) and in OS (P < 0.05). The low expression of Ki-67 was also significantly predictive of longer survival (P < 0.05). 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). CONCLUSION: 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.

Vascular endothelial growth factor assessment in different blood fractions of gastrointestinal cancer patients and healthy controls.

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.

Up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in left-sided human colon cancer.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance.

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.

Mast cells density positive to tryptase correlates with angiogenesis in pancreatic ductal adenocarcinoma patients having undergone surgery.

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 potent in vivo and in vitro proangiogenic 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 stage T2-3N0-1M0 (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's t-test analysis (r ranged from 0.69 to 0.81; P value 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.