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Francesco Tonelli

Publications and source records attributed to Francesco Tonelli.

At least 19 recordsLinked to original sources
PubMed2007

Balance between endoscopic and genetic information in the choice of ileorectal anastomosis for familial adenomatous polyposis.

BACKGROUND AND OBJECTIVES: The number of rectal polyps and the site of mutations in the APC (Adenomatous polyposis coli) gene have been used to guide the surgical management in patients with familial adenomatous polyposis (FAP). The aim of this study is to assess the utility of the APC mutation screening compared to the degree of the rectal polyposis in surgical decision making. METHODS: The post-surgical courses of 25 patients submitted to subtotal colectomy with ileorectal anastomosis (IRA) were reviewed. Preservation of the rectum was prospectively decided on the basis of well-defined endoscopic criteria. The number of rectal polyps was assessed preoperatively and every 6-12 months. APC gene was screened for mutations by heteroduplex analysis, single strand conformation polymorphism, in vitro synthesized protein (IVSP), and DNA sequencing. Patients negative for APC mutations were tested for MYH mutations. RESULTS: On the basis of preoperative polyp rectal count we categorized patients as follows: Group I, 5 or fewer adenomas; Group II, 6-9 adenomas; Group III, 10 or more adenomas. After a follow-up ranging from 12 to 225 months we have observed a significant difference of recurrent rectal adenomas between Groups I-II versus III. No difference was detected among patients of Group I and II. The mean number of adenomas/year/patient was 0.67, 1.62, and 9.29 for Group I, II, and III, respectively. Carpeting polyposis of the rectal stump developed in three patients with APC mutation at codon 1309 and two of them needed later proctectomy. Diffuse rectal polyposis was observed in one patient with mutation at exon 9 who had 10 small polyps at time of surgery. Mutation at the 5'-end of APC (codons 144-232), mutation of MYH and unknown APC or MYH mutation were correlated with a low number of polyps both at presentation and follow-up. No IRA patients developed rectal cancer. CONCLUSIONS: In our experience fewer than 10 rectal polyps at presentation can predict a favorable outcome after IRA. Identification of specific germ-line APC or MYH mutation can address the choice of surgical treatment.

Adenomatous Polyposis Coli↗
PubMed2006

Well-differentiated endocrine tumor of the distal common bile duct: a case study and literature review.

Primary carcinoid tumors of the extrahepatic biliary tree are exceedingly rare, accounting for 0.2-2% of all digestive carcinoids. The authors in this study describe a case of biliary duct primary well-differentiated endocrine tumor in a 30-year-old man with symptoms of biliary obstruction and watery diarrhoea. Abdominal ultrasound showed a 2-cm solid lesion in the head of the pancreas, compressing the distal common bile duct. A computed tomography scan confirmed these findings, revealing the hypervascular pattern of the tumor. Gastrointestinal hormonal screening demonstrated an increase in plasma serotonin. The patient underwent standard pylorus-preserving pancreatoduodenectomy. Pathological examination showed a neuroendocrine tumor of the distal common bile duct measuring 1.8 cm in greatest dimension. The tumor cells were immunopositive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, serotonin, and cytokeratin. Stains for gastrin and somatostatin were negative. Seven years later, the patient is well, with no evidence of disease. Given the site of these tumors and the difficulty in differentiating them from periampullary lesions, decisions as to the appropriate surgical approach may be problematic. After an exhaustive review of the literature, the authors conclude that pancreatoduodenectomy is the treatment of choice.

Adult↗
PubMed2006

Treatment of perianal fistulas in Crohn's disease by local injection of antibody to TNF-alpha accounts for a favourable clinical response in selected cases: a pilot study.

OBJECTIVE: Intravenously administered infliximab, a monoclonal antibody directed against tumor necrosis factor-alpha, has been proven to be efficacious in the treatment of fistulas in patients with Crohn's disease. It has recently been suggested that local injections of infliximab might be beneficial as well. The aim of this study was to assess whether infliximab could play an effective role in the local treatment of perianal fistulas in Crohn's disease. MATERIAL AND METHODS: Local infliximab injections were administered to 11 patients suffering from Crohn's disease complicated by perianal disease. Eligible subjects included Crohn's disease patients with single or multiple draining fistulas, regardless of status of luminal disease at baseline. Patients, however, were excluded from the study if they had perianal or rectal complications, such as abscesses or proctitis or if they had previously been treated with infliximab. Twenty-milligram doses of infliximab were injected along the fistula tract and around both orifices at baseline and then every 4 weeks for up to 16 weeks or until complete cessation of drainage. No further doses were administered to patients who did not respond after three injections. Efficacy was measured in terms of response (a reduction in fistula drainage of 50% or more) and remission (complete cessation of fistula drainage for at least 4 weeks). Time to loss of response and health-related quality of life were also evaluated. RESULTS: Overall, 8/11 patients (72.7%) responded to the therapy and 4/11 (36.4%) reached remission, whereas 3/11 patients (27.2%) showed no response. Response or remission was very much dependent on the location of the fistulas, and time to loss of response was generally longer for patients who reached remission compared to patients in response. Changes in health-related quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ), also reflected response or remission, with more marked improvements associated with remission. After a mean 10.5 months' follow-up (range 7-18 months), 6/11 patients (54.5%) are in response and 4/11 patients (36.4%) are in remission. No adverse events have been observed in this cohort of patients. CONCLUSIONS: Local injections of infliximab along the fistula tract seem to be an effective and safe treatment of perianal fistulas in Crohn's disease. However, further controlled clinical investigations are warranted.

Adult↗
PubMed2006

A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project.

SUMMARY BACKGROUND DATA: The epidemiology of venous thromboembolism (VTE) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis (DVT). However, the clinical relevance of asymptomatic venography-detected DVT is unclear, and the population of these clinical trials is not necessarily representative of the overall cancer surgery population. OBJECTIVE: The aim of this study was to evaluate the incidence of clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE. METHODS: @RISTOS was a prospective observational study in patients undergoing general, urologic, or gynecologic surgery. Patients were assessed for clinically overt VTE occurring up to 30 +/- 5 days after surgery or more if the hospital stay was longer than 35 days. All outcome events were evaluated by an independent Adjudication Committee. RESULTS: A total of 2373 patients were included in the study: 1238 (52%) undergoing general, 685 (29%) urologic, and 450 (19%) gynecologic surgery. In-hospital prophylaxis was given in 81.6% and postdischarge prophylaxis in 30.7% of the patients. Fifty patients (2.1%) were adjudicated as affected by clinically overt VTE (DVT, 0.42%; nonfatal pulmonary embolism, 0.88%; death 0.80%). The incidence of VTE was 2.83% in general surgery, 2.0% in gynecologic surgery, and 0.87% in urologic surgery. Forty percent of the events occurred later than 21 days from surgery. The overall death rate was 1.72%; in 46.3% of the cases, death was caused by VTE. In a multivariable analysis, 5 risk factors were identified: age above 60 years (2.63, 95% confidence interval, 1.21-5.71), previous VTE (5.98, 2.13-16.80), advanced cancer (2.68, 1.37-5.24), anesthesia lasting more than 2 hours (4.50, 1.06-19.04), and bed rest longer than 3 days (4.37, 2.45-7.78). CONCLUSIONS: VTE remains a common complication of cancer surgery, with a remarkable proportion of events occurring late after surgery. In patients undergoing cancer surgery, VTE is the most common cause of death at 30 days after surgery.

Aged↗
PubMed2006

Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias.

OBJECTIVE: The aim of this study was to evaluate the results of pancreatic resection in pancreatic endocrine neoplasias (PENs) in patients affected by multiple endocrine neoplasia type 1 (MEN1) syndrome. BACKGROUND: Since these tumors often show an indolent course, the role of diagnostic procedures and type of surgical approach are controversial. Experience with new diagnostic approaches and more aggressive surgery is still limited. METHODS: Sixteen MEN1 patients were referred to our Surgical Unit (1992-2003) and were operated on for the indications of hypergastrinism, hypoglycemia, and/or pancreatic endocrine neoplasias larger than 1 cm. Zollinger-Ellison syndrome (ZES) was present in 13 patients, 2 of whom experienced a recurrence after previous surgery. Preoperative tumor localization was carried out using ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), somatostatin receptor scintigraphy (SSRS), or selective arterial secretin injection (SASI). Rapid intraoperative gastrin measurement (IGM) was carried out in 8 patients, and 1 patient also underwent an intraoperative secretin provocative test. RESULTS: Either pancreatoduodenectomy (PD) or total pancreatectomy (TP) or distal pancreatectomy was performed. There was no postoperative mortality; 37% complications included pancreatic (27%) and biliary (6%) fistulas, abdominal collection (6%), and acute pancreatitis (6%). EUS and SSRS were the most sensitive preoperative imaging techniques. At follow-up, 10 of 13 hypergastrinemic patients (77%) are currently eugastrinemic with negative secretin provocative test, while 3 are showing a recurrence of the disease. All patients affected by insulinoma were cured. CONCLUSIONS: MEN1 tumors should be considered surgically curable diseases. IGM may be of value in the assessment of surgical cure. Our experience suggests that PD is superior to less radical surgical approaches in providing cure with limited morbidity in MEN1 gastrinomas and pancreatic neoplasias.

Adult↗
PubMed2006

Redox state and O2*- production in neutrophils of Crohn's disease patients.

The aim of this in vitro study was to evaluate the intracellular redox state and respiratory burst (RB) in neutrophils of patients with Crohn's disease (CD). The intracellular redox state and RB in neutrophils was assessed by the superoxide anion (O2*-) production induced in these cells after stimulation by various factors related to the molecular mechanisms that, if altered, may be responsible for an abnormal immune response. This can, in part, cause the onset of inflammation and tissue damage seen in CD. This study demonstrated a decreased glutathione/glutathione disulfide (GSH/GSSG) ratio index of an increased oxidative state in CD patient neutrophils. Moreover, our findings showed a decrease in tumor necrosis factor (TNF-alpha)- or phorbol 12-myristate 13-acetate (PMA)-induced O2*- production in CD patient neutrophils adherent to fibronectin as compared with controls. A decreased adhesion was also demonstrated. For this reason, the involvement of altered mechanisms of protein kinase C (PKC) and beta-integrin activation in CD patient neutrophils is suggested. These data also showed that the harmful effects of TNF-alpha cannot be caused by excessive reactive oxygen species (ROS) production induced by neutrophils. Decreased cell viability after a prolonged time of adhesion (20 hrs) was also measured in CD patient neutrophils. The findings of this study demonstrate, for the first time, that granulocyte-macrophage colony-stimulating factor (GM-CSF), a compound recently used in CD therapy, is able to activate the RB for a prolonged time both in control and CD patient neutrophils. Increased viability of CD patient neutrophils caused by GM-CSF stimulation was also observed. In conclusion, our results indicate that decreased O2*- production and adhesion, caused, in part, by an anomalous response to TNF-alpha, together with low GSH level and low cell viability, may be responsible for the defective neutrophil function found in CD patients. This can contribute to the chronic inflammation and relapses that characterize this pathology. A possible role of GM-CSF in inducing O2*- production and in restoring the defensive role of neutrophils in CD patients is suggested.

Adult↗
PubMed2005

Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.

The analysis of APC and MYH mutations in adenomatous polyposis coli patients should provide clues about the genetic heterogeneity of the syndrome in human populations. The entire coding region and intron-exon borders of the APC and MYH genes were analyzed in 60 unrelated Italian adenomatous polyposis coli patients. APC analysis revealed 26 point mutations leading to premature termination, one missense variant and one deletion spanning the entire coding region in 32 unrelated patients. Novel truncating point mutations included c.1176_1177insT (p.His393_PhefsX396), c.1354_1355del (p.Val452_SerfsX458), c.2684C>A (p.Ser895X), c.2711_2712del (p.Arg904_LysfsX910), c.2758_2759del (p.Asp920_CysfsX922), c.4192_4193del (p.Ser1398_SerfsX1407), c.4717G>T (p.Glu1573X) and a novel cryptic APC exon 6 splice site. MYH analysis revealed nine different germline variants in nine patients, of whom five were homozygotes or compound heterozygotes. The mutations included 4 novel MYH missense variants (c.692G>A, p.Arg231His; c.778C>T, p.Arg260Trp; c.1121T>C, p.Leu374Pro; and c.1234C>T, p.Arg412Cys) affecting conserved amino acid residues in the ENDO3c or NUDIX domains of the protein and one novel synonymous change (c.672C>T, p.Asn224Asn). Genotype-phenotype correlations were found in carriers of APC mutations but not in carriers of biallelic MYH mutations, except for a negative correlation with low number of polyps. A distinctive characteristic of patients negative for APC and MYH mutations was a significantly (p<0.0001) older age at diagnosis compared to patients with APC mutations. Moreover, the proportion of cases with an attenuated polyposis phenotype was higher (p = 0.0008) among patients negative for APC and MYH mutations than among carriers of APC or biallelic MYH mutations.

Adenomatous Polyposis Coli↗
PubMed2005

Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers.

Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The TS gene promoter enhancer region contains two different polymorphisms which can influence TS mRNA transcriptional and translational efficiency: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism (SNP), G > C, within the second repeat of the 3R alleles. We studied the relationship between tumoural TS mRNA expression levels and TS gene polymorphisms in the colonic mucosa of 48 colorectal cancer patients. The 3R/3R genotype was characterised by higher TS mRNA levels in the tumour than the 2R/2R-2R/3R genotypes (P = 0.071). Regarding the relationship with the SNP polymorphism, a statistically significant difference in TS gene expression between the 3RG/3RG genotype and 2R/2R-2R/3RC-2R/3RG genotype subset was observed (P = 0.017). No statistically significant correlation was observed between experimental data and baseline clinical-pathological characteristics as well as clinical outcome in the relatively small patient series investigated. This is the first study reporting an association between the TS intra-repeat SNP and gene expression levels in colorectal cancer patients. These results suggest that in 3R/3R patients, the G > C polymorphism may be an important factor in determining TS mRNA expression levels, and warrant further investigation of the role of TS promoter polymorphisms as predictors of sensitivity to 5-FU-based chemotherapy in larger case series.

Adult↗
PubMed2005

ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components.

Several strands of evidence indicate that oestrogens exert a protective role against the development of colon cancer through indirect and direct effects on colonic epithelium. Oestrogen receptor beta (ERbeta), the predominant ER subtype in human colon, is significantly decreased in colonic tumours compared with normal mucosa suggesting a potential role in the regulation of colon tumour growth. To investigate this hypothesis we engineered human colon cancer ERalpha-negative HCT8 cells in order to obtain ERbeta protein over-expression. Stably transfected cells were cloned and ERbeta expression and functionality were monitored by RT-PCR, Western blotting and transactivation in an assay using oestrogen-responsive reporter constructs. Over-expression of ERbeta inhibited cell proliferation and increased cell adhesion in a ligand-independent manner. Its constitutive activation is possibly due to cross-talk with intracellular signalling pathways, as epidermal growth factor and IGF-I were able to induce ERbeta transactivation. A possible mechanism by which ERbeta over-expression inhibits proliferation in HCT8 cells is by modulation of some key regulators of the cell cycle; there is a decrease in cyclin E and an increase in the cdk inhibitor p21CIP1. In fact, flow cytometry analysis provided evidence for blocking of the G1-S phase progression induced by ERbeta over-expression. The magnitude of this effect was affected by the level of ERbeta expression. These results provide the first direct evidence that ERbeta plays an important role in colon cancer as a regulator of cell proliferation through the control of key cell cycle modulators and arrest in G1-S phase transition. These findings are compatible with the hypothesis that the loss of ERbeta expression could be one of the events involved in the development or progression of colon cancer.

Apoptosis↗
PubMed2005

Comparison of Wirsung-jejunal duct-to-mucosa and dunking technique for pancreatojejunostomy after pancreatoduodenectomy.

BACKGROUND: Pancreato-enteric reconstruction after pancreatoduodenectomy (PD) is still a source of debate because of the high incidence of complications. Among the various types of pancreato-jejunostomies we don't know yet which is the best in terms of anastomotic failure and related complications rates. Wirsung-jejunal duct-to-mucosa anastomosis (WJ) and "dunking" pancreato-jejunal anastomosis (DPJ) are the two most used ones worldwide but conflicting results are reported. To determine which is the safer anastomosis and to define when an anastomosis should be preferred, we retrospectively reviewed two groups of patients who underwent WJ or DPJ. METHODS: Twenty-three patients underwent PD with WJ (n = 17) with dilated (WJD) (n = 9) or not-dilated Wirsung's duct (WJND) (n = 8) or with a DPJ (n = 6) over a 3-year period at a single institution. RESULTS: The complications rate was high in all groups of patients (33.3% in WJD, 37.5% in WJND and 66.7% in DPJ). A pancreatic fistula developed in one patient in each group (11.1% in WJD, 12.5% in WJND and 16.7% in DPJ). All these patients were managed conservatively. Anastomotic disruption took place in the WJ patients especially in the WJND group (n = 2) compared to the WJD (n = 1) (25% vs. 11.1%) or DPJ groups (0%): these three patients required a re-operation. Overall, the anastomotic defects were higher in patients who underwent WJND (37.5%), compared to WJD (22.2%) and to DPJ (16.7%). However, no statistical differences were found among the groups. Delayed gastric emptying (DGE) and total parenteral nutrition (TPN) along with anastomotic defects were responsible for a prolonged hospital stay. CONCLUSIONS: Our results were not able to demonstrate any statistical difference between the two different techniques in preventing anastomotic failure. WJ can represent a valid choice in case of a dilated duct and a firm, fibrotic enlarged gland that could not be properly invaginated in a small jejunal loop. DGE may occur in those patients who experienced an anastomotic failure and required a TPN regimen with a prolonged hospital stay.

Adult↗
PubMed2004

Indications and results of side-to-side isoperistaltic strictureplasty in Crohn's disease.

PURPOSE: Strictureplasty has commonly been used for short stenotic tracts, but it has rarely been applied to stenoses longer than 10 cm. Michelassi proposed a side-to-side isoperistaltic strictureplasty for single or multiple strictures that affected long bowel tracts. The experience and results obtained to date with this type of strictureplasty are limited. We therefore decided to review the cases in which we performed this procedure. METHODS: Thirty-one patients, aged 21 to 66 years, underwent this operation between August 1996 and October 2002. Indications for surgery included subocclusion in 22 patients, malnutrition in 9 patients, and fistula or abscess in 6 patients. Two side-to-side isoperistaltic strictureplasties have been performed in jejunum, 6 in jejunum-ileum, 16 in the proximal ileum, 1 in terminal ileum, and 6 in the ileo-cecal tract. RESULTS: The average length of side-to-side isoperistaltic strictureplasty as 32.1 cm (range, 10-54 cm). Sixteen patients also underwent concomitant bowel resection and 17 patients have received additional strictureplasty. There was no perioperative mortality, nor were there any postoperative complications requiring reoperation. In all patients intestinal occlusion and malnutrition were resolved. Decrease of activity indices was observed in 62.3 percent of patients within 6 months after surgery. At an average follow-up of 26.4 months, six patients required reoperation, but in only one of them did the recurrence involve a previous strictureplasty site. In that case the side-to-side isoperistaltic strictureplasty was soft and was without signs of inflammation or stenosis. CONCLUSIONS: Side-to-side isoperistaltic strictureplasty seems to provide a technical solution leading to improvement when long intestinal inflamed tract are treated. Longer follow-up and larger experience is needed to validate this observation.

Adult↗
PubMed2004

Selective oestrogen receptor modulators in desmoid tumours.

Selective oestrogen receptor modulators (SERMs) are compounds with a mixed agonist/antagonist activity on oestrogen receptors. An ideal SERM is a compound with an oestrogen antagonist effect on the breast and uterus but oestrogen agonist effect on bone. Beside tamoxifen, a group of well-investigated SERMs is represented by raloxifene, LY-353381 (SERM3), EM-800 and CP-336156. On an empirical basis, tamoxifen has been used to pharmacologically treat desmoid tumours. Recently, raloxifene, a second-generation SERM, has been used in the treatment of familial adenomatous polyposis patients affected by desmoid tumour. The mechanisms through which these molecules affect desmoid tumour growth appear to be due, in part, to the fact that SERMs may act independently of oestrogen receptors. The knowledge of the molecular basis of SERM action will make the development of novel synthetic compounds with engineered tissue selectivity possible.

Animals↗
PubMed2004

Small diameter H-graft porta-caval shunt performed at different stages of liver disease.

BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and occlusion). To further investigate these assumptions, we retrospectively reviewed the results of partial porta-caval shunts performed at different stages of liver disease. METHODS: Twenty-nine cirrhotic patients underwent a partial porta-caval shunt with a ringed polytetrafluoroethylene interposition prosthesis of 8-mm (20 patients) or 10-mm (9 patients) in diameter. Pre and post-shunt porta-caval pressure was measured in all patients. Twelve patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%). Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively. Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval pressure gradient, reduced significantly using either 8- or 10-mm prosthesis. The overall early mortality and morbidity were 13.8% and 48% respectively. The early mortality and morbidity were different between patients of Child A and B when compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No patient re-bled early from varices. The overall late mortality and morbidity were 40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8% of the two groups of patients respectively; variceal re-bleeding occurred in 4 patients (16%). Encephalopathy occurred postoperatively in 5 patients (20%), acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at 3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate that partial porta-caval shunt with a small diameter interposition H-graft is an effective procedure for the treatment of variceal bleeding, as well as for the prevention of re-bleeding in patients of Child A and those of Child B, as an elective or emergency/urgency procedure, with a low rate of complications and encephalopathy. This technique could be used safely in patients with good liver function but they should be monitored closely because of the risk of shunt occlusion.

Aged↗
PubMed2003

Tropomyosin expression in the ileal pouch: a relationship with the development of pouchitis in ulcerative colitis.

OBJECTIVE: Human tropomyosin isoform 5 (hTM5) is a cytoskeletal protein expressed in normal epithelial cells, predominantly in the colon. An autoimmune response toward hTM5 has been reported in ulcerative colitis (UC). Whether hTM5 expression in the ileum is involved in pouchitis is unknown. We assessed hTM5 expression on ileal epithelial cells at surgery and subsequently on development of pouchitis in UC. METHODS: In a prospective longitudinal study, 28 UC patients undergoing ileal pouch procedures were included. Biopsy samples were taken from the rectum at surgery, as well as from the ileal pouch at surgery and at 6 months. The specimens were stained by immunoperoxidase using the anti-hTM5 monoclonal antibody CG3. Pouchitis was assessed by the Pouchitis Disease Activity Index and hTM5 expression on a scale of 0-3. RESULTS: At surgery, in rectal samples, hTM5 expression was strong in all epithelial cells including the luminal surface, whereas in ileal samples hTM5 was not expressed or focally expressed only in the goblet cells. At 6 months, the ileum was found to have undergone morphological changes, becoming similar to the colon and showing shortening or reduced number of villi. These changes were associated with a diffuse hTM5 staining in the goblet cells and in the nongoblet epithelial cells lining the crypts and the lumen. The hTM5 score was related to the Pouchitis Disease Activity Index at 6 months (r = 0.82; p = 0.01). CONCLUSIONS: Expression of hTM5 shows a different pattern in the ileal pouch in UC after surgery. This event is associated with morphological changes of the ileum toward colonic epithelium, related to the development of pouchitis.

Antibodies, Monoclonal↗
PubMed2003

The rational principles of neo-adjuvant therapy for rectal cancer.

BACKGROUND: Aim of the study is to analyze rational principles which at present govern the neoadjuvant therapy for rectal cancer and justify his application. First step is definition of targets: cellular replication block, volumetric reduction of rectal cancer, mesorectum and lateral nodes (Down staging), reduction of side-effects on close organs, radiation on more limited tissue volumes, major series of sphincter saving procedures, minor risk of microscopic tumour deposits. Second step regards standards which Protocols strive in order to: patients selection, therapeutic index, restaging before surgery, total mesorectal excision (TME). Further step accounts for evidence of drawbacks, related to Neoadjuvant approach, both Radiotherapy alone (RT) or Radiochemotherapy (CH-RT). METHODS: Indications for neoadjuvant therapy, basing a difference between the absolute and relative one, are explained. Given that granting role to such therapy still now remain partially unclear, we have outlined the following topics: A) survey of main protocols is managed, taking care on dose/response ratio, focusing on enhanced supply for fixed tumours, checking on a list of several drugs (oxaliplatinum, capecitabin, raltitrexed, CPT-11, eniluracil), which are medicated with RT and furthermore on a list of substitute RT methods (HART, IORT, Endocavitary). B) following whole treatments, according such a different approaches, analysis of obtained outcomes in the literature are carried out. C) Personal experience, basing on a previous series where Down-staging has been sought, comparing indicatively clinical and diagnostic data before neoadjuvant therapy and before surgery. D) List of open issues, not solved at present, is shown CONCLUSIONS: Neoadjuvant therapy may be considered a rational approach for treatment of curative rectal cancer; indeed, preliminary results seem to introduce a real advantage compared to adjuvant therapy, even if is mandatory to associate proper surgical procedure, as TME, to warrant low local recurrences. Targets, related to such therapy, may be noticed ideal even though outcomes don't come up always to statements. So, continuous efforts to ameliorate rates of free-disease series, as well mortality rates and toxical effects are advised.

Chemotherapy, Adjuvant↗