Claudio Coco

Professor of Surgery
Head of general surgery division
Catholic University of the Sac... · Surgical Sciences Department

Publications

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    ABSTRACT: Perineal wounds after complete proctectomy are at risk for failure, with dramatic consequences on patients' health and quality of life. This study is aimed at identifying risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy.
    International Journal of Colorectal Disease 11/2014; · 2.24 Impact Factor
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    ABSTRACT: Ulcerative colitis (UC) is an inflammatory bowel disease affecting large bowel with variable clinical course. The history of disease has been modified by the introduction of biologic therapy, in particular Infliximab (IFX), that has demonstrated efficacy in inducing fast symptoms remission, promoting mucosal healing and maintaining long-term remission. However, surgery is still needed for UC patients: in case of failure of medical therapy and if acute complications or a malignancy occurred. Surgical treatment is associated with a short-term post-operative mortality and morbidity respectively of 0%-4% and 30%. In this study we systematically analyzed: the role of IFX in reducing the colectomy rate, the risk of post-operative morbidity in pre-operatively IFX-treated patients and the cost-effectiveness of IFX therapy. Four of 5 analyzed randomized controlled trials demonstrated that therapy with IFX significantly reduces the colectomy rate. Moreover, pre-operative treatment with IFX doesn't seem to increase post-operative infectious complications. By an economic point of view, the cost-effectiveness of IFX-therapy was demonstrated for UC patients suffering from moderate to severe UC in a study based on a cost estimation of the National Health Service of England and Wales. However, the argument is debated.
    World Journal of Gastroenterology 05/2014; 20(17):4839-4845. · 2.55 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the effect of neoadjuvant chemoradiotherapy on the lymph node yield of rectal cancer surgery. Data for patients who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from June 1992 to June 2009 were reviewed. The primary outcomes measured were the number of lymph nodes retrieved, their status, and patient survival. In total, 345 patients underwent neoadjuvant chemoradiotherapy followed by surgery, and 95 patients had surgery alone. Neoadjuvant chemoradiotherapy decreased both the median (range) number of lymph nodes retrieved (7 (1-33) versus 12·5 (0-44) respectively; P < 0·001) and the number of positive lymph nodes (0 (0-11) versus 0 (0-16); P = 0·001). After neoadjuvant chemoradiotherapy, the number of retrieved lymph nodes was inversely correlated with tumour regression, and with the interval between treatment and surgery. The 5-year overall and disease-free survival rates were 86·5 and 79·1 per cent respectively. After neoadjuvant therapy, lymph node status was found to be an independent predictor of survival, whereas the number of retrieved lymph nodes did not represent a prognostic factor for either overall or disease-free survival. Low lymph node count after neoadjuvant chemoradiotherapy for rectal cancer does not signify an inadequate resection or understaging, but represents an increased sensitivity to the treatment.
    British Journal of Surgery 01/2014; 101(2):133-42. · 4.84 Impact Factor
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    ABSTRACT: Transanal local excision has been suggested as an attractive approach for patients with rectal cancer who show a major clinical response after preoperative chemoradiotherapy. To evaluate the impact of transanal local excision on the local recurrence of rectal cancer in patients who had a major clinical response after preoperative chemoradiotherapy. Sequential 2-stage phase II study for early efficacy. Multicenter study. Patients with clinical T3 or low-lying T2 rectal adenocarcinoma that showed a major clinical response after a preoperative chemoradiotherapy. Eligible patients underwent a full-thickness transanal local excision. According to their histopathology, the patients staged as ypT0-1 were observed, while the remaining patients were recommended to undergo a subsequent total mesorectal excision. A local recurrence rate of ≤5% was set as a successful rate for stopping the trial early after the first stage. The study group included 63 patients. Before chemoradiotherapy, patients were staged as clinical T3 (n = 42) and T2 (n = 21). After the local excision, 43 patients fulfilled the criteria to be observed with no further treatment. Nine of the remaining 20 patients for whom a subsequent total mesorectal excision was recommended refused surgery. Two of these patients who refused surgery had intraluminal local recurrence; both had a ypT2 tumor and underwent salvage surgery. The estimated cumulative 3-year overall survival, disease-free survival and local disease-free survival were 91.5% (95% CI: 75.9-97.2), 91.0% (95% CI: 77.0-96.6) and 96.9% (95% CI: 80.3-99.5), respectively. The time of follow-up is still short and the sample size is limited. Our data suggest that local excision is a good option for patients with a major clinical response after chemoradiotherapy. A longer period of follow-up is required to confirm these findings.
    Diseases of the Colon & Rectum 12/2013; 56(12):1349-56. · 3.34 Impact Factor
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    ABSTRACT: Voltage-dependent type 7 K(+) (KV7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of KV7 channel modulators and the expression of KV7 channels in the human taenia coli. The effects of KV7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localization of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the KV7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC50 and Emax of 18.7μM and 30.5% of the maximal bethanechol-induced contraction, respectively. The KV7 channel activators retigabine and flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2μM and 29.9μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the KV7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli, with KCNQ4 showing the highest expression levels. KV7.4 channels were clearly visualized by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. KV7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, KV7 channel activators significantly relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
    European journal of pharmacology 10/2013; · 2.59 Impact Factor
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    ABSTRACT: BACKGROUND: Transanal endoscopic microsurgery (TEM) after radiochemotherapy (RCT) has been reported in selected cases of locally advanced rectal cancer as an alternative to traditional radical resection with total mesorectal excision with a curative intent or as diagnostic tool to confirm a pathological complete response of the primary tumor. No study has evaluated functional outcome after TEM in preoperatively irradiated patients. METHODS: This study was designed to evaluate short-term morbidity (according to Clavien's classifications) and establish (by a questionnaire) continence and evacuative function after RCT and TEM, at 1 year from surgery, analyzing the impact of RCT on postoperative outcomes. Patients with locally advanced rectal cancer treated by RCT and TEM (group 1) or with early T1 or adenomas treated only by TEM (group 2) entered this cohort comparative study. RESULTS: Twenty-two patients entered the study as group 1 and 25 as group 2. No postoperative mortality occurred. The morbidity rate was 36.4 % in group 1 vs. 16 % in group 2 (p = 0.114). The rate of suture dehiscence was 22.7 % in group 1 vs. 4 % in group 2 (p = 0.068). No grade III complications, reoperation, or hospital readmission within 30 days was recorded in either group. One year after surgery, continence and evacuative scores in group 1 were 1.05 ± 1.25 and 24.72 ± 2.79, respectively, which were similar to group 2 (p = 0.081 and 0.288, respectively). CONCLUSIONS: TEM after RCT in selected rectal cancer patients has an acceptable morbidity and functional results at 1 year from surgery. Preoperative irradiation could increase postoperative short-term morbidity, but it does not seem to influence evacuative or sphincter function after 1 year from surgery.
    Surgical Endoscopy 02/2013; · 3.43 Impact Factor
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    ABSTRACT: BACKGROUND: Expression levels of CD133, a cancer stem cell marker, and of the alpha-subunit of the dystroglycan (alpha-DG) complex, have been previously reported to be altered in colorectal cancers. METHODS: Expression levels of CD133 and alpha-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. RESULTS: Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0--80). A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002) and overall (p = 0.008) survival.Expression of alpha-DG was reduced in a significant fraction of tumors but low alpha-DG staining did not correlated with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in alpha-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between for both disease-free (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but not loss of alpha-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002) and death (RR = 2.3; p = 0.003). CONCLUSIONS: Loss of alpha-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.
    Journal of Experimental & Clinical Cancer Research 09/2012; 31(1):71. · 3.07 Impact Factor
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    ABSTRACT: Colorectal cancer is one of the deadliest diseases in Western countries. To predict the outcome of therapy, we assessed the role of class III (TUBB3) and class V β-tubulin (TUBB6) as predictive biomarkers. Using immunohistochemistry and nanofluidics, the expression of TUBB3 and TUBB6 was assessed in two cohorts of 180 and 134 patients, respectively. The CYP17A1 RS743572 was genotyped to identify GG carriers with enhanced androgen levels. TUBB3 and TUBB6 were investigated in 22 colorectal cancer cell lines in basal conditions and after serum starvation, the latter serving as activator of this prosurvival pathway. To ascertain the role of androgen receptor (AR) in such regulation, we silenced AR and checked TUBB3 and TUBB6 expression and sensitivity to chemotherapy. There was a link between poor survival, the expression of TUBB3/TUBB6, and AR only in females. Conversely, only in males carriers of the GG phenotype exhibited the worst outcome. Importantly, male cell lines were resistant to serum starvation and exhibited higher levels of TUBB6, thereby suggesting that the pathway is activated by androgens. In female cells this phenomenon was absent. In both genders, AR was the main driver of TUBB3/TUBB6 expression, as constitutive silencing of AR was associated with downregulation of TUBB3/TUBB6 expression and increased sensitivity to oxaliplatin and SN-38. The involvement of androgens in the TUBB3 pathway opens the way for clinical trials to assess the efficacy of antiandrogens for increasing the efficacy of chemotherapy in male colorectal cancer patients.
    Clinical Cancer Research 03/2012; 18(10):2964-75. · 7.84 Impact Factor
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    Advances in Endoscopic Surgery, 11/2011; , ISBN: 978-953-307-717-8
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    ABSTRACT: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T(2)- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm(2)/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Low pretreatment ADCs (<1.0 × 10(-3)mm(2)/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10(-3)mm(2)/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT.
    International journal of radiation oncology, biology, physics 11/2011; 83(2):594-9. · 4.59 Impact Factor
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    ABSTRACT: The past decade has seen significant advances in the evaluation of the small bowel, long considered as the "black box" in gastroenterology. The development of several endoscopic techniques, including capsule endoscopy (CE) and double (DBE)- and single (SBE)-balloon enteroscopy, has improved the evaluation of this part of the gut and led to reach a more precise preoperative diagnosis of small-bowel tumors. These rare tumors were previously diagnosed only after laparotomy, although laparoscopic advanced surgery can be used for minimally invasive therapeutic approach in these patients. This study was designed to evaluate the diagnostic and therapeutic impact of endoscopic procedures on small-bowel tumors. During October 2010, 148 SBE procedures were performed; in 14 patients (7 males and 7 females, mean age 58.8 years; range 37-82 years) who suffered from obscure gastrointestinal bleeding, with previous negative upper and lower GI endoscopy, a diagnosis of small-bowel tumor was suspected according to CT scan (7 cases) and/or CE (11 patients). Then, an enteroscopy was performed. Multiple biopsies were taken in 9 cases; endoscopic tattoos were performed in 11 cases. After endoscopic procedures, histological examination showed melanoma in one case, adenocarcinoma in seven, and adenoma in one case. In 11 of 14 patients, a laparoscopic partial resection of small bowel involved was possible due to endoscopic tattoos. In one patient, the involvement of colic segment precluded a laparoscopic resection. In two patients, the laparoscopic resection was not possible for technical problems. Histological findings on resected specimens were indicative for melanoma in one case, gastrointestinal stromal tumor (GIST) in four cases, gastrointestinal autonomic nerve tumor (GANT) in one case, adenoma in one, and adenocarcinoma in seven cases. New development of different endoscopic approaches to the small bowel has led to reach an earlier diagnosis of small-bowel tumors and a preoperative diagnosis with consequent minimally invasive surgical approach.
    Surgical Endoscopy 09/2011; 26(2):438-41. · 3.43 Impact Factor
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    ABSTRACT: The impact of preoperative use of TNF-alpha inhibitors on postoperative complications in patients with inflammatory bowel disease (IBD) undergoing abdominal surgery is controversial. The aim of this study was to evaluate the 30-day postoperative outcomes for IBD patients treated with these drugs prior to surgery. We analyzed retrospectively the incidence of short-term postoperative complications. Statistical analyses were performed to reveal the independent variables that influenced postoperative complications and the role of preoperative medical therapy with anti-TNF drugs within 12 weeks prior to surgery. One hundred fourteen patients (76 with Crohn's disease (CD) and 38 ulcerative colitis (UC)) underwent abdominal surgery for IBD. Fifty-four patients were treated with anti-TNF-alpha within 12 weeks prior to surgery (anti-TNF group). Postoperative mortality and morbidity were 0% and 21%, respectively. The infection rate was 15%. A significantly higher incidence of postoperative complications was found in patients treated with high-dose steroids (58% vs. 17%; p = 0.003) after univariate analysis. The infection rate was significantly higher in patients treated with high-dose corticosteroids (50% vs. 11%; p = 0.002) and concomitant anti-TNF-alpha (60% vs. 13%; p = 0.023). Multivariate analysis revealed that only therapy with high-dose corticosteroids was significantly associated with cumulative (p = 0.017) and infective postoperative complications (p = 0.046). No significant differences were found between the anti-TNF group and the control group. High-dose corticosteroids increased the risk of short-term postoperative cumulative and infective complications. Anti-TNF drugs within 12 weeks prior to abdominal surgery in patients with IBD did not appear to increase the rate of postoperative complications.
    International Journal of Colorectal Disease 05/2011; 26(11):1435-44. · 2.24 Impact Factor
  • Digestive and Liver Disease 10/2010; 43(2):171. · 3.16 Impact Factor
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    ABSTRACT: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.
    Techniques in Coloproctology 09/2010; 14(3):229-35. · 1.54 Impact Factor
  • Tecniques in Coloproctology. 07/2010; 14:229-235.
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    ABSTRACT: Small intestinal neoplasms are uncommon cancers. Benign small intestinal tumors (e.g., leiomyoma, lipoma, hamartoma, or desmoid tumor) usually are asymptomatic but may present with complications. Primary malignancies of the small intestine, including adenocarcinoma, leiomyosarcoma, carcinoid, and lymphoma, are often symptomatic and may present with intestinal obstruction, jaundice, bleeding, or pain. Metastatic neoplasms may involve the small intestine via contiguous spread, peritoneal metastases or hematogenous metastases. Because the small intestine is relatively inaccessible to routine endoscopy, diagnosis of small intestinal neoplasms is often delayed for months after onset of symptoms. During last years the increase of small bowel endoscopy and other diagnostic tools allow earlier non-operative diagnosis. Even though radical resection of small bowel cancer plays an important role, the 5 yr overall survival remains low.
    European review for medical and pharmacological sciences 04/2010; 14(4):327-33. · 1.09 Impact Factor
  • Digestive and Liver Disease 03/2010; 42. · 3.16 Impact Factor
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    ABSTRACT: The CD133 molecule has been proposed as a surface marker of cancer stem cells in several human malignancies, including colon cancers. The function and the mechanisms regulating CD133 expression remain unknown. The HT29 human colon cancer cells undergo differentiation following treatment with various agents and represent a useful in vitro model of colon differentiation. This study evaluated the behavior of CD133 during sodium butyrate-induced differentiation of HT29 cells. Treatment with sodium butyrate induced a progressive decrease of CD133 expression, as assessed by flow cytometry using the AC133 monoclonal antibody. Indeed, expression of CD133, which was about 47% in untreated control cells, gradually decreased down to about 3% after 72 h in a time- and dose-dependent manner. No relationship was observed between CD133 protein evaluated by flow cytometry and mRNA expression level, and no changes were detected in the methylation status of the CD133 gene promoter during HT29 differentiation. Moreover, the expression of the CD133 protein, evaluated by Western blot analysis using a specific anti-CD133 antibody directed against the C-terminal intracytoplasmic region of human CD133 protein, did not correlate with flow cytometry results. Different results were also obtained using the two antibodies to analyze the expression of the CD133 molecule in human colon cancers. These findings demonstrate that membrane expression of the CD133 stem cell marker might undergo a complex regulation during differentiation of colon cells and suggest that HT29 cells are a useful in vitro model to study the mechanisms involved in this regulation which likely occurs at a post-transcriptional level.
    Journal of Cellular Physiology 03/2010; 224(1):234-41. · 4.22 Impact Factor
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    ABSTRACT: Although surgery remains the most important treatment of rectal cancer, the management of this disease has evolved to become more multidisciplinary to offer the best clinical outcome. The International Conference on Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) had the duty to identify the degree of consensus that could be achieved across a wide range of topics relating to the management of rectal cancer helping shape future programs, investigational protocols and guidelines for staging and treatment throughout Europe. Consensus was achieved using the Delphi method. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by topic, and a series of statements were developed. Each committee member commented and voted, sentence by sentence three times. Sentences which did not reach agreement after voting round #2 were openly debated during the Conference in Perugia (Italy) December 2008. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", "minimum consensus". The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of members. All chapters were voted on by at least 75% of the members, and the majority was voted on by 85%. This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe. In spite of substantial progress, many research challenges remain.
    Acta chirurgica iugoslavica 01/2010; 57(3):9-16.
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    ABSTRACT: In recent years, preoperative therapy has become standard procedure for locally advanced rectal cancer. Tumor shrinkage due to preoperative chemotherapy-radiation therapy (CRT) is now a reality, and pathologically complete responses are not uncommon. Some researchers are now addressing organ preservation, thus increasing the demand for both functional and morphologic radiologic evaluation of response to CRT to distinguish responding from nonresponding tumors. On magnetic resonance (MR) images, post-CRT tumor morphologic features and volume changes have a high positive predictive value but a low negative predictive value for assessing response. Preliminary results indicate that diffusion-weighted MR imaging, especially at high b values, would be effective for prediction of treatment outcome and for early detection of tumor response. Some authors have reported that the use of apparent diffusion coefficient values in combination with other MR imaging criteria significantly improves discrimination between malignant and benign lymph nodes. Sequential determination of fluorodeoxyglucose uptake at positron emission tomography/computed tomography has proved useful in differentiating responding from nonresponding tumors during and at the end of CRT. However, radionuclide techniques have limitations, such as low spatial resolution and high cost. Large studies will be needed to verify the most effective morphologic and functional imaging modalities for post-CRT restaging of rectal cancer. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.303095085/-/DC1.
    Radiographics 01/2010; 30(3):699-716. · 2.79 Impact Factor

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