Screening for oral cancer utilising risk-factor analysis is ineffective in high-risk populations.

Screening for oral cancer by direct visual examination is believed to be ineffective because of the difficulty in differentiating a small number of malignancies from the much more prevalent benign oral mucosal lesions (OML) that are found in high-risk individuals. Standardised clinical diagnoses were recorded for all the OMLs identified during oral visual examination of 1111 individuals with risk factors for oral cancer, including tobacco and areca nut (paan) consumption. Suspicious lesions were referred for biopsy and definitive diagnosis. A total of 1438 OMLs with 32 different clinical diagnoses were identified in 604 participants. Analysis of referrals revealed two distinct groups: visually benign lesions (VBLs) none of which was referred, and visually complex lesions (VCLs) comprising 661 OMLs with nine different clinical diagnoses. After biopsy the VCLs included known potentially malignant disorders (PMDs) as well as benign lesions such as paan mucositis. VCLs (but not VBLs) share risk factors with oral cancer (p<0.05 for paan 5.82 (CI: 1.98 to 8.43), and smoking 3.59 (CI: 1.12 to 4.47)). They are clinically indistinguishable from, but much more prevalent than, oral cancer, and most will never undergo malignant change. They therefore can prevent dentists from accurately detecting malignancy during the clinical examination of high-risk patients. However, they can easily be differentiated from other benign lesions by visual examination alone. Further research into diagnostic technology is needed to help differentiate them from oral cancers.

Osteonecrosis and osteomyelitis of the jaw associated with tumour necrosis factor-alpha (TNF-α) inhibitors: a systematic review.

Tumour necrosis factor-α (TNF-α) inhibitors are increasingly being used as immunomodulators to manage inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Reported serious side effects include an increased incidence of lymphoma and greater susceptibility to infections such as tuberculosis. The aim of this systematic review was to find out whether there is an associated risk of medication-related osteonecrosis of the jaw (MRONJ). Three authors independently searched PubMed, MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials for published reports of oral osteonecrosis (ONJ) or osteomyelitis (OM) in patients who took anti TNF-α drugs and had no history of antiangiogenic agents or antiresorptive treatment. All types of studies on humans treated with TNF-α inhibitors were considered. Only six were eligible for analysis, and all were independently assessed for risk of bias. They included six patients with ONJ or OM that was attributed solely to TNF-α inhibitors. The most common site of ONJ was the posterior mandible (n=5). The mean (SD) duration of anti-TNF-α treatment before the development of bony lesions was 62.5 (47.4) months. Invasive surgery was reported as a precipitating factor in five cases, and the ONJ/OM resolved with conservative management in five. Although all the studies were judged to be at high risk of bias, the limited data suggest that some patients will potentially develop ONJ/OM as a result of treatment with TNF-α inhibitors. Studies of higher quality are now needed to establish the relative risk of MRONJ in patients who take them.

Modelling clinical decision-making in triage of referrals for extraction.

Introduction: Oral surgery services are progressively moving out of traditional hospital departments and into primary care. This necessitates accurate methods of triaging referrals, so patients of varying complexity are managed in the most suitable environment. The latest NHS commissioning proposal identifies 'level 1' procedures as simple extractions which do not require referral. We developed a model for quantifying how accurately these simple extractions can be predicted from information in standard referral letters. Methods: Experienced clinicians (N = 10) were independently asked to predict whether extractions (N = 25) were likely to be simple-forceps or surgical procedures, from information provided in specially developed standardised referral letters. One oral surgeon had previously completed all extractions. The triaging clinicians were asked to comment on reasons for each decision and state their level of confidence in their predictions. Results: Only 67% (range 52­76%) of extractions were correctly predicted as either simple or surgical with a significant propensity to underestimate the complexity of surgical extractions rather than overestimating simple procedures (p <0.05). High levels of confidence reported by the clinicians in their decisions correlated with more accurate predictions (p <0.05). Conclusions: This is the first attempt to develop a model for clinical decision-making in oral surgery triage services. Our findings suggest there is significant scope for improvement and highlight areas for development.

Oral cancer screening in the Bangladeshi community of Tower Hamlets: a social model.

BACKGROUND: UK oral cancer incidence has risen by 22% in the last 10 years. Oral cancer is often detected at a late stage when treatment is debilitating and the chances of survival are poor. Certain black and minority ethnic groups are at elevated risk of oral cancer due to the prevalence of risk factor behaviours. We describe the background to, the development of and outcomes of an oral cancer screening activity appropriate to the needs of members of a disadvantaged community at high risk of oral cancer, carried out between 2006 and 2008 in Tower Hamlets, East London. METHODS: In all, 1320 people participated during 34 days of screening, divided into two phases (Phase I (2006/2007): n=485, Phase II (2008): n=835). Modifications to the delivery process were implemented for Phase II in an attempt to recruit more high-risk individuals and to improve screening specificity. RESULTS: In total, 75 people were urgently referred for further investigation (Phase I: n=20, Phase II: n= 55). Nine were diagnosed with dysplastic lesions (Phase I: n=3, Phase II: n=6) and a further eight showed potentially malignant disorders without dysplasia (Phase I: n=1, Phase II: n=7). Screening participants with low levels of completed education (OR: 6.94, 95% CI: 1.66, 28.98) and who chewed paan with tobacco (OR: 8.01, 95% CI: 3.54, 18.08) were more likely to be referred for further investigation. CONCLUSION: The project offers insights for the further development of oral cancer screening interventions for disadvantaged communities.

The CAP-CR study: direct medical costs in Italian metastatic colorectal cancer patients on first-line infusional 5-fluorouracil or oral capecitabine.

AIM: To describe the healthcare resource consumption of metastatic colorectal cancer (MCRC) patients in the Italian healthcare setting. METHODS: A retrospective chart analysis estimating direct medical costs of first-line infusional 5-Fluorouracil (5-FU) or oral Capecitabine (CAP), associated or not with other chemotherapies, from the Italian Healthcare Service (IHCS) and Hospital (H) perspectives. RESULTS: 202 subjects were analysed. CAP patients (N=66) were older, with a more compromised clinical status and received less chemotherapy agents in association than 5-FU patients (N=136). From the IHCS perspective, mean total costs per patient were 12,029 euro and 5,781 euro in the 5-FU and CAP arms respectively; 7,338 euro and 4,688 euro from the H perspective. The infusional administration route of 5-FU was a cost driver from both perspectives. Sensitivity analyses found the results to be robust to variations in base case parameters. CONCLUSIONS: Management of MCRC by oral chemotherapies may be an economically advantageous option to both IHCS and hospitals.

Fingerprinting genomic instability in oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a high-risk pre-cancerous condition where 7-13% of these patients develop head and neck squamous cell carcinoma (HNSCC). To date there is no cancer predictive markers for OSF patients. Genomic instability hallmarks early genetic events during malignant transformation causing loss of heterozygosity (LOH) and chromosomal copy number abnormality. However, to date there is no study on genomic instability in OSF. Although this condition is known as a high-risk pre-cancerous condition, there is no data regarding the genomic status of this disease in terms of genetic susceptibility to malignant transformation. METHODS: In this study, we investigated the existence of genetic signatures for carcinogenesis in OSF. We employed the high-resolution genome-wide Affymetrix Mapping single nucleotide polymorphism microarray technique to 'fingerprint' global genomic instability in the form of LOH in 15 patient-matched OSF-blood genomic DNA samples. RESULTS: This rapid high-resolution mapping technique has revealed for the first time that a small number of discrete hot-spot LOH loci appeared in 47-53% of the OSF tissues studied. Many of these LOH loci were previously identified regions of genomic instability associated with carcinogenesis of the HNSCC. CONCLUSION: To our knowledge, this is the first evidence that genomic instability in the form of LOH is present in OSF. We hypothesize that the genomic instability detected in OSF may play an important role in malignant transformation. Further functional association studies on these putative genes may reveal potential predictive oral cancer markers for OSF patients.

Upregulation of HIF-1alpha in malignant transformation of oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a precancerous condition showing extensive fibrosis of the submucosa and affects most parts of the oral cavity, including pharynx and upper third of the oesophagus. The molecules involved in the biological pathways of the fibrotic process appeared to be either down- or upregulated at different stages of the disease. Despite the precancerous nature, malignant transformation of the epithelium in the background of fibrosis has not been studied in detail. HIF-1alpha is a known transcription factor that is induced by hypoxia. AIMS: To test the hypothesis that hypoxia plays a role in malignant transformation and progression of OSF. MATERIALS AND METHODS: We used both formalin-fixed and frozen samples of OSF and normal mucosa to investigate the relationship between HIF-1alpha and epithelial dysplasia using immunohistochemistry and RT-PCR. CONCLUSIONS: Our data indicate that HIF-1alpha is upregulated at both protein and mRNA levels in OSF and the correlation with epithelial dysplasia is statistically significant (P < 0.001). We propose that HIF-1alpha may play a role in malignant transformation of OSF. Further, over-expression of HIF-1alpha may contribute to the progression of fibrosis. It may be possible to use HIF-1alpha as a marker for malignant transformation of OSF.

Expression of cytokeratins, adhesion and activation molecules in oral ulcers of Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystemic inflammatory disorder of which oral aphthous ulceration is a major feature. AIMS/HYPOTHESIS. This study sought to determine the role of cytokeratins, differentiation and proliferation markers, gammadelta T-cell adhesion and activation molecules, and apoptotic markers in oral ulcers of this disease. METHODS: Expression patterns for cytokeratins (K1, K6, K14, K15, K16), integrins (beta1 and alpha6), CD3 T-cell and gammadelta T-cell adhesion and activation markers [CD40, CD44, CD54, ICAM-1, CD58, leucocyte function-associated antigen (LFA)-3, vascular cell adhesion molecule-1 (VCAM-1), CD86], and cellular proliferation and differentiation markers (Ki67 and involucrin), and apoptotic markers (CD95 and Bcl-2) in oral ulcers of nine patients with BD and four healthy controls were analysed by immunohistochemistry. RESULTS: K14, K15 and involucrin expression were unchanged, whereas Ki67, the proliferation marker, was reduced by around 50%. K1, K6, K16, beta1 integrin and the apoptotic marker CD95 were upregulated, whereas alpha6 integrin and Bcl-2 were downregulated in BD samples. CD3 and gammadelta T-cell expression and other adhesion molecules including CD44, CD86, CD58 (LFA-3), VCAM-1 and intercellular adhesion molecule-1 (CD54) were upregulated, whereas CD40 showed little change. CONCLUSIONS: Our data demonstrates changes in cell-cell and cell-extracellular matrix interactions that affect cell homeostasis and may participate in the formation of oral ulcers in BD.

Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer pretreated with FOLFOX.

This multicentre phase II study was designed to evaluate the antitumour activity and toxicity of bifractionated camptothecin (CPT-11) and 5-fluorouracil/ leucovorin (5-FU/LV) in the treatment of patients with metastatic colorectal cancer (MCC) who had been pretreated with 5-FU/LV-oxaliplatin (FOLFOX regimen). In all, 35 patients were enrolled in a two-stage trial. Treatment consisted of two daily doses of CPT-11, 90 mg m2 administered over 90 min, followed by LV, 200 mg m2 administered over 2 h plus 5-FU 400 mg m2 as a bolus and 600 mg m2 as a 22-h continuous infusion administered with disposable pumps as outpatient therapy. Toxicity was closely monitored. Response was evaluated by computed tomography scans every 8 weeks. All 35 patients were assessable for toxicity and response to treatment. Seven patients had a partial response, giving an overall response rate of 20%; 11 patients had stable disease (31.4%) and 17 progressed (48.5%). The median progression-free survival was 7.1 months and median survival was 14 months. A total of 10 patients (30%) experienced grade 3-4 toxicity, including nausea (15%), diarrhoea (12%) and neutropenia (15%), while seven patients (21%) had grade 2 alopecia. The bifractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed substantial antitumour activity and was well tolerated in this group of patients with a poor prognosis, pretreated with the FOLFOX regimen.

Multicenter phase II study of CPT-11 fractionated over two days with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer.

PURPOSE: This multicenter phase II study evaluated the activity and toxicity of the combination of fractionated camptothecin (CPT-11) and 5-fluorouracil/leucovorin (5-FU/LV) (de Gramont regimen) for the treatment of metastatic colorectal cancer (MCC) patients who had received no prior chemotherapy for metastatic disease. PATIENTS AND METHODS: Fifty-four patients with a median age of 63.5 years (range: 43-75), received, every two weeks, a regimen consisting of 2 daily doses of CPT-11, 90 mg/m2 administered over a period of 90 minutes, followed by LV, 200 mg/m2 administered over 2 hours and 5-FU 400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour continuous infusion. Sixty-five percent of patients had synchronous metastatic disease at diagnosis, while 35% of the patients had received adjuvant chemotherapy after radical surgery. RESULTS: All 54 patients, receiving a total of 561 cycles of chemotherapy (median 12 per patient, range 1-26), were assessable for toxicity and response to treatment. The most common toxicities (grade 3-4) among treated patients were as follows: diarrhea in 3 patients, (6%), neutropenia in 9 patients (17%) and asthenia in 3 patients (6%), with no treatment-related death. We observed 4 complete (7.4%) and 18 partial responses (33.3%), giving an overall response rate of 40.7% (95% CI: 28% to 55%); 22 patients had stable disease (40.7%) and 10 patients progressed (18.5%). After a median follow-up of 22 months, the median time to progression was 8.7 months (range 2.3-43.9+), while overall median survival was 18.8 months (range 0.7-43.9+). CONCLUSION: The fractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed a lower gastrointestinal toxicity profile than expected, with substantial activity in patients with MCC.

Multicenter phase II study of fractionated bimonthly oxaliplatin with leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer, pre-treated with chemotherapy.

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.

Ifosfamide, cisplatin, and 13-Cis retinoic acid for patients with advanced or recurrent squamous cell carcinoma of the head and neck: a phase I-II study.

BACKGROUND: Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I-II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS: Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m(2) CDDP, and IFO was administered with sodium mercaptoethanesolfonate in three-dose increments (1000 mg/m(2), 1200 mg/m(2), and 1500 mg/m(2)) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS: Fifty-two patients either with locoregional recurrence or distant metastases (50%) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50%) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m(2). In the Phase II study (CDDP 20 mg/m(2) and IFO 1200 mg/m(2)), the response rate was 72% (95% confidence interval, 57-83%). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9-47.2+ months), and the median overall survival was 12.95 months (range, 1.7-47.2+ months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3-4 neutropenia was observed in 16 patients, and Grade 2-3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS: The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity.

Keratin 15 expression in stratified epithelia: downregulation in activated keratinocytes.

Keratin 15 (K15) is a type I keratin without a defined type II partner whose expression in epidermal diseases has not been investigated. In this study we have used LHK15, a monoclonal antibody raised against the last 17 amino acids of the K15 polypeptide, to show that K15 is expressed primarily in the basal keratinocytes of stratified tissues, including the fetal epidermis and fetal nail. Although K15 in normal hair follicles was virtually absent from hair bulbs, it was expressed by a subset of keratinocytes in the outer root sheath. By comparison, K14 expression was found throughout the outer root sheath of hair follicles; however, when both K14 alleles were naturally ablated, the expression of K15 was also observed throughout the outer root sheath of the follicles. Expression of K15 mRNA was assessed by in situ hybridization and corroborated the data from immunostaining. An increase in K15 mRNA and protein expression in hair follicles from the K14 ablated epidermis suggested an upregulation of the K15 gene in the absence of the K14 protein. In organotypical cultures where differentiating keratinocytes expressed markers of activated phenotype, i.e., K6 and K16, expression of K15 was undetectable. The expression of K15 mRNA and protein was also downregulated in two hyperproliferating situations, psoriasis and hypertrophic scars. Because keratinocytes in psoriasis and hypertrophic scars are activated, we conclude that K15 expression is not compatible with keratinocyte activation and the K15 gene is downregulated to maintain the activated phenotype.

Carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer: a phase II study.

The authors evaluated the efficacy and toxicity of the combination of carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer. From March 1994 through March 1996, 56 previously untreated patients with stage IIIB or stage IV non-small-cell lung cancer with measurable lesions and good performance status were entered in the study. The chemotherapy schedule was as follows: carboplatin 100 mg/m2 and ifosfamide 1,500 mg/m2 with mesna on days 1, 2, and 3; vinorelbine 25 mg/m2 on days 1 and 8, every 21 days; for a total of six courses. Among 55 evaluable patients there were three complete responses (5%) and 22 partial responses (40%), for a response rate of 45% (95% confidence interval, 32-59%). The median response duration was 10.3 months (range, 2.5-27.7 months), and median survival time was 11.3 months (range, 1.1-28.1 months). The survival rate at 1 year was 48%. Toxicity included hematologic toxicity in 60% of the 247 treatment cycles administered, nausea, alopecia, and neuropathy. One pathologic complete response was observed in a patient with stage IIIB disease who became operable after four courses of chemotherapy. The outpatient treatment with carboplatin, ifosfamide, and vinorelbine shows activity in advanced non-small-cell lung cancer. The toxicity was well tolerated by patients with a good performance status.

Activity of standard-dose carboplatin, cyclophosphamide, and etoposide in patients with metastatic breast cancer with previous exposure to anthracyclines.

The prognosis for patients with metastatic breast cancer, progressing after anthracycline-based cytotoxic therapy, is poor, and new treatment strategies are needed. Carboplatin (CBDCA), etoposide (VP-16), and cyclophosphamide (CTX) combination therapy has proved activity against a wide variety of tumors. This study was undertaken to evaluate the activity and toxicity of standard doses of CBDCA, VP-16, and CTX administered as salvage chemotherapy in a group of patients with metastatic breast cancer previously treated with two chemotherapy regimens, including anthracyclines. Thirty patients received an average 3.5 courses of the following treatment: CBDCA, 300 mg/m2, and CTX, 500 mg/m2, on day 1; VP-16, 60 mg/m2, on days 2, 3, and 4. Thirteen patients (43%) achieved an objective response, seven (23%) stabilized, while 10 (34%) progressed. The median response duration was 11.5 months (range, 1-19); the median overall survival from protocol entry was 9.1 months (range, 1.5-26). Gastrointestinal toxicity was noted in six patients, and hematologic toxicity of grade 3-4 was found in 11 patients. The combination of CTX, CBDCA, and VP-16 at this dose and schedule is active as salvage treatment of patients with breast cancer. Even when the toxicity was severe, responders had good symptom palliation with a substantial improvement in performance status.

Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer.

We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, to either a combination chemotherapy of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or the same regimen plus interferon. Between January 1990 and March 1992, 100 untreated patients (PTS) with advanced colorectal cancer, 53 men and 47 women, with an ECOG performance status (PS) of < or = 3, were randomized to either HDFA 200 mg/m2 iv bolus and 5FU 370 mg/m2 in 15-min iv infusion days 1-5 every 4 weeks (arm A), or the same chemotherapy plus IFN 3 x 10(6) IU subcutaneously three times a week in chemotherapy intervals (arm B). A total of 97 PTS are evaluable for response, toxicity, and survival; 3 PTS are not evaluable in arm B for major protocol violations. PTS characteristics were well balanced in both arms for age (median, 64 years), disease-free survival, and disease site. ECOG PS was 0 in 28% of PTS in arm A and in 13% in arm B. Response rates were as follows: arm A, 40%; and arm B, 23%. Median time to failure was as follows: 10.2 months arm A versus 9 months arm B. Median survival was as follows: 13.3 months arm A versus 10.9 months arm B. Grade 3 haematological toxicity was 9% of PTS in both arms. Gastrointestinal toxicity was as follows: 17% arm A versus 22% arm B. The cost of drugs expressed per m2/month was $60 in arm A and $390 in arm B. The results show that IFN at the schedule and doses employed adds no benefit to the combination of 5FU/HDFA.

[Computerized tomography and magnetic resonance in the diagnosis of recurrent rectal neoplasms: comparison of reliability and errors of both methods]. / Tomografia computerizzata e Risonanza Magnetica nella diagnosi di recidiva delle neoplasie del retto: affidabilità ed errori delle due metodiche a confronto.

Our work was aimed at assessing the accuracy of CT and MRI in the early identification of postoperative recurrences of rectosigmoid cancer, quantifying false positive and false negative ratios and questionable findings. A homogeneous series of 50 patients submitted to surgery for primary rectosigmoid carcinoma was studied with both CT and MRI and followed-up for up to 2 years: local recurrences were observed in 15 patients (30%) which occurred within the first year of surgery in 67% of cases and were in extraluminal site in 86% of cases. CT appeared to be a reliable and highly sensitive screening method, with 82% sensitivity: only 2 false negatives were observed, which were nevertheless followed-up because CT had yielded questionable, and not negative, findings. In contrast, CT had only 78% specificity, being unable to differentiate fibrosis, displaced normal structures and recurrences in 7 cases; its positive predictive value (PPV) was 66%, with 89% negative predictive value (NPV) and 80% accuracy. MRI had a complementary role to CT, because of its capabilities in discriminating all the questionable CT cases and in identifying all CT false positives, thanks to its higher specificity (100%). MRI had 74% sensitivity, which was lower than that of CT; MRI yielded 2 false negatives which, however, had been previously diagnosed with CT. MRI had 100% PPV, 89% NPV and 92% accuracy. Therefore, for the early detection of rectal cancer recurrences, the following diagnostic protocol is suggested: CT should be performed first, as a screening method, within 2-4 months of surgery, and repeated every 6-8 months during the first 2 years-together with CEA values monitoring. MRI should be reserved to the patients in whom CT findings were positive, questionable, or in disagreement with clinical symptoms and/or with increasing CEA values. If MRI fails to solve the diagnostic doubt, a CT-guided biopsy of the mass should be performed.