Systematic Resection of the Visible Scar After Incomplete Endoscopic Resection of Rectal Neuroendocrine Tumors.

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.

Precision Medicine in Pancreatic Ductal Adenocarcinoma: The Impact of Targeted Therapies on Survival of Patients Harboring Actionable Mutations.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. METHODS: We conducted a retrospective analysis of all patients, aged ≥18 years with histologically confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP). RESULTS: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 (18%)), HER2 (5 (18%)), MTAP (5 (18%)), and FGFR (3 (11%)). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n = 12 (11.8%)), 14 months in patients with actionable GAs treated with standard therapies (n = 17 (16.7%)), and 17 months in patients without actionable GAs treated with standard therapies (n = 73 (71.5%); p = 0.26). The absence of liver metastases was associated with better OS (HR = 0.471, p = 0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. INTERPRETATION: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

NF1-Associated Inflammatory Polyp of the Colon: First Report of a Sporadic Case.

"Juvenile-like (hyperplastic/inflammatory) mucosal polyp" is a term proposed for rare benign mesenchymal lesions of the gastro-intestinal tract so far reported only in patients with type 1 neurofibromatosis (NF1). We report here a first sporadic case of NF1-associated mucosal inflammatory polyp of the colon. The diagnosis was made in a 53-year old female patient with a large polypoid tumor of the cecum. The lesion was predominantly mucosal, made of fibroblast-like cells associated with inflammatory infiltrates rich in eosinophils and containing entrapped, distorted epithelial glands, responsible for the juvenile-like appearance. Whole exome sequencing showed a pathogenic variant of NF1. The patient had no evidence of NF1; no NF1 mutation was detected in normal tissues. Our observation may support the existence of juvenile-like inflammatory polyps associated with NF1 alterations, either germline or somatic. This justifies to test NF1 in difficult-to-classify gastrointestinal mesenchymal tumors.

Pulse-dose-rate interstitial brachytherapy in anal squamous cell carcinoma: clinical outcomes and patients' health quality perception.

PURPOSE: To examine clinical outcomes and quality of life of patients with anal squamous cell carcinoma treated with interstitial pulsed-dose-rate brachytherapy (PDR-BT) with a boost to residual tumor after external radiotherapy. MATERIAL AND METHODS: Medical records of patients receiving a brachytherapy boost after radiotherapy for anal squamous cell carcinoma in our Institute between 2008 and 2019 were retrospectively reviewed. After receiving pelvic irradiation ± concurrent chemotherapy, patients received PDR-BT boost to residual tumor, in order to deliver a minimal total dose of 60 Gy. Patients' outcomes were analyzed, with primary focus on local control, sphincter preservation, morbidity, and quality of life. RESULTS: A total of 42 patients were identified, included 24, 13, and 5 patients with I, II, and III tumor stages, respectively. Median brachytherapy (BT) dose was 20 Gy (range, 10-30 Gy). Median dose per pulse was 42 cGy (range, 37.5-50 cGy). With median follow-up of 60.4 months (range, 5.4-127.4 months), estimated local control and colostomy-free survival rates at 5 years were both 88.7% (95% CI: 67.4-96.4%). The largest axis of residual lesion after external beam radiation therapy (EBRT) and poor tumor shrinkage were associated with more frequent relapses (p = 0.02 and p = 0.007, respectively). Out of 40 patients with more than 6 months follow-up, only one experienced severe delayed toxicity (fecal incontinence). Health quality perception was very good or good in 20 of 22 (91%) patients, according to their replies of quality-of-life surveys. A total dose ≥ 63 Gy was associated with higher number of anorectal grade 1+ toxicities (n = 1.5 vs. n = 0.61, p = 0.02). CONCLUSIONS: In this cohort of 42 patients with mainly I and II tumor stages, PDR-BT boost allowed for local control in 88.7% of patients, with only one grade 3 anorectal toxicity.

Post-Radiation Grade 3 Neuroendocrine Carcinoma: A New Entity?

BACKGROUND: Cancer survivors have a 14% increased risk of developing a malignancy compared with the general population. Second radiation-induced malignancies with different histologies have been described in different organs. Based on individual observations, we hypothesized that neuroendocrine carcinoma (NEC) could arise in irradiated organs. METHODS: In a retrospective analysis of Gustave Roussy database of NEC patients (small cell lung cancer excluded) diagnosed as a second cancer, we looked for the frequency of grade 3 NEC that arose in patients who had received previous radiation therapy for a first cancer. Radiation therapy for the first cancer, dose, location of radiation therapy, pathological characteristics, overall survival, and response to treatment of secondary NEC were analyzed. RESULTS: From January 1995 to December 2017, 847 cases of NEC were seen at Gustave Roussy. Among them, 95 (11.2%) patients had a history of previous malignancy of which 36 (4%) had been treated with radiation therapy. Out of these 36 patients, 12 (1.4% of all NEC patients) developed a NEC within the previous irradiated organ (median dose of 50 Gy, range 36-67.5). Most frequent first cancers were breast cancer (n = 4) and Hodgkin lymphoma (n = 3). NEC arose within a median time of 21.7 years (range 5.1-36.4) from radiation in the thorax (n = 5), digestive tract (n = 3), and other sites. Five large cell NEC, 3 small cell NEC, 1 mixed neuroendocrine neoplasm and 3 not otherwise specified NEC were diagnosed. Ten patients had stage IV disease at diagnosis; median overall survival was 37.8 months (95% CI [17.6 to NA]). Three patients (25%) achieved complete response with multimodal treatment. CONCLUSIONS: NEC can arise from previously irradiated organs and may have a better outcome in this setting. Other risk factors should be investigated to explain the high rate of previous cancer in this population of neuroendocrine neoplasm.

Long-Term Results after Surgical Resection of Peritoneal Metastasis from Neuroendocrine Tumors.

INTRODUCTION: Peritoneal metastases from neuroendocrine tumors are associated with a bad prognosis. The objective of our study was to evaluate whether surgical resection could lead to prolonged survival in selected patients. This survival was compared to that of patients operated for liver metastasis. METHODS: From our prospectively maintained database we included 88 patients who underwent the complete resection of peritoneal and/or liver metastasis between January 1995 and December 2016 in Gustave-Roussy. Three resection groups were compared: peritoneal metastasis alone, liver metastasis alone, and the combined resection of liver and peritoneal metastases. RESULTS: The median peritoneal cancer index was 10 in the peritoneal group and 11 in the peritoneal + liver group. The 5-year overall survival was 81% (60-100) in the peritoneal group compared to 78% (65.2-92.8) in the liver group, and 72% (58.7-89.7) in the peritoneal + liver group (p = 0.71). The 3-year disease-free survival reached 26.9% (16.1-45.1) in the liver group, 12.5% (2.3-68.2) in the peritoneal group, and 32.4% (19.9-52.6) in the combined liver + peritoneal group (p = 0.45). In the univariate analysis, the prognosis factors for a longer survival were: small bowel primary tumor origin, low preoperative chromogranin A level, and tumor grade ≤1. CONCLUSION: Despite a high recurrence rate, long-term overall survival can be achieved after the resection of peritoneal metastasis in selected patients. This survival is comparable to that of patients operated for liver metastasis only. Surgery should stand as a standard treatment for peritoneal metastases in patients with resectable disease.

Palliation of dysphagia in metastatic oesogastric cancers: An international multidisciplinary position.

Malignant dysphagia is the most common symptom in advanced oesogastric cancers patients. Relief of dysphagia allows quality of life improvement, nutritional replenishment and potentially improves prognosis. Chemotherapy alone is effective and should be prioritised in patients with metastatic disease a good performance status, and its impact on dysphagia should be determined before further interventions are planned. Regarding local treatments, the insertion of a covered self-expandable metallic stent is the most commonly used alternative, as it allows for the rapid relief of severe dysphagia. Although several randomised trials have highlighted the role of oesophageal brachytherapy, this technique is often not easily accessible. Contemporary trials are ongoing to better define the role of external radiation therapy. While awaiting these results, external radiation therapy can be considered as a second-best option for patients with a life-expectancy > 3 months. It is important to offer nutritional support and to integrate quality of life measures in the palliative management of dysphagia. This multidisciplinary international position paper aims to propose a decision-making process and highlight randomised trials for the management of malignant dysphagia in metastatic oesogastric cancer patients.

Esophageal brachytherapy: Institut Gustave Roussy's experience.

PURPOSE: Esophageal cancer is characterized by its propension to local evolution, which conditions prognosis and quality of life. Brachytherapy may be a therapeutic option for all stages of esophageal cancer. METHODS AND MATERIALS: This retrospective unicentric study included all consecutive patients treated for an esophageal high-dose-rate brachytherapy in our institution from 1992 to 2018. RESULTS: Ninety patients were included. They were treated in four distinct indications: exclusive (7 patients), boost after external beam radiotherapy (41), reirradiation (36), or palliative aim (6). Most frequently prescribed schemes were 3 × 5 Gy (boost) or 6 × 5 Gy (exclusive treatment and reirradiation) at applicator's surface or at 5 mm. At the end of follow-up, 50% of patients had presented with local recurrence. Seventeen percent of patients had a metastatic relapse. Median overall survival was 15 months in the whole cohort: 22 months in the boost setting, 25 months for exclusive brachytherapy, 15 months for reirradiation, and only 2 months for palliative treatment. Tumor length at brachytherapy, brachytherapy dose, and interfraction response were significantly associated to overall survival. 40% of patients presented with grade 2+ toxicity, mostly esophagitis, including three toxic deaths. CONCLUSIONS: Although local control outcomes are still poor, one must remember that patients are unfit for any curative therapeutic option and that palliative chemotherapy offers mediocre results. The most promising setting probably is reirradiation because brachytherapy offers a remarkable dose gradient allowing best organ at risk sparing, with an encouraging rate of long survivors (19% at 2 years). Esophageal brachytherapy deserves to be further investigated because some patients, even unfit, may benefit from it, with acceptable toxicity.

Adenoma detection by Endocuff-assisted versus standard colonoscopy in routine practice: a cluster-randomised crossover trial.

OBJECTIVE: Endocuff Vision (ECV) is the second generation of a device designed to improve polyp detection. The aim of this study was to evaluate its impact on adenoma detection rate (ADR) in routine colonoscopy. DESIGN: This cluster-randomised crossover trial compared Endocuff-assisted (ECV+) with standard (ECV-) colonoscopy. Two teams of 11 endoscopists each with prior ECV experience, balanced in terms of basal ADR, gender and case volume were compared. In randomised fashion, the teams started with ECV+ or ECV- and switched group after inclusion of half of the cases. The main outcome criterion was ADR difference between ECV+ and ECV-. Subgroup analysis was done for physicians with low and high ADR (< or ≥ 25%). RESULTS: During two periods of 20 and 21 weeks, respectively, the 22 endoscopists included 2058 patients (1032 ECV- vs 1026 ECV+, both groups being comparable). Overall ADR for both groups taken together was higher with ECV (39.2%) than without (29.4%; p<0.001) irrespective of the sequence of use (ECV+ or ECV- first), but mostly in adenomas <1 cm. In the physician subgroup analysis, only high detectors showed a significant ADR increase (from 31% to 41%, p<0.001), while the increase in the low detectors was not significant (from 24% to 30%, p=0.11). ECV had a positive impact in all colonic locations, except for the rectum. No ECV- related complication was reported. CONCLUSION: We observed a significant ADR difference of approximately 10% by the use of ECV. By subgroup analysis, this increase was significant only in physicians classified as high detectors. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03344055).

Difference in Physician- and Patient-Dependent Factors Contributing to Adenoma Detection Rate and Serrated Polyp Detection Rate.

BACKGROUND: Adenoma detection rate (ADR) is correlated with the risk of interval colorectal cancer and is considered as a quality benchmark for colonoscopy. Serrated polyp detection rate (SPDR) might be a more stringent indicator of quality in polyp detection. AIMS: To evaluate in a 2-year monocentric observational study patient-dependent and endoscopist-dependent factors influencing ADR and SPDR in daily practice. METHODS: We determined ADR and SPDR. We collected patient-dependent factors and endoscopist-dependent factors. Links between these data and detection rates were assessed by uni- and multivariate analysis. RESULTS: A total of 11682 colonoscopies were performed (female: 54.3%; male: 45.7%; median age 58) by 30 endoscopists (female: 9; male: 21). ADR and SPDR were 29.2% and 8%, respectively. In multivariate analysis, ADR was associated with patient-dependent factors: age (OR 1.044, CI 95% 1.040-1.048), male gender (OR 1.7, CI 95% 1.56-1.85), personal history of polyp/cancer (OR 1.53, CI 95% 1.3-1.9), and positive fecal immunochemical test (OR 2.47, CI 95% 2.0-3.1). In multivariate analysis, SPDR was associated with withdrawal time (OR 1.25, CI 95% 1.17-1.32), low volume activity (OR 1.3, CI 95% 1.1-1.52), and personal history of polyp/cancer (OR 1.61, CI 95% 1.15-2.25). CONCLUSION: In this large series of routine colonoscopies, we found that ADR was mainly driven by patient-dependent conditions, i.e., age, male gender, colonoscopy indication for positive FIT, and a personal history of polyp or cancer. In contrast, SPDR was mainly related to endoscopist-dependent factor, i.e., withdrawal time and low volume activity.

Adenoma and advanced neoplasia detection rates increase from 45 years of age.

BACKGROUND: Colonoscopy is considered a valid primary screening tool for colorectal cancer (CRC). The decreasing risk of CRC observed in patients undergoing colonoscopy is correlated with the adenoma detection rate (ADR). Due to the fact that screening programs usually start from the age of 50, very few data are available on the risk of adenoma between 40 and 49 years. However, the incidence of CRC is increasing in young populations and it is not uncommon in routine practice to detect adenomas or even advanced neoplasia during colonoscopy in patients under 50 years. AIM: To compare the ADR and advanced neoplasia detection rate (ANDR) according to age in a large series of patients during routine colonoscopy. METHODS: All consecutive patients who were scheduled for colonoscopy were included. Exclusion criteria were as follows: patients scheduled for partial colonoscopy or interventional colonoscopy (for stent insertion or stenosis dilation). Colonoscopies were performed in our unit by a team of 30 gastroenterologists in 2016. We determined the ADR and ANDR in each age group in the whole population and in the population with an average risk of CRC (excluding patients with personal or family history of advanced adenoma or cancer). RESULTS: 6027 colonoscopies were performed in patients with a median age of 57 years (range, 15-96). The ADR and ANDR were 28.6% and 9.7%, respectively, in the whole population. When comparing patients aged 40-44 (n = 382) and 45-49 years (n = 515), a strong increase in all parameters from 45 years was observed, with the ADR rising from 9.7% in patients aged 40-44 to 21.2% between 45 and 49 (P < 0.001) and the ANDR increasing from 3.1% in patients aged 40-44 to 6.4% in those aged 45-49 years (P < 0.03). With regard to patients aged 50-54 (n = 849), a statistically significant increase in the ADR and ANDR was not observed between patients aged 45-49 and those aged 50-54 years. In the population with an average risk of CRC, the ADR and ANDR were still significantly higher in patients aged 45-49 compared with those aged 40-44 years. CONCLUSION: This study shows a significant two-fold increase in the ADR and ANDR in patients aged 45 years and over.

Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer: A systematic review and pooled analysis.

The last two decades have seen intensive efforts devoted to the development of compounds that target angiogenesis for the treatment of metastatic colorectal cancer (mCRC). In this review, we describe supporting evidence and ongoing development of angiogenesis inhibitors in the second-line treatment of mCRC, and summarize relevant randomized trials to help therapeutic decision-making in daily practice.

[Gastric adenoma of pyloric type associated with familial adenomatous polyposis: A rare histological type not to be overlooked]. / Adénome gastrique de type pylorique au cours de la polypose adénomateuse familiale : une entité rare à ne pas méconnaître.

We report here two cases of gastric adenomas of pyloric type diagnosed during the follow-up of familial adenomatous polyposis (FAP). This rare histological lesion has been only recently described in this particular context and its clinical and pathological spectrum remains to be evaluated. Our two cases were very different in their clinical and endoscopic presentation. In the first patient, the lesion was diagnosed late during the evolution of FAP; it was very large and protruded above the adjacent mucosa; because of its large size, its treatment proved to be difficult. In the second patient, the lesion was discovered incidentally in gastric biopsies, early in the course of FAP. Both lesions presented the characteristic morphological and immunohistochemical features of pyloric adenoma, including the expression of MUC6. Both showed evidence of dysplasia, including high-grade dysplasia in the largest lesion. Pyloric adenoma belongs to the spectrum of gastric polyps associated with FAP; its prognosis and evolution remain to be evaluated.

Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study.

BACKGROUND: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. METHODS: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. RESULTS: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. CONCLUSION: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program.

BACKGROUND: Randomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting. METHODS: REBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models. RESULTS: Of 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12-month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis. CONCLUSION: The safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib. TRIAL REGISTRATION: Clinicaltrials.gov NCT02310477 .

Randomized controlled trial comparing outcomes of video capsule endoscopy with push enteroscopy in obscure gastrointestinal bleeding.

BACKGROUND: Optimal management of obscure gastrointestinal bleeding (OGIB) remains unclear. OBJECTIVE: To evaluate diagnostic yields and downstream clinical outcomes comparing video capsule endoscopy (VCE) with push enteroscopy (PE). METHODS: Patients with OGIB and negative esophagogastroduodenoscopies and colonoscopies were randomly assigned to VCE or PE and followed for 12 months. End points included diagnostic yield, acute or chronic bleeding, health resource utilization and crossovers. RESULTS: Data from 79 patients were analyzed (VCE n=40; PE n=39; 82.3% overt OGIB). VCE had greater diagnostic yield (72.5% versus 48.7%; P<0.05), especially in the distal small bowel (58% versus 13%; P<0.01). More VCE-identified lesions were rated possible or certain causes of bleeding (79.3% versus 35.0%; P<0.05). During follow-up, there were no differences in the rates of ongoing bleeding (acute [40.0% versus 38.5%; P not significant], chronic [32.5% versus 45.6%; P not significant]), nor in health resource utilization. Fewer VCE-first patients crossed over due to ongoing bleeding (22.5% versus 48.7%; P<0.05). CONCLUSIONS: A VCE-first approach had a significant diagnostic advantage over PE-first in patients with OGIB, especially with regard to detecting small bowel lesions, affecting clinical certainty and subsequent further small bowel investigations, with no subsequent differences in bleeding or resource utilization outcomes in follow-up. These findings question the clinical relevance of many of the discovered endoscopic lesions or the ability to treat most of these effectively over time. Improved prognostication of both patient characteristics and endoscopic lesion appearance with regard to bleeding behaviour, coupled with the impact of therapeutic deep enteroscopy, is now required using adapted, high-quality study methodologies.

Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer.

BACKGROUND: Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment. METHODS: This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/2/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate. RESULTS: Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days). CONCLUSION: Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.

Prognostic factors in node-negative colorectal cancer: a retrospective study from a prospective database.

PURPOSE: There is a need to identify a subgroup of high-risk patients with node-negative colorectal cancer who have a poor long-term prognosis and may benefit from adjuvant therapies. The aim of this study was to evaluate the prognostic impact of clinical and pathological parameters in a retrospective study from a prospective, continuous database of homogenously treated patients. METHODS: This study included 362 patients operated in a single institution for Dukes A and B (node-negative) colorectal cancer. The median follow-up was 140 months. The prognostic value of 13 clinical and pathological parameters was investigated. RESULTS: Multivariate analysis identified six independent prognostic factors: age at time of diagnosis (hazard ratio (HR) = 1.076), number of lymph nodes removed (HR = 0.948), perineural invasion (HR = 2.173), venous invasion (HR = 1.959), lymphatic vessel invasion (HR = 2.126), and T4 stage (HR = 5.876). CONCLUSION: These parameters could be useful in identifying patients with high-risk node-negative colorectal cancer who should be presented to adjuvant therapy.