Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial.

BACKGROUND: Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. METHODS/DESIGN: Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. DISCUSSION: Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345669.

PGE2-induced colon cancer growth is mediated by mTORC1

La mortalité du cancer colorectal reste importante malgré les nombreux progrès effectués dans la compréhension des mécanismes responsables à son développement. Dans ce contexte, il a été démontré qu'une enzyme appelée cyclooxygénase-2 (COX-2) joue un rôle important dans la pathogenèse du cancer colorectal. En effet, les métabolites produits par cette enzyme, en particulier la Prostaglandine E2 (PGE2), sont capables de directement stimuler la prolifération et la survie des cellules tumorales nécessaires à la progression tumorale. De plus, la PGE2 stimule également la formation de nouveaux vaisseaux sanguins indispensable à la croissance tumorale en induisant la formation du facteur de croissance vasculaire (VEGF). L'importance de COX- 2 dans le cancer colorectal ne se limite pas au niveau expérimental mais a aussi été démontré chez des patients où il a été prouvé que des inhibiteurs chimiques de COX-2 comme l'aspirine réduisaient le risque de développer un cancer colorectal. Il est donc important de caractériser et de comprendre les mécanismes par lesquels la COX-2 et les PGE2 participent au développement du cancer colorectal afin de générer de nouvelles approches thérapeutiques. Dans cette étude, nous avons observé qu'un complexe protéique intracellulaire appelé mTORC1 joue un rôle important dans la prolifération de cellules du cancer colorectal induite par la PGE2. En effet, nous avons trouvé que l'activité de mTORC1 était augmentée après stimulation des cellules tumorales par la PGE2. Nous avons également trouvé que cette stimulation était médiée par un type spécifique de récepteurs de la PGE2 appelé EP4. L'inhibition de mTORC1 par des composés chimiques ou par interférence de RNA bloque la prolifération cellulaire induite par la PGE2. De même, la production du facteur de croissance endothéliale (VEGF) par la PGE2 est bloquée par les inhibiteurs de mTORC1. Nos résultats montrent donc que mTORC1 est un intermédiaire cellulaire important dans la croissance tumorale induite par la PGE2 ainsi que dans la production de VEGF. mTORC1 représente de ce fait une cible thérapeutique intéressante dans le cancer colorectal qui mérite d'être évaluée dans des études cliniques.

18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.

Long-term follow-up of colorectal carcinoma patients by repeated CEA radioimmunoassay.

One of the major practical applications of carcinoembryonic antigen (CEA) assay is the monitoring of colorectal carcinoma patients after complete tumor resection. During the last 5 years, we have followed by repeated CEA assays 66 patients with histologically confirmed colon or rectum adenocarcinoma. Among 19 patients who developed a tumor recurrence, 17 had increased CEA levels preceding the clinical diagnosis by 2 to 26 months. Among the 47 patients who did not show any clinical evidence of tumor recurrence, 35 had CEA values remaining below the limit of 5 ng/ml, whereas 12 had moderate elevations of CEA level fluctuating around this limit. The majority of patients in this last group were heavy smokers or had liver enlargement, but in a few of them we did not find a satisfactory explanation for their moderately increased CEA levels. While our results confirm that repeated CEA assays can predict tumor recurrence with a lead time of several months over clinical diagnosis, they also give a word of warning concerning the interpretation of moderate elevations of CEA level. A moderate increase of CEA level can be the result of early distant metastases, local recurrence or exacerbation of an inflammatory disease. We feel that the decision of second look operations based on CEA results should be made only if increasing CEA values have been observed on three different blood samples taken within a period of 3 months and if no nonmalignant diseases known to increase CEA level are present. Ultimately only randomized clinical studies will determine if second look operations motivated by elevated CEA levels can improve the quality and length of survival of patients with colorectal carcinoma.

Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study.

PURPOSE: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL.¦PATIENTS AND METHODS: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242).¦RESULTS: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score ≤1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC.¦CONCLUSION: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

European cancer mortality predictions for the year 2012.

BACKGROUND: Estimating current cancer mortality figures is important for defining priorities for prevention and treatment.Materials and methods:Using logarithmic Poisson count data joinpoint models on mortality and population data from the World Health Organization database, we estimated numbers of deaths and age-standardized rates in 2012 from all cancers and selected cancer sites for the whole European Union (EU) and its six more populated countries. RESULTS: Cancer deaths in the EU in 2012 are estimated to be 1 283 101 (717 398 men and 565 703 women) corresponding to standardized overall cancer death rates of 139/100 000 men and 85/100 000 women. The fall from 2007 was 10% in men and 7% in women. In men, declines are predicted for stomach (-20%), leukemias (-11%), lung and prostate (-10%) and colorectal (-7%) cancers, and for stomach (-23%), leukemias (-12%), uterus and colorectum (-11%) and breast (-9%) in women. Almost stable rates are expected for pancreatic cancer (+2-3%) and increases for female lung cancer (+7%). Younger women show the greatest falls in breast cancer mortality rates in the EU (-17%), and declines are expected in all individual countries, except Poland. CONCLUSION: Apart for lung cancer in women and pancreatic cancer, continuing falls are expected in mortality from major cancers in the EU.

Impact of lung function changes after induction radiochemotherapy on resected T4 non-small cell lung cancer outcome.

BACKGROUND: Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. METHODS: A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. RESULTS: The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. CONCLUSIONS: In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.

Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.

Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE(2)-induced intestinal carcinogenesis are unclear. Here we report that PGE(2) indirectly transactivates PPARdelta through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE(2) treatment of Apc(min) mice dramatically increased intestinal adenoma burden, which was negated in Apc(min) mice lacking PPARdelta. We demonstrate that PPARdelta is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.

Impact of induction therapy on airway complications after sleeve lobectomy for lung cancer.

BACKGROUND: Sleeve lobectomy is a valid alternative to pneumonectomy for the treatment of centrally located operable non-small cell lung cancer (NSCLC), but concern has been evoked regarding a potentially increased risk of bronchial anastomosis complications after induction therapy. This study examined the impact of induction therapy on airway healing after sleeve lobectomy for NSCLC. METHODS: Bronchial anastomosis complications were recorded with respect to the induction regimen applied (neoadjuvant chemotherapy vs chemoradiotherapy) in a consecutive series of patients with sleeve lobectomy for NSCLC. RESULTS: Ninety-nine patients underwent sleeve resection, 28 of them after induction therapy. Twelve patients received chemotherapy alone, and 16 patients had radiochemotherapy. There were no significant differences in postoperative 90-day mortality (3.6% vs 2.8%) and morbidity (54% vs 49%) for patients with and without induction therapy. Bronchial anastomosis complications occurred in 3 patients (10.8%) with neoadjuvant therapy and in 2 (2.8%) without (p = 0.3). In the induction therapy group, two bronchial stenoses occurred after radiochemotherapy and one bronchopleural fistula after chemotherapy alone. In patients without induction therapy, one bronchial stenosis and one bronchopleural fistula were observed. All bronchial stenoses were successfully treated by dilatation, and both bronchopleural fistulas occurring after right lower lobectomy were successfully treated by reoperation and completion sleeve bilobectomy with preservation of the upper lobe. CONCLUSIONS: Sleeve lobectomy for NSCLC can be safely performed after induction chemotherapy and radiochemotherapy with mortality and incidence of airway complications similar to that observed in nonpretreated patients. The treatment of airway complications does not differ for patients with and without induction therapy.

Development of a Liver-specific Tet-On Inducible System for AAV Vectors and Its Application in the Treatment of Liver Cancer.

Recombinant adeno-associated virus (rAAV) are effective gene delivery vehicles that can mediate long-lasting transgene expression. However, tight regulation and tissue-specific transgene expression is required for certain therapeutic applications. For regulatable expression from the liver we designed a hepatospecific bidirectional and autoregulatory tetracycline (Tet)-On system (Tet(bidir)Alb) flanked by AAV inverted terminal repeats (ITRs). We characterized the inducible hepatospecific system in comparison with an inducible ubiquitous expression system (Tet(bidir)CMV) using luciferase (luc). Although the ubiquitous system led to luc expression throughout the mouse, luc expression derived from the hepatospecific system was restricted to the liver. Interestingly, the induction rate of the Tet(bidir)Alb was significantly higher than that of Tet(bidir)CMV, whereas leakage of Tet(bidir)Alb was significantly lower. To evaluate the therapeutic potential of this vector, an AAV-Tet(bidir)-Alb-expressing interleukin-12 (IL-12) was tested in a murine model for hepatic colorectal metastasis. The vector induced dose-dependent levels of IL-12 and interferon-γ (IFN-γ), showing no significant toxicity. AAV-Tet(bidir)-Alb-IL-12 was highly efficient in preventing establishment of metastasis in the liver and induced an efficient T-cell memory response to tumor cells. Thus, we have demonstrated persistent, and inducible in vivo expression of a gene from a liver-specific Tet-On inducible construct delivered via an AAV vector and proved to be an efficient tool for treating liver cancer.

Targeting the JNK signaling pathway potentiates the antiproliferative efficacy of Rapamycin in LS174T colon cancer cells

RésuméLes récentes thérapies anticancéreuses développées visent principalement à inhiber les protéines mutées et responsables de la croissance des cellules cancéreuses. Dans ce contexte, l'inhibition d'une protéine appelée mTOR est une stratégie prometteuse. En effet, mTOR régule la prolifération et la survie cellulaire et mTOR est fréquemment activé dans les cellules tumorales.De nombreuses études ont démontré l'efficacité anti-tumorale d'inhibiteurs de mTOR telle que la rapamycine aussi bien dans des modèles expérimentaux que chez les patients souffrant de cancers. Ces études ont cependant également démontré que l'inhibition de mTOR induit l'activation d'autres protéines cellulaires qui vont induire la prolifération cellulaire et ainsi limiter l'effet anti-tumoral des inhibiteurs de mTOR. En particulier, la rapamycine induit l'activation de la voie de signalisation PI3K/Akt qui joue un rôle prépondérant dans la croissance cellulaire.Dans ce travail, nous avons étudié l'effet de la rapamycine sur une protéine appelée JNK ainsi que le rôle de JNK sur les effets anti-tumoraux de la rapamycine. JNK est une protéine impliquée dans la survie et la prolifération cellulaire. Elle est activée notamment par la voie de signalisation PI3K/Akt. De ce fait, nous avons émis l'hypothèse que la rapamycine induirait l'activation de JNK, réduisant ainsi l'efficacité anti¬tumorale de la rapamycine. En utilisant une lignée cellulaire tumorale (LS174T) dérivée du cancer colorectal, nous avons observé que la rapamycine induisait l'activation de JNK. Nous avons également observé que l'inhibition de JNK par le SP600125, un inhibiteur chimique de JNK, ou par la surexpression d'un dominant négatif de JNK dans les cellules LS174T potentialisait l'effet anti-tumoral de la rapamycine in vitro ainsi que dans un modèle murin de xénogreffe tumorale in vivo.En conclusion, nous avons observé que l'activation de JNK induite par la rapamycine entraine une réduction de l'effet anti-tumoral de cette dernière. Nous proposons ainsi que l'inhibition simultanée de JNK et de mTOR représente une nouvelle option thérapeutique en oncologie qu'il conviendra de confirmer dans d'autres modèles expérimentaux avant d'être testée dans des études cliniques.

History of cholelithiasis and cancer risk in a network of case-control studies.

Background We analyzed the relationship between cholelithiasis and cancer risk in a network of case-control studies conducted in Italy and Switzerland in 1982-2009. Methods The analyses included 1997 oropharyngeal, 917 esophageal, 999 gastric, 23 small intestinal, 3726 colorectal, 684 liver, 688 pancreatic, 1240 laryngeal, 6447 breast, 1458 endometrial, 2002 ovarian, 1582 prostate, 1125 renal cell, 741 bladder cancers, and 21 284 controls. The odds ratios (ORs) were estimated by multiple logistic regression models. Results The ORs for subjects with history of cholelithiasis compared with those without were significantly elevated for small intestinal (OR = 3.96), prostate (OR = 1.36), and kidney cancers (OR = 1.57). These positive associations were observed ≥10 years after diagnosis of cholelithiasis and were consistent across strata of age, sex, and body mass index. No relation was found with the other selected cancers. A meta-analysis including this and three other studies on the relation of cholelithiasis with small intestinal cancer gave a pooled relative risk of 2.35 [95% confidence interval (CI) 1.82-3.03]. Conclusion In subjects with cholelithiasis, we showed an appreciably increased risk of small intestinal cancer and suggested a moderate increased risk of prostate and kidney cancers. We found no material association with the other cancers considered.

European cancer mortality predictions for the year 2015 : does lung cancer have the highest death rate in EU women?

BACKGROUND: Cancer mortality statistics for 2015 were projected from the most recent available data for the European Union (EU) and its six more populous countries. Prostate cancer was analysed in detail. PATIENTS AND METHODS: Population and death certification data from stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukaemias and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected 2015 numbers of deaths by age group were obtained by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: A total of 1 359 100 cancer deaths are predicted in the EU in 2015 (766 200 men and 592 900 women), corresponding to standardised death rates of 138.4/100 000 men and 83.9/100 000 women, falling 7.5% and 6%, respectively, since 2009. In men, predicted rates for the three major cancers (lung, colorectum and prostate) are lower than in 2009, falling 9%, 5% and 12%. Prostate cancer showed predicted falls of 14%, 17% and 9% in the 35-64, 65-74 and 75+ age groups. In women, breast and colorectal cancers had favourable trends (-10% and -8%), but predicted lung cancer rates rise 9% to 14.24/100 000 becoming the cancer with the highest rate, reaching and possibly overtaking breast cancer rates-though the total number of deaths remain higher for breast (90 800) than lung (87 500). Pancreatic cancer has a negative outlook in both sexes, rising 4% in men and 5% in women between 2009 and 2015. CONCLUSIONS: Cancer mortality predictions for 2015 confirm the overall favourable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 21% in women, and the avoidance of over 325 000 deaths in 2015 compared with the peak rate.

Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial.

BACKGROUND: One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. METHODS: We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. FINDINGS: From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. INTERPRETATION: Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi.

Rectal enema is an alternative to full mechanical bowel preparation for primary rectal cancer surgery.

AIM: According to the French GRECCAR III randomized trial, full mechanical bowel preparation (MBP) for rectal surgery decreases the rate of postoperative morbidity, in particular postoperative infectious complications, but MBP is not well tolerated by the patient. The aim of the present study was to determine whether a preoperative rectal enema (RE) might be an alternative to MBP. METHODS: An analysis was performed of 96 matched cohort patients undergoing rectal resection with primary anastomosis and protective ileostomy at two different university teaching hospitals, whose rectal cancer management was comparable except for the choice of preoperative bowel preparation (MBP or RE). Prospective databases were retrospectively analysed. RESULTS: Patients were well matched for age, gender, body mass index and Charlson index. The surgical approach and cancer characteristics (level above anal verge, stage and use of neoadjuvant therapy) were comparable between the two groups. Anastomotic leakage occurred in 10% of patients having MBP and in 8% having RE (P = 1.00). Pelvic abscess formation (6% vs 2%, P = 0.63) and wound infection (8% vs 15%, P = 0.55) were also comparable. Extra-abdominal infection (13% vs 13%, P = 1.00) and non-infectious abdominal complications such as ileus and bleeding (27% and 31%, P = 0.83) were not significantly different. Overall morbidity was comparable in the two groups (50% vs 54%, P = 0.83). CONCLUSION: A simple RE before rectal surgery seems not to be associated with more postoperative infectious complications nor a higher overall morbidity than MBP.