Daniel Léonard

Neoplasms of Anal Canal and Perianal Skin

Tumors of the anus and perianal skin are rare. Their presentation can vary and often mimics common benign anal pathology, thereby delaying diagnosis and appropriate and timely treatment. The anatomy of this region is complex because it represents the progressive transition from the digestive system to the skin with many different co-existing types of cells and tissues. Squamous cell carcinoma of the anal canal is the most frequent tumor found in the anal and perianal region. Less-frequent lesions include Bowens and Pagets disease, basal cell carcinoma, melanoma, and adenocarcinoma. This article aims to review the clinical presentation, diagnostic evaluation, and treatment options for neoplasms of the anal canal and perianal skin.

Waist Circumference and Waist/Hip Ratio Are Better Predictive Risk Factors for Mortality and Morbidity after Colorectal Surgery Than Body Mass Index and Body Surface Area

Objectives:To determine whether body fat distribution, measured by waist circumference (WC) and waist/hip ratio (WHR), is a better predictor of mortality and morbidity after colorectal surgery than body mass index (BMI) or body surface area (BSA). Background:Obesity measured by BMI is not a consistent risk factor for postoperative mortality and morbidity after abdominal surgery. Studies in metabolic and cardiovascular diseases have shown WC and WHR to be better outcome predictors than BMI. Methods:A prospective multicenter international study was conducted among patients undergoing elective colorectal surgery. The WHR, BMI, and BSA were derived from body weight, height, and waist and hip circumferences measured preoperatively. Uni- and multivariate analyses were performed to identify risk factors for postoperative outcomes. Results:A total of 1349 patients (754 men) from 38 centers in 11 countries were included. Increasing WHR significantly increased the risk of conversion [odds ratio (OR) = 15.7, relative risk (RR) = 4.1], intraoperative complications (OR = 11.0, RR = 3.2), postoperative surgical complications (OR = 7.7, RR = 2.0), medical complications (OR = 13.2, RR = 2.5), anastomotic leak (OR = 13.7, RR = 3.3), reoperations (OR = 13.3, RR = 2.9), and death (OR = 653.1, RR = 21.8). Both BMI (OR = 39.5, RR = 1.1) and BSA (OR = 4.9, RR = 3.1) were associated with an increased risk of abdominal wound complication. In multivariate analysis, the WHR predicted intraoperative complications, conversion, medical complications, and reinterventions, whereas BMI was a risk factor only for abdominal wall complications; BSA did not reach significance for any outcome. Conclusions:The WHR is predictive of adverse events after elective colorectal surgery. It should be used in routine clinical practice and in future risk-estimating systems.

Factors predicting the quality of total mesorectal excision for rectal cancer.

Objective: To determine preoperative tumor-, patient-, and treatment-related factors that are independently associated with incomplete mesorectal excision. Summary of Background Data: Incomplete total mesorectal excision (TME) for rectal cancer is associated with increased local and overall recurrences. Factors predicting incomplete mesorectal excision have scarcely been studied. Methods: In the context of PROCARE, a Belgian multidisciplinary project on rectal cancer, the quality of 266 consecutive and anonymized TME specimens submitted by 33 candidate-TME-trainers was graded by a blinded pathology review board in a standardized manner. Uni- and multivariable analysis were performed to identify factors that can independently predict incomplete mesorectal excision. Results: Mesorectal resection was complete in 21%, nearly complete in 47%, and incomplete in 32%. Of 57% of TME specimens the grade of resection had not been reported by the local pathologist. Incomplete TME doubled the incidence of a positive circumferential resection margin (P = 0.004). Factors found to be significantly related to incomplete TME in univariate analysis were as follows: surgeon, female gender, pathologic body mass index, low rectal cancer, negative clinical nodal status, the absence of downstaging after long-course chemoradiation, laparoscopic and converted laparoscopic resection, and abdominoperineal resection. Multivariable analysis identified pathologic body mass index (P = 0.017), the absence of downstaging after long-course chemoradiation (P = 0.0005), and laparoscopic or converted laparoscopic resection (P = 0.014) as factors that are independently associated with incomplete mesorectal excision. Conclusion: Good TME quality cannot be guaranteed. This peer-reviewed TME assessment revealed a number of factors that are independently related to incomplete TME. Both specimen and pathology report need to be audited.

International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study

BACKGROUND The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer. METHODS An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrells C-statistics was used to assess model performance. FINDINGS Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0·97 for colon tumour; r=0·97 for invasive margin; p<0·0001). In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (14 [8%] patients with a high Immunoscore vs 65 (19%) patients with an intermediate Immunoscore vs 51 (32%) patients with a low Immunoscore; hazard ratio [HR] for high vs low Immunoscore 0·20, 95% CI 0·10-0·38; p<0·0001). The findings were confirmed in the two validation sets (n=1981). In the stratified Cox multivariable analysis, the Immunoscore association with time to recurrence was independent of patient age, sex, T stage, N stage, microsatellite instability, and existing prognostic factors (p<0·0001). Of 1434 patients with stage II cancer, the difference in risk of recurrence at 5 years was significant (HR for high vs low Immunoscore 0·33, 95% CI 0·21-0·52; p<0·0001), including in Cox multivariable analysis (p<0·0001). Immunoscore had the highest relative contribution to the risk of all clinical parameters, including the American Joint Committee on Cancer and Union for International Cancer Control TNM classification system. INTERPRETATION The Immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer. These results support the implementation of the consensus Immunoscore as a new component of a TNM-Immune classification of cancer. FUNDING French National Institute of Health and Medical Research, the LabEx Immuno-oncology, the Transcan ERAnet Immunoscore European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, Institut National du Cancer, Italian Association for Cancer Research, national grants and the Society for Immunotherapy of Cancer.

Effect of hospital volume on quality of care and outcome after rectal cancer surgery

Research on the relationship between hospital volume and quality of care in the treatment of rectal cancer is limited.

Multitechnique Study of Hexatriacontane Surfaces Modified By Argon and Oxygen Rf Plasmas - Effect of Treatment Time and Functionalization, and Comparison With Hdpe

Hexatriacontane (C36H74) has been used as a model molecule for the study of the surface modifications of high-density polyethylene (HDPE) in argon and oxygen radio-frequency (RF) plasmas. The combination of static secondary ion mass spectrometry (SIMS), ion scattering spectroscopy (ISS), X-ray photoelectron spectroscopy (XPS), and contact angle measurements has constituted a powerful method for the investigation of the surface modifications induced by the plasma treatments. The surface degradation and functionalization are shown to depend on both the nature of the treated material and the nature of the plasma atmosphere. The SSIMS results obtained on plasma-modified hexatriacontane and HDPE are compared in order to identify the nature of the functionalities present at the plasma-treated surfaces. Finally, plasma treatment 180 atmosphere was performed on HDPE, C36H74, and polystyrene (PS). In that case, the isotopic specificity of both ISS and SIMS allowed the determination of the relative concentrations of O-16 and O-18 in relation to the probed depth and plasma atmosphere.

Novel insight into the role of microbiota in colorectal surgery

Recent literature undeniably supports the idea that the microbiota has a strong influence on the healing process of an intestinal anastomosis. Understanding the mechanisms by which the bacterial community of the gut influences intestinal healing could open the door for new preventive and therapeutic approaches. Among the different mechanisms, data have shown that the production of specific reactive oxygen species (ROS) and the activation of specific formyl peptide receptors (FPRs) regulate intestinal wound healing. Evidence suggests that specific gut microbes such as Lactobacillus spp and Akkermansia muciniphila help to regulate healing processes through both ROS-dependent and FPR-dependent mechanisms. In this review, we will discuss the current knowledge and future perspectives concerning the impact of microbiota on wound healing. We will further review available evidence on whether mechanical bowel preparation and the use of specific antibiotics are beneficial or harmful procedures, an ongoing matter of debate. These practices have a profound effect on the gut microbiota composition at the level of both the mucosal and the luminal compartments. Therefore, a key question remains unanswered: should we continue to prepare the gut before surgical intervention? Current knowledge and data do not clearly support the use of one technique or another to avoid complications such as anastomotic leak. There is an urgent need for appropriate interventions with a deep microbiota analysis to investigate both the surgical technical benefits of a proper anastomosis compared with the potential effect of the gut microbes (beneficial vs harmful) on the processes of wound healing and anastomotic leakage reduction.

The Concept of Titration can be Transposed to Fluid Management. But does is Change the Volumes? Randomised Trial on Pleth Variability Index During Fast-Track Colonic Surgery

BACKGROUND The concept of drug titration emerged recently for intraoperative fluid administration during Fast-Track colonic surgery to avoid hypovolemia as well as excessive crystalloid administration. The Pleth Variability Index (PVI) is an oximeter-derived parameter. It allows a continuous monitoring of the respiratory variation of the perfusion index. OBJECTIVE To investigate if applying the concept of fluid titration with PVI-guided colloid administration conjointly with restricted crystalloids administration changes the amount of fluid administered. DESIGN, SETTINGS AND PATIENTS: Twenty one ASA 2 patients scheduled for Fast-Track colonic surgery were randomized in two groups: the PVI-guided the fluid management group and the the control group. INTERVENTION AND MAIN OUTCOME MEASURES After the induction of general anesthesia, the PVI group received a 10 mL.kg- 1.h-1 infusion of crystalloid during the first hour, reduced to 2 mL.kg-1.h-1 thereafter. Colloids 250 mL were administered if necessary to maintain a PVI value of 10 to 13%. In the control group, a 10 mL.kg-1.h-1 infusion of crystalloid during the first hour was followed by a 5 mL.kg-1.h-1 infusion. Boluses of 250 mL of colloids were administered if required to maintain the mean arterial pressure above 65 mmHg. RESULTS Intraoperative crystalloids infused volume were significantly lower in the PVI group (925+/-262 mL vs 1129+/- 160 mL; P=0.04). In contrast, the infused amounts of colloids was higher in the PVI group (725+/-521 mL vs 250+/-224 mL; P=0.01). Interestingly, total fluid amount infused intra- ant postoperatively were similar between the groups (1650+/- 807 mL vs 1379+/-186 mL; P=0.21). CONCLUSION PVI-guided fluid management in Fast-Track colonic surgery is not necessarily associated with different total volume infused.

The transanal endoscopic microsurgery procedure: standards and extended indications.

Transanal endoscopic microsurgery (TEM) was developed in the early 1980s as a minimally invasive technique allowing the resection of benign rectal adenomas. For this indication, TEM was reported to be safe and effective and even exceeded the results compared to classical local excision. Unsurprisingly, the indication expanded to small rectal cancer. There is still much debate, though, whether it is oncologically safe to perform TEM for rectal cancer. Much has been published about the need for proper patient selection, i.e. patients presenting a low-risk T1 rectal cancer seem to be the most adequate subgroup for this technique. Nevertheless, TEM remains controversial concerning high-risk T1 rectal adenocarcinomas and deeper infiltrating tumors. Several retrospective case series and a small prospective study suggest that radiochemotherapy before local excision reduces recurrence to a level comparable with classic radical surgery (total mesorectal excision). However, these studies are collectively limited, and prospective data from larger multicenter trials are awaited. Reports about functional results after TEM have shown that the procedure has no permanent impact on anorectal function. Even if transient anal resting pressure weakening has been repeatedly described, patients do not suffer from any long-term functional sequelae. Nor do they complain of quality of life impairment.

Quantitative Contribution of Prognosticators to Oncologic Outcome After Rectal Cancer Resection

BACKGROUND: Prognostication is an important aspect of medical practice. It relies on statistical modeling testing the correlation of variables with the outcome of interest. OBJECTIVE: In contrast with the classic approach of predictive modeling, this study aimed to estimate the unique, individual, and relative contributions. This includes the quantitative contributions of patient-, tumor-, and treatment-related factors to oncologic outcome after rectal cancer resection. DESIGN: This was a retrospective analysis of prospectively registered data. SETTINGS: The study included 65 hospitals participating on a voluntary basis in the Project on Cancer of the Rectum, a Belgian multidisciplinary improvement project of rectal cancer care. PATIENTS: A total of 1470 patients presenting midrectal or low-rectal adenocarcinoma without distant metastasis were included. INTERVENTION: The study intervention was total mesorectal excision with or without sphincter preservation. MAIN OUTCOME MEASURES: The unique, individual, and relative contributions of a set of covariables to the statistical variability of the distant metastasis rate and overall survival have been calculated. RESULTS: The 5-year distant metastasis rate was 21% and overall survival 76%. A large amount of the variability of the outcomes (ie, 83.6% to 84.2%) could not be predicted by the prognostic factors. Unique contributions of the predictors ranged from 0.1% to 3.1%. The 3 risk factors with the highest unique contribution for distant metastasis were lymph node ratio, pathologic tumor stage, and total mesorectal quality; for overall survival they were age, lymph node ratio, and ASA score. LIMITATIONS: The main weakness of this study was incomplete participation and registration in the Project on Cancer of the Rectum. CONCLUSIONS: Several factors influence oncologic outcomes and are present in prediction models. However, the models predict relatively little of outcome variation.