Alex Kartheuser

Restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis revisited

Since restorative proctocolectomy (RPC) with ileal-pouch anal anastomosis (IPAA) removes the entire diseased mucosa, it has become firmly established as the standard operative procedure of choice for familial adenomatous polyposis (FAP). Many technical controversies still persist, such as mesenteric lengthening techniques, close rectal wall proctectomy, endoanal mucosectomy vs. double stapled anastomosis, loop ileostomy omission and a laparoscopic approach. Despite the complexity of the operation, IPAA is safe (mortality: 0.5–1%), it carries an acceptable risk of non-life-threatening complications (10–25%), and it achieves good long-term functional outcome with excellent patient satisfaction (over 95%). In contrast to the high incidence in patients operated for ulcerative colitis (UC) (15–20%), the occurrence of pouchitis after IPAA seems to be rare in FAP patients (0–11%). Even after IPAA, FAP patients are still at risk of developing adenomas (and occasional adenocarcinomas), either in the anal canal (10–31%) or in the ileal pouch itself (8–62%), thus requiring lifelong endoscopic monitoring. IPAA operation does not jeopardise pregnancy and childbirth, but it does impair female fecundity and has a low risk of impairment of erection and ejaculation in young males. The latter can almost completely be avoided by a careful “close rectal wall” proctectomy technique. Some argue that low risk patients (e.g. <5 rectal polyps) can be identified where ileorectal anastomosis (IRA) might be reasonable. We feel that the risk of rectal cancer after IRA means that IPAA should be recommended for the vast majority of FAP patients. We accept that in some very selected cases, based on clinical and genetics data (and perhaps influenced by patient choice regarding female fecundity), a stepwise surgical strategy with a primary IPA followed at a later age by a secondary proctectomy with IPAA could be proposed.

Use of the Circular Stapler in 1000 Consecutive Colorectal Anastomoses - Experience of One Surgical-team

BACKGROUNDnThis study was performed to assess the exact performance of the conventional way of stapling colorectal anastomoses. Information collected from 1000 consecutive anastomoses performed by one surgical team could be considered as reliable reference with which results obtained by new approaches could be compared.nnnMETHODSnOne thousand consecutive anastomoses were performed from 1979 to 1992. Characteristics of the procedure, intraoperative events, mortality rate, complications, and clinical outcome were detailed.nnnRESULTSnThere were 528 men and 472 women (age range, 20 to 90 years; average age, 63 years). Anastomoses were constructed by means of a circular stapler loaded with the largest cartridge in 82.3% of the cases. Imperfections were identified during operation in 124 cases. A diverting colostomy was performed in 127 cases. Postoperative mortality rate averaged 2.2%. Clinical anastomotic leaks developed in 35 patients: in 11.4% after low stapling (less than 5 cm from the dentate line) and in 2.2% after high stapling. The presence of a diverting colostomy influenced the leakage rate in patients with very low anastomoses. Total failure rate (death, definitive colostomy) as a result of anastomotic leak was 1.6%. Among the 933 survivors who had follow-up examination, the incidence of bad functional results decreased from 10% at the first attendance to 4.3% at the last one. Transanal dilatation and restapling were required for symptomatic narrowing in three and one patients, respectively.nnnCONCLUSIONSnThe conventional way of stapling colorectal anastomoses in reliable, but it requires strict observance of the rules for anastomosing intestine and a careful check of the stapled sutures. Results obtained by new approaches could be compared with these data.

Epiploic appendagitis: color Doppler sonographic findings.

Abstract The aim of this study was to analyze the color Doppler sonographic findings in primary epiploic appendagitis. Color Doppler sonographic findings of ten patients with primary epiploic appendagitis were reviewed. The following sonographic features were analyzed: identification of a mass adjacent to the colonic wall; identification of spotty color areas with arterial flow in this mass and detection of abnormalities of the colonic wall adjacent to the infiltrated fatty tissue. A well-delineated hyperechoic mass adjacent to the colonic wall was detected in each patient with sonography. No colonic wall abnormalities were observed nor color Doppler signal in and around the hyperechoic area. Absence of flow at color Doppler sonography is an additional feature of epiploic appendagitis.

Novel germline mutations in the APC gene and their phenotypic spectrum in familial adenomatous polyposis kindreds.

Abstract Among 23 germline mutations identified in the APC screening of 45 familial adenomatous polyposis (FAP) patients, we have found 10 different novel frameshift mutations in 11 apparently unrelated patients. In two cases, an additional missense mutation was detected. One previously described as a causative germline mutation (S2621C), associated with a 1-bp insertion (4684insA) on the opposite allele, did not segregate with the FAP phenotype in the family and was therefore considered as being non-pathogenic. The other (Z1625H) was located 2 codons before a 1-bp deletion (4897delC). Both mutations were transmitted together from an FAP father to his affected son. The FAP phenotype of these 10 novel truncating mutations was clinically documented within their kindreds. Important variability was observed in the phenotype. Interestingly, we noted that a mutation (487insT) localized at the boundary of the 5’ attenuated APC phenotype region in two unrelated families resulted in classical polyposis. A clear-cut genotype-phenotype correlation could be drawn in only two instances. In one family, a 4684insA mutation led to a mild polyposis associated with early inherited osteomas and, in the family bearing the double mutation (Z1625H+4897delC), the phenotype was obviously a 3′ attenuated type. Our data illustrate the wide genetic and phenotypic heterogeneity of this condition between and within the families, making the establishment of correlations complex and any prediction in this disease difficult, although targeting the mutation site may be helpful in some specific cases.

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

BACKGROUNDnThe 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.nnnMETHODSnAn 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.nnnFINDINGSnTissue 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.nnnINTERPRETATIONnThe 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.nnnFUNDINGnFrench 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.

Insights into fast-track colon surgery: a plea for a tailored program

BackgroundThis retrospective study compared the fast-track colon surgery program to conventional perioperative care and assessed factors that influence postoperative length of stay.DesignThis retrospective study included 124 fast-track and 119 conventional care colon surgical patients. Exclusion criteria were primary rectal disease, stoma, American Society of Anesthesiologists score IV, and Association Française de Chirurgie index 3 or 4. Laparoscopy was the preferred approach. Variables influencing length of stay were analyzed by multivariate linear and logistic regression.ResultsOverall mortality and complication rates were not significantly different between groups (fast-track vs. controls 0 vs. 0.8xa0%, 30.6 vs. 38.6xa0% respectively). As expected, median length of stay was significantly reduced in fast-track patients (3 vs. 6xa0days, pxa0<xa00.001), but emergency readmission rate was higher (16.9 vs. 7.6xa0%, pxa0=xa00.026), although rehospitalization rates were similar (8 vs. 4.2xa0%, not significant). Independent risk factors of increased length of stay were identified as age >69xa0years (pxa0=xa00.001), laparotomy (pxa0=xa00.011), and conventional perioperative care (pxa0<xa00.001).ConclusionsThe introduction of a fast-track program reduced postoperative length of stay without increasing complication rate. This study proposes a modulation of the program according to patient age and surgical approach.

Perforation sigmoïdienne traumatique : intérêt du bilan tomodensitométrique

The authors report a case of a delayed traumatic perforation of the sigmoid colon, presenting three days after a motor vehicle accident. A review of the literature is presented.The authors report a case of a delayed traumatic perforation of the sigmoid colon, presenting three days after a motor vehicle accident. A review of the literature is presented.

Evolution of Metastases in Space and Time under Immune Selection

We examined how the immune microenvironment molds tumor evolution at different metastatic organs in a longitudinal dataset of colorectal cancer. Through multiplexed analyses, we showed that clonal evolution patterns during metastatic progression depend on the immune contexture at the metastatic site. Genetic evidence of neoantigen depletion was observed in the sites with high Immunoscore and spatial proximity between Ki67+ tumor cells and CD3+ cells. The immunoedited tumor clones were eliminated and did not recur, while progressing clones were immune privileged, despite the presence of tumor-infiltrating lymphocytes. Characterization of immune-privileged metastases revealed tumor-intrinsic and tumor-extrinsic mechanisms of escape. The lowest recurrence risk was associated with high Immunoscore, occurrence of immunoediting, and low tumor burden. We propose a parallel selection model of metastatic progression, where branched evolution could be traced back to immune-escaping clones. The findings could inform the understanding of cancer dissemination and the development of immunotherapeutics.

Effet du volume hospitalier sur la qualité des soins et les résultats oncologiques après chirurgie pour cancer du rectum

Introduction Les etudes analysant le rapport entre qualite des soins et volume hospitalier en matiere de cancer du rectum sont peu nombreuses. Pourtant, la centralisation vers des centres experts semble encouragee. But Evaluer l’effet du volume hospitalier sur la qualite des soins multi-disciplinaires du cancer rectal. Methodes De 2006 a 2011, 1 469 patients presentant un cancer du moyen ou bas rectum ont beneficie d’une proctectomie avec exerese totale du mesorectum et ont ete prospectivement inclus dans PROCARE, projet Belge d’ameliorations des soins. Le volume de patients a ete derive d’une base de donnees nationale et analyse comme variable continue. Les soins sont evalues par des indicateurs de qualite soit individuels soit groupes par domaine. Resultats Un effet du volume est observe sur le taux d’administration d’un traitement neoadjuvant pour les stades II-III. revaluation pre-operatoire de la marge de resection circonferentielle, le taux de resection complete, le taux de resection abdomino-perineale et le nombre de ganglions lymphatiques examines apres radiochimiotherapie. La chirurgie est le seul domaine pour lequel la qualite est correlee au volume. Par contre, aucun effet volume n’est observe sur les resultats oncologiques. Conclusion Un effet du volume sur la qualite des soins du cancer rectal est observe mais se limite a un petit nombre d’indicateurs. Il n’y a pas d’effet sur les resultats oncologiques.