Cécile Brigand

Guidelines for management of intra-abdominal infections.

Intra-abdominal infections are one of the most common gastrointestinal emergencies and a leading cause of septic shock. A consensus conference on the management of community-acquired peritonitis was published in 2000. A new consensus as well as new guidelines for less common situations such as peritonitis in paediatrics and healthcare-associated infections had become necessary. The objectives of these Clinical Practice Guidelines (CPGs) were therefore to define the medical and surgical management of community-acquired intra-abdominal infections, define the specificities of intra-abdominal infections in children and describe the management of healthcare-associated infections. The literature review was divided into six main themes: diagnostic approach, infection source control, microbiological data, paediatric specificities, medical treatment of peritonitis, and management of complications. The GRADE(®) methodology was applied to determine the level of evidence and the strength of recommendations. After summarising the work of the experts and application of the GRADE(®) method, 62 recommendations were formally defined by the organisation committee. Recommendations were then submitted to and amended by a review committee. After 2 rounds of Delphi scoring and various amendments, a strong agreement was obtained for 44 (100%) recommendations. The CPGs for peritonitis are therefore based on a consensus between the various disciplines involved in the management of these patients concerning a number of themes such as: diagnostic strategy and the place of imaging; time to management; the place of microbiological specimens; targets of empirical anti-infective therapy; duration of anti-infective therapy. The CPGs also specified the value and the place of certain practices such as: the place of laparoscopy; the indications for image-guided percutaneous drainage; indications for the treatment of enterococci and fungi. The CPGs also confirmed the futility of certain practices such as: the use of diagnostic biomarkers; systematic relaparotomies; prolonged anti-infective therapy, especially in children.

Cytoreductive Surgery With Intraperitoneal Chemohyperthermia for the Treatment of Pseudomyxoma Peritonei: A Prospective Study

PURPOSEPseudomyxoma peritonei is a rare disease. Recently, cytoreductive surgery with intraperitoneal hyperthermic chemotherapy has emerged as a promising treatment for this debilitating condition. The aim of this prospective study was to evaluate this treatment strategy.METHODTwenty-seven patients with pseudomyxoma peritonei who were treated by cytoreductive surgery and intraperitoneal chemohyperthermia between 1997 and 2003 were identified from a prospective database.RESULTSClinical presentation included suspected appendicitis (33 percent), increased abdominal girth (30 percent), and a suspected ovarian mass (26 percent). Twenty-two patients underwent surgery elsewhere before referral. Seventeen complications occurred in 12 patients (44 percent). Six were considered major: three anastomotic leaks, two pleural effusions, and one intra-abdominal abscess. Histologic examination demonstrated Grade 1, 2, and 3 disease in 8 (30 percent), 10 (37 percent), and 9 patients (33 percent), respectively. Pathologic grade showed a significant influence on the complication rate (P = 0 0.008). The actuarial five-year survival was 100 percent for patients with Grade 1 disease, whereas actuarial one-, two-, three-, and five-year survival for Grades 2 and 3 were 100, 80, 64, and 32 percent, respectively (P = 0.008).CONCLUSIONSCytoreductive surgery with intraperitoneal hyperthermic chemotherapy is a feasable treatment for pseudomyxoma peritonei. It is associated with acceptable morbidity when performed by an experienced surgical team. Histologic grade is the major determinant of survival.

Peritoneal Mesothelioma Treated by Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy: Results of a Prospective Study

BackgroundPeritoneal mesothelioma is a rare disease with few therapeutic options. Recently, the combination of cytoreductive surgery with intraperitoneal hyperthermic chemotherapy (HIPEC) has shown promising results.MethodsFifteen patients with peritoneal mesothelioma who were treated by cytoreductive surgery and HIPEC between 1989 and 2004 were identified from a prospective database. HIPEC was performed with cisplatin and mitomycin C for 90 minutes by using the closed-abdomen technique.ResultsAll patients but one (multicystic) had malignant disease of the following pathologic types: 12 epithelial and 2 biphasic. After surgical resection, 11 patients were considered to have a CC-0 or CC-1 resection (macroscopic complete resection or diameter of residual nodules <2.5 mm). No postoperative death occurred, and six postoperative complications were recorded. All but one patient had resolution of ascites. The overall median survival for the 14 patients with malignant mesothelioma was 35.6 months. The median survival was 37.8 months for patients treated with a CC-0 or CC-1 resection, whereas it was 6.5 months for those treated with a CC-2 or CC-3 resection (diameter of residual nodules >2.5 mm; P < .001). In a univariate analysis, the only other significant prognostic factor was the carcinomatosis extent (P = .02).ConclusionsA therapeutic strategy combining cytoreductive surgery with HIPEC seems to provide an adequate and efficient locoregional treatment for peritoneal mesothelioma. It is associated with acceptable morbidity when performed by an experienced surgical team. The completeness of cytoreduction is the major determinant of survival.

Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial

BackgroundOpen transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma.Methods/DesignThe MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A.DiscussionPostoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery.Trial RegistrationNCT00937456 (ClinicalTrials.gov)

The impact of severe anastomotic leak on long-term survival and cancer recurrence after surgical resection for esophageal malignancy

Objective: The aim of this study was to the determine impact of severe esophageal anastomotic leak (SEAL) upon long-term survival and locoregional cancer recurrence. Background: The impact of SEAL upon long-term survival after esophageal resection remains inconclusive with a number of studies demonstrating conflicting results. Methods: A multicenter database for the surgical treatment of esophageal cancer collected data from 30 university hospitals (2000–2010). SEAL was defined as a Clavien-Dindo III or IV leak. Patients with SEAL were compared with those without in terms of demographics, tumor characteristics, surgical technique, morbidity, survival, and recurrence. Results: From a database of 2944 operated on for esophageal cancer between 2000 and 2010, 209 patients who died within 90 days of surgery and 296 patients with a R1/R2 resection were excluded, leaving 2439 included in the final analysis; 208 (8.5%) developed a SEAL and significant independent association was observed with low hospital procedural volume, cervical anastomosis, tumoral stage III/IV, and pulmonary and cardiovascular complications. SEAL was associated with a significant reduction in median overall (35.8 vs 54.8 months; P = 0.002) and disease-free (34 vs 47.9 months; P = 0.005) survivals. After adjustment of confounding factors, SEAL was associated with a 28% greater likelihood of death [hazard ratio = 1.28; 95% confidence interval (CI): 1.04–1.59; P = 0.022], as well as greater overall (OR = 1.35; 95% CI: 1.15–1.73; P = 0.011), locoregional (OR = 1.56; 95% CI: 1.05–2.24; P = 0.030), and mixed (OR = 1.81; 95% CI: 1.20–2.71; P = 0.014) recurrences. Conclusions: This large multicenter study provides strong evidence that SEAL adversely impacts cancer prognosis. The mechanism through which SEAL increases local recurrence is an important area for future research.

Impact of neoadjuvant chemoradiotherapy on postoperative outcomes after esophageal cancer resection: results of a European multicenter study.

Objectives:To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection. Background:Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL. Methods:Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n = 593) were compared with those treated by primary surgery (n = 1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics. Results:Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P = 0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P = 0.110) and 33.4% versus 32.1% (P = 0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P = 0.291), whereas chylothorax (2.5% vs 1.2%; P = 0.020), cardiovascular complications (8.6% vs 0.1%; P = 0.037), and thromboembolic events (8.6% vs 6.0%; P = 0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P = 0.228), with more chylothorax (2.5% vs 0.7%; P = 0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P = 0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT. Conclusions:Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).

Mucosal damage in the esophageal remnant after esophagectomy and gastric transposition.

Objective:To assess development of mucosal damage in the esophageal remnant in regard to the level of the esophagogastrostomy reconstruction either in a right chest or in a left neck position. Summary Background Data:Esophagectomy with gastric interposition creates an in vivo human model of pathologic esophageal reflux with the potential for long-term reflux disease complications. Methods:Eighty-four esophagectomy patients were assessed over time by symptoms, endoscopy and biopsies of their esophageal remnant after the operation. The anastomosis was in the right upper chest (n = 36) or in a left cervical position (n = 48). Visual quantification of damage, details of histopathology, and time period since surgery were recorded. Results:Twenty-nine patients (81%) with a right chest reconstruction had reflux symptoms when compared with 25 patients (53%) with a neck reconstruction (P = 0.007). Visualized reflux esophagitis was observed in 31 patients (81%) with chest anastomoses and in 22 patients (46%) with cervical anastomoses (P = 0.006). Documented mucosal damage and columnar lined metaplasia were significantly more frequent in the chest anastomosis group than the cervical group. The median of all mucosal damage and columnar lined metaplastic-free evolution were 13 ± 3 and 20.5 ± 6 months for the intrathoracic anastomosis, and 22 ± 6 months and 40 ± 8 months for the cervical anastomosis (P = 0.087). Two factors affecting the development of metaplasia were included in the multivariate analysis: an intrathoracic anastomosis (P = 0.018) and the presence of a previous Barrett esophagus (P = 0.064). Conclusions:When a gastric transplant is used after esophagectomy, a high prevalence of mucosal damage is observed in the esophageal remnant independently of the level of reconstruction. A left cervical anastomosis favors less reflux symptoms, less visualized damage, and delays the development of mucosal damage over time.

Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes

In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2‐way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN‐High, CIN‐Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K‐Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN‐Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development.

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer

Background:We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.Methods:Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.Results:Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.Conclusions:mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.

Laparoscopic Versus Open Surgery for Gastric Gastrointestinal Stromal Tumors: What Is the Impact on Postoperative Outcome and Oncologic Results?

OBJECTIVES The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs). BACKGROUND The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5 cm, remains unknown. METHODS Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20 cm (N = 666), by either laparoscopy (group L, n = 282) or open surgery (group O, n = 384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. RESULTS In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P = 0.086) and 11.3% vs 19.5% (P = 0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P = 0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P = 0.103). After 1:1 propensity score matching (n = 224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P = 0.005), surgical morbidity (4.9% vs 9.8%; P = 0.048), and medical morbidity (6.2% vs 13.4%; P = 0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P = 0.011). In tumors greater than 5 cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P = 0.255 and P = 0.423, respectively). CONCLUSIONS Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results.