Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin.

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients.

[Intraperitoneal therapy for carcinomatosis in ovarian cancer: proposed treatment algorithm]. / Traitements intrapéritonéaux de la carcinose ovarienne : proposition d'algorithmes décisionnels.

Ovarian cancer is the first cause of death by gynecological cancer. Most of the patients are diagnosed with peritoneal carcinomatosis that represents a therapeutic challenge. Its management implies maximal cytoreductive surgery with survival benefit. Over the last three decades, several strategies of intra-peritoneal chemotherapy have been investigated. This includes intra-peritoneal adjuvant chemotherapy that is used mainly in North America, hyperthermic intraperitoneal chemotherapy (HIPEC) and more recently pressurized intraperitoneal aerosol chemotherapy (PIPAC). In the current article, we review the evidence in favor of each therapeutic approach, and we propose treatment algorithms depending on the clinical situation of ovarian cancer patients: upfront, platinum-sensitive and platinum-resistant relapse.

Le cancer de l'ovaire est la première cause de décès par cancer gynécologique. La plupart des patientes sont diagnostiquées au stade de carcinose péritonéale qui représente un défi thérapeutique. Sa prise en charge chirurgicale implique une cytoréduction maximaliste. Au cours des 30 dernières années, plusieurs stratégies de chimiothérapie intrapéritonéale ont été testées afin d'améliorer le contrôle de la carcinose péritonéale. Il s'agit des chimiothérapies intrapéritonéale adjuvante utilisée surtout en Amérique du Nord, hyperthermique intrapéritonéale (CHIP) et intrapéritonéale pressurisée en aérosols (PIPAC). Dans cet article, nous reprenons les données de la littérature sur chacune de ces trois approches thérapeutiques et proposons des algorithmes décisionnels selon la situation clinique des patientes traitées pour un cancer de l'ovaire : au diagnostic, récidive platine-sensible et platine-résistante.

Limited Resection Versus Pancreaticoduodenectomy for Duodenal Gastrointestinal Stromal Tumors? Enucleation Interferes in the Debate: A European Multicenter Retrospective Cohort Study.

BACKGROUND: The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate. OBJECTIVES: The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN). METHODS: In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated. RESULTS: Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p < 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors < 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences. CONCLUSIONS: For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed.

Depletion of MUC5B mucin in gastrointestinal cancer cells alters their tumorigenic properties: implication of the Wnt/ß-catenin pathway.

Secreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosae in normal adults. Alteration of their expression is a hallmark of numerous epithelial cancers and has often been correlated to bad prognosis of the tumour. The secreted mucin MUC5B is overexpressed in certain subtypes of gastric and intestinal cancers, but the consequences of this altered expression on the cancer cell behaviour are not known. To investigate the role of MUC5B in carcinogenesis, its expression was knocked-down in the human gastric cancer cell line KATO-III and in the colonic cancer cell line LS174T by using transient and stable approaches. Consequences of MUC5B knocking-down on cancer cells were studied with respect to in vitro proliferation, migration and invasion, and in vivo on tumour growth using a mouse subcutaneous xenograft model. Western blotting, luciferase assay and qRT-PCR were used to identify proteins and signalling pathways involved. In vitro MUC5B down-regulation leads to a decrease in proliferation, migration and invasion properties in both cell lines. Molecular mechanisms involved the alteration of ß-catenin expression, localization and activity and decreased expression of several of its target genes. In vivo xenografts of MUC5B-deficient cells induced a decrease in tumour growth when compared with MUC5B-expressing Mock cells. Altogether, the present study shows that down-regulation of MUC5B profoundly alters proliferation, migration and invasion of human gastrointestinal cancer cells and that these alterations may be, in part, mediated by the Wnt/ß-catenin pathway emphasizing the potential of MUC5B as an actor of gastrointestinal carcinogenesis.