[Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. / La chimiothérapie intra-péritonéale dans le traitement de la carcinose péritonéale d'origine colorectale. CHIP, PIPAC, état des lieux et perspectives.

After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.

Laparoscopic cytoreductive surgery and HIPEC in LAMN with small volume of peritoneal disease: a valuable option of treatment for good patient-related experience measures (PREMs).

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the best effective treatment for pseudomyxoma peritonei (PMP). In the last years, the advances in histopathology have stratified PMP lesions in different degrees of aggressivity suggesting the possibility of a tailored treatment. In a subset of patients with small volume peritoneal disease, laparoscopic CRS and HIPEC is feasible. The aim of this study is to analyze the results of laparoscopic CRS + HIPEC in a monocentric series of patients under patient-related experience measures (PREMs). METHODS: All consecutive patients who underwent laparoscopic CRS-HIPEC with curative intent at Cancer Institute of Montpellier were retrieved from a prospectively maintained database and analyzed. Selection criteria for laparoscopic approach were low-grade PMP with pathological confirmation prior to CRS-HIPEC, age < 75 years, no extra-peritoneal disease, peritoneal cancer index (PCI) < 10, and a limited history of abdominal surgery. A PREMS interview was conducted before analysis with all the included patients. Outcomes of interest included postoperative morbidity, medium-term survival, and PREMs. RESULTS: Fourteen patients were operated on for low-grade PMP with a laparoscopic approach at our institution. Conversions to laparotomy were necessary in three patients, and postoperative complications were observed in three patients (Clavien 3b in one patient). In-hospital postoperative median stay was 9.5 days. No death or recurrence was observed during the study period. CONCLUSIONS: Laparoscopic CRS-HIPEC for LAMN in presence of small peritoneal disease is feasible in terms of postoperative morbidity and mortality. According to our PREMs questionnaire, patients' expectations were satisfied.

Complete pathologic response after two-stage cytoreductive surgery with HIPEC for bulky pseudomyxoma peritonei: proof of concept.

Introduction: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the progressive accumulation of mucinous ascites and peritoneal implants. The optimal treatment for PMP includes the association of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). For patients with a large burdensome disease, the completeness of cytoreduction sometimes requires maximal effort surgery. The aim of this article is to provide proof of concept for two stage cytoreductive surgery (CRS) in this category of patients.Methods and materials: A two stage CRS and HIPEC with oxaliplatin was proposed for patients with bulky PMP including important involvement of the serosal surfaces of the bowel or colon who had an impaired nutritional status. The residual disease at the end of the first stage was less than 5 mm of thickness on several implants. Clinical, surgical and histopathological variables were analyzed.Results: All eight patients completed the two-stage strategy. Mortality was nil. One Clavien Dindo grade 3 event occurred in each stage. After a median follow up of 29.5 months, all patients were alive and free of recurrence. All of the patients had histopathological complete response on the specimens obtained from the residual sites during the second stage surgery.Conclusions: Two-stage surgical strategy is feasible for bulky PMP patients and it is associated with little high-grade morbidity and enhanced visceral sparing.

The sunflower genome provides insights into oil metabolism, flowering and Asterid evolution.

The domesticated sunflower, Helianthus annuus L., is a global oil crop that has promise for climate change adaptation, because it can maintain stable yields across a wide variety of environmental conditions, including drought. Even greater resilience is achievable through the mining of resistance alleles from compatible wild sunflower relatives, including numerous extremophile species. Here we report a high-quality reference for the sunflower genome (3.6 gigabases), together with extensive transcriptomic data from vegetative and floral organs. The genome mostly consists of highly similar, related sequences and required single-molecule real-time sequencing technologies for successful assembly. Genome analyses enabled the reconstruction of the evolutionary history of the Asterids, further establishing the existence of a whole-genome triplication at the base of the Asterids II clade and a sunflower-specific whole-genome duplication around 29 million years ago. An integrative approach combining quantitative genetics, expression and diversity data permitted development of comprehensive gene networks for two major breeding traits, flowering time and oil metabolism, and revealed new candidate genes in these networks. We found that the genomic architecture of flowering time has been shaped by the most recent whole-genome duplication, which suggests that ancient paralogues can remain in the same regulatory networks for dozens of millions of years. This genome represents a cornerstone for future research programs aiming to exploit genetic diversity to improve biotic and abiotic stress resistance and oil production, while also considering agricultural constraints and human nutritional needs.

Genetic control of plasticity of oil yield for combined abiotic stresses using a joint approach of crop modelling and genome-wide association.

Understanding the genetic basis of phenotypic plasticity is crucial for predicting and managing climate change effects on wild plants and crops. Here, we combined crop modelling and quantitative genetics to study the genetic control of oil yield plasticity for multiple abiotic stresses in sunflower. First, we developed stress indicators to characterize 14 environments for three abiotic stresses (cold, drought and nitrogen) using the SUNFLO crop model and phenotypic variations of three commercial varieties. The computed plant stress indicators better explain yield variation than descriptors at the climatic or crop levels. In those environments, we observed oil yield of 317 sunflower hybrids and regressed it with three selected stress indicators. The slopes of cold stress norm reaction were used as plasticity phenotypes in the following genome-wide association study. Among the 65 534 tested Single Nucleotide Polymorphisms (SNPs), we identified nine quantitative trait loci controlling oil yield plasticity to cold stress. Associated single nucleotide polymorphisms are localized in genes previously shown to be involved in cold stress responses: oligopeptide transporters, lipid transfer protein, cystatin, alternative oxidase or root development. This novel approach opens new perspectives to identify genomic regions involved in genotype-by-environment interaction of a complex traits to multiple stresses in realistic natural or agronomical conditions.