While tumor-tissue remains the ‘gold standard’ for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, ...we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care.
Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients.
Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity.
Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.
Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine‐tryptophan‐ketoglutarate(HTK; N = ...8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL‐1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3‐year graft survival was higher with UW, IGL‐1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3‐year graft survival was 89% for IGL‐1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (−), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL‐1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL‐1 tends to offer the best graft outcome.
In a retrospective review of over 42,000 liver transplants perf ormed in Europe between 2003 and 2012 examining the use of either University of Wisconsin, histidine‐ tryptophan‐ketoglutarate (HTK), Celsior, or Institut Georges Lopez solution, the authors show that the use of HTK solution is an independent risk factor of graft loss. See editorial by Stewart on page 295.
Background
Laparoscopic right colectomy (LRC) has become a gold standard. However, a major current concern is still whether anastomosis should be performed extracorporeally or entirely ...laparoscopically. This meta-analysis assesses and compares peri- and postoperative outcomes of intracorporeal anastomosis (IA) versus extracorporeal anastomosis (EA) in LRC.
Methods
The research used the PubMed, Embase and Cochrane databases for studies comparing IA with EA during LRC. Our main endpoint was parietal abscess. Secondary endpoints were 30-day morbidity, mortality, time to onset of gas and stools, length of stay, number of lymph nodes removed and postoperative incisional hernia rates. The MINORS criteria were used to evaluate the quality of the studies examined.
Results
Twenty-four articles comprising 3699 patients, published between 2004 and 2020, were included in this meta-analysis. After sensitivity analysis, IA was associated with a decrease in parietal abscesses (OR 0.526, IC 0.333–0.832,
p
= 0.006).
Conclusion
This meta-analysis finds that IA allows a decrease in parietal abscesses and time to first gas and stools, surgical repair and length of stay, with similar overall complications.
Les cholangiocarcinomes sont des tumeurs digestives dont l’incidence reste faible et le pronostic sombre. Le bénéfice de la chimioradiothérapie adjuvante et de la radiothérapie n’a jamais été ...démontré dans un essai contrôlé randomisé de phase III. La chimiothérapie par capécitabine 6 mois est le traitement standard en situation adjuvante. La chimioradiothérapie est validé après exérèse R1. Elle n’est pas recommandée en situation néoadjuvante compte tenu du manque de données disponibles. La chimiothérapie et la chimioradiothérapie sont validées en situation adjuvante ou localement évoluée. La radiothérapie en conditions stéréotaxiques offre une perspective intéressante, au prix d’une toxicité digestive importante, nécessitant une évaluation dans le cadre d’essais randomisés.
Cholangiocarcinomas are digestive tumors whose incidence remains low and have poor prognosis. The benefits of adjuvant radiochemotherapy and radiotherapy have never been demonstrated in any phase III randomized controlled trial. Chemotherapy with capecitabine 6 months is the standard of care in adjuvant setting. Radiochemotherapy is validated in R1 patients. It is not recommended in neoadjuvant situations given the lack of evidence. Chemotherapy and radiochemotherapy are validated in adjuvant or locally advanced diseases. Stereotactic radiation therapy offers an interesting perspective, at the cost of significant digestive toxicities, requiring evaluation in randomized trials.
Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the ...reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network.
From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC).
All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033).
This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.
Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a ...competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC.
This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate.
There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval CI: 0.81–1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm.
Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.
Summary Background & aims Malnutrition is frequent in head and neck (HN) and esophageal cancer patients and aggravated by radiochemotherapy (RCT), increasing morbi-mortality and treatment toxicity. ...Our goal was to investigate the effect of immunonutrition consisting of an arginine, omega-3 fatty acid, nucleotides-enriched diet on nutritional status, and functional capacity in HN or esophageal cancer patients undergoing RCT. Methods 37 patients were randomized in a double-blind clinical trial. 5 days before and until the end of RCT (5–7 weeks), they received either an Immunomodulating Enteral Nutrition (IEN) or an isonitrogenous, isoenergetic Standard Enteral Nutrition (SEN). Anthropometrical parameters, nutritional risk index (NRI), serum albumin, plasma antioxidant capacity, and functional capacity were recorded between the beginning and the end of RCT. Results A significant gain in total body weight (+2.1 ± 3.1 kg) was observed in IEN patients. Albuminemia and NRI were improved concomitantly in IEN malnourished patients. Plasma antioxidant capacity was improved (+100 ± 13 μM Eq Trolox) in IEN patients. Functional capacity measured by WHO Performance Status and Karnofsky index was maintained in IEN patients but significantly reduced in SEN patients. Conclusions These preliminary data show that immunonutrition could improve the nutritional status together with functional capacity in HN and esophageal cancer patients undergoing RCT. Clinical trial registration This clinical trial promoted by the University Hospital Center of Clermont-Ferrand has been registered at ClinicalTrial.gov website under the following reference: NCT00333099.
Robotic-assisted surgery (RAS) is becoming increasingly important in colorectal surgery. Recognition of the short, safe learning curve (LC) could potentially improve implementation. We evaluated the ...extent and safety of the LC in robotic resection for rectal cancer.
Consecutive rectal cancer resections (January 2018 to February 2021) were prospectively included from three French centres, involving nine surgeons. LC analyses only included surgeons who had performed more than 25 robotic rectal cancer surgeries. The primary endpoint was operating time LC and the secondary endpoint conversion rate LC. Interphase comparisons included demographic and intraoperative data, operating time, conversion rate, pathological specimen features and postoperative morbidity.
In 174 patients (69% men; mean age 62.6 years) the mean operating time was 334.5 ± 92.1 min. Operative procedures included low anterior resection (n = 143) and intersphincteric resection (n = 31). For operating time, there were two or three (centre-dependent) LC phases. After 12-21 cases (learning phase), there was a significant decrease in total operating time (all centres) and an increase in the number of harvested lymph nodes (two centres). For conversion rate, there were two or four LC phases. After 9-14 cases (learning phase), the conversion rate decreased significantly in two centres; in one centre, there was a nonsignificant decrease despite the treatment of significantly more obese patients and patients with previous abdominal surgery. There were no significant differences in interphase comparisons.
The LC for RAS in rectal cancer was achieved after 12-21 cases for the operating time and 9-14 cases for the conversion rate. RAS for rectal cancer was safe during this time, with no interphase differences in postoperative complications and circumferential resection margin.
Le tissu adipeux (TA) blanc est un organe endocrine jouant un rôle important dans le métabolisme et sur la composition corporelle. Contrairement au muscle squelettique, son activité énergétique ...mitochondriale a été peu étudiée, mais de récentes études semblent établir des liens entre des tableaux cliniques de patients à indice de masse corporelle (IMC) bas (<20kg·m−2) ou à l’inverse élevés (>30kg·m−2) et une modification du métabolisme mitochondrial de leur TA. Chez les patients obèses, celui-ci serait ralenti alors qu’il serait à l’inverse accéléré chez des patients atteints de maigreur constitutionnelle.
L’étude clinique OxMiTiAd (ClinicalTrials.gov Identifier : NCT05417581) a pour but d’évaluer la relation entre l’IMC et la respiration mitochondriale des tissus adipeux sous-cutané et viscéral humains. Les hypothèses de ce travail sont (1) qu’il existe une relation entre les paramètres mitochondriaux, l’IMC et la quantité de tissu adipeux ; (2) que la fonction mitochondriale est dépendante de la localisation tissulaire du dépôt de TA.
À date, 41 patient(e)s (25 hommes et 16 femmes) éligibles pour une chirurgie digestive (CHU Clermont-Ferrand) ont été inclus(es) dans l’étude avec des IMC compris entre 15,1 et 35,5kg·m−2. Ils/elles ont principalement été référé(e)s pour une chirurgie oncologique (38/41). Dans le cadre du bilan de ces patients, des coupes scanner en L3 ont été réalisées et seront utilisées pour évaluer leur composition corporelle. Sur le temps opératoire, des biopsies de TA sous-cutané et viscéral ont été prélevées afin de caractériser la fonction mitochondriale in situ par respirométrie haute résolution (O2k Oxygraph, OROBOROS). Après perméabilisation à la digitonine des adipocytes, la mesure de la respiration mitochondriale est réalisée par ajouts successifs de substrats et d’inhibiteurs des complexes de la chaine respiratoire mitochondriale.
Les résultats préliminaires montrent une corrélation négative entre la respiration mitochondriale maximale (Vmax) et l’IMC (p<0,05) indépendamment de la localisation tissulaire. Une corrélation négative est également observée entre la Vmax du TA sous-cutané et la quantité de TA sous-cutané (p<0,01) ainsi qu’entre la Vmax du TA viscéral et la quantité de TA viscéral (p<0,05). La respiration mitochondriale est significativement supérieure dans le TA viscéral par rapport au TA sous-cutané pour tous les états respiratoires étudiés (p<0,05). Il n’y a pas de différence de respiration mitochondriale entre les hommes et les femmes, quel que soit le TA et l’état respiratoire étudiés.
En conclusion, la fonction mitochondriale est corrélée à l’IMC et à la quantité de TA sous-cutané et viscéral. Il est également observé une respiration mitochondriale maximale plus importante du TA viscéral par rapport au TA sous-cutané. Des analyses complémentaires permettront de déterminer si les différences sont d’ordre quantitatif et/ou qualitatif.
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