Regional differences in prostaglandin E₂ metabolism in human colorectal cancer liver metastases

Background: Prostaglandin (PG) E₂ plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE₂ catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE₂ content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE₂ in human CRC cells in vitro. Methods: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE₂ levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β. Results: PGE₂ levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE₂. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.Conclusions: There is significant intra-tumoral heterogeneity in PGE₂ content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE₂ metabolism should be targeted for novel treatment of advanced CRC

Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy±radiotherapy±hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt–PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff–Bloom–Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P=0.0005) and high SBR grade (P=0.003), size ⩾5 cm (P=0.038), high T stage (P=0.013), presence of intravascular embolus (P=0.034), and >3 N+ (P=0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer

Does conversion during minimally invasive rectal surgery for cancer have an impact on short-term and oncologic outcomes? Results of a retrospective cohort study

Background: Although minimally invasive rectal surgery (MIRS) for cancer provides better recovery for similar oncologic outcomes over open approach, conversion is still required in 10% and its impact on short-term and long-term outcomes remains unclear. The aim of our study was to evaluate the impact of conversion on postoperative and oncologic outcomes in patients undergoing MIRS for cancer. Methods: From June 2011 to March 2020, we reviewed 257 minimally invasive rectal resections for cancer recorded in a prospectively maintained database, with 192 robotic and 65 laparoscopic approaches. Patients who required conversion to open (Conversion group) were compared to those who did not have conversion (No conversion group) in terms of short-term, histologic, and oncologic outcomes. Univariate and multivariate analyses of the risk factors for postoperative morbidity were performed. Results: Eighteen patients (7%) required conversion. The conversion rate was significantly higher in the laparoscopic approach than in the robotic approach (16.9% vs 3.6%, p < 0.01). Among the 4 reactive conversions, 3 (75%) were required during robotic resections. Patients in the Conversion group had a higher morbidity rate (83.3% vs 43.1%, p = 0.01) and more severe complications (38.9%, vs 18.8%, p = 0.041). Male sex [HR = 2.46, 95%CI (1.41–4.26)], total mesorectal excision [HR = 2.89, 95%CI (1.57–5.320)], and conversion (HR = 4.87, 95%CI [1.34–17.73]) were independently associated with a higher risk of overall 30-day morbidity. R1 resections were more frequent in the Conversion group (22.2% vs 5.4%, p = 0.023) without differences in the overall (82.7 ± 7.0 months vs 79.4 ± 3.3 months, p = 0.448) and disease-free survivals (49.0 ± 8.6 months vs 70.2 ± 4.1 months, p = 0.362). Conclusion: Conversion to laparotomy during MIRS for cancer was associated with poorer postoperative results without impairing oncologic outcomes. The high frequency of reactive conversion due to intraoperative complications in robotic resections confirmed that MIRS for cancer is a technically challenging procedure

Endoscopic management of pancreatic fistula after distal pancreatectomy and enucleation

BACKGROUND: Preoperative endoscopic pancreatic sphincterotomy (EPS) has been proposed to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) or enucleation (EN). The use of EPS as a curative treatment for POPF has been scarcely reported. We reported 10 consecutive patients who were successfully treated by EPS for a prolonged POPF. STUDY DESIGN: Ten patients underwent EPS for prolonged POPF (median duration = 40 days, range 20-114; median daily output = 80 mL, range 50-250) after 6 DPs, 2 ENs, and 2 medial pancreatectomies. RESULTS: EPS was performed in all patients, with stent insertion in 4. No patient developed a specific complication because of EPS. POPF healed within a median delay of 4 days (range 1-12). One patient underwent a repeated endoscopy to treat stent malposition. The median delay of discharge after EPS was 13 days (range 8-15). With a 20-month median follow up, 1 patient developed early transient POPF recurrence because of spontaneous stent migration. CONCLUSIONS: EPS is indicated for prolonged POPF after DP or EN because it is highly feasible, shortens healing, and is well tolerated

Quel est le score échographique des glandes salivaires le plus efficace pour diagnostiquer un syndrome de Gougerot-Sjögren primitif ou secondaire ?

National audienceObjectif Évaluer la performance de l’échographie des glandes salivaires pour le diagnostic du syndrome de Gougerot-Sjögren primitif (SGSp) ou secondaire (SGSs). Méthodes Étude transversale multicentrique sur 97 patients présentant un syndrome sec clinique. Le SGSp (n = 39) et le SGSs (n = 22) remplissaient les critères de classification du groupe de consensus américano-européen (AECG, American-European Consensus Group). Les témoins (n = 36) étaient des patients présentant un syndrome sec mais ne remplissant pas les critères de l’AECG. L’échostructure des quatre glandes salivaires principales a été évaluée selon quatre méthodes : le score de Salaffi (0–16), le score de Jousse-Joulin (0–4), le score de Hocevar (0–48) et le score de Milic (0–12). Résultats Les résultats médians des scores échographiques étaient plus élevés dans les groupes SGSp et SGSs que chez les témoins (p < 0,001). Selon les courbes ROC et le rapport de vraisemblance positif (RV + ), les quatre scores ont montré une bonne performance diagnostique pour le SGSp et le SGSs. L’aire sous la courbe (ASC) du SGSp et du SGSs était respectivement de 0,891 (IC 95 % 0,812–0,970) et de 0,824 (IC 95 % 0,695–0,954) pour le score de Hocevar, de 0,885 (IC 95 % 0,804–0,965) et de 0,808 (IC 95 % 0,673–0,943) pour le score de Milic, de 0,915 (IC 95 % 0,848–0,982) et de 0,844 (IC 95 % 0,724–0,965) pour le score de Salaffi et de 0,897 (IC 95 % 0,821–0,973) et de 0,851 (IC 95 % 0,735–0,968) pour le score de Jousse-Joulin. Cette étude a mis en évidence une reproductibilité interobservateur intéressante (kappa 0,714 ± 0,131) de l’évaluation échographique, avec un accord entre les lecteurs de 85,7 % pour la détermination du caractère pathologique des glandes salivaires. Conclusion L’échographie des glandes salivaires est une procédure d’imagerie simple, non invasive et performante pour le diagnostic du SGSp et du SGSs selon les scores de Salaffi, de Milic et de Jousse-Joulin

Robotic-assisted right colectomy. Official expert recommendations delivered under the aegis of the French Association of Surgery (AFC)

: Twenty-seven experts under the aegis of the French Association of Surgery (AFC) offer this reference system with formalized recommendations concerning the performance of right colectomy by robotic approach (RRC). For RRC, experts suggest patient installation in the so-called "classic" or "suprapubic" setup. For patients undergoing right colectomy for a benign pathology or cancer, RRC provides no significant benefit in terms of intra-operative blood loss, intra-operative complications or conversion rate to laparotomy compared to laparoscopy. At the same time, RRC is associated with significantly longer operating times. Data from the literature are insufficient to define whether the robot facilitates the performance of an intra-abdominal anastomosis, but the robotic approach is more frequently associated with an intra-abdominal anastomosis than the laparoscopic approach. Experts also suggest that RRC offers a benefit in terms of post-operative morbidity compared to right colectomy by laparotomy. No benefit is retained in terms of mortality, duration of hospital stay, histological results, overall survival or disease-free survival in RRC performed for cancer. In addition, RRC should not be performed based on the cost/benefit ratio, since RRC is associated with significantly higher costs than laparoscopy and laparotomy. Future research in the field of RRC should consider the evaluation of patient-targeted parameters such as pain or quality of life and the technical advantages of the robot for complex procedural steps, as well as surgical and oncological results

Colectomie droite par abord robotique. Recommandations formalisées d’experts sous l’égide de l’Association française de chirurgie (AFC)

Twenty-seven experts under the aegis of the French Association of Surgery (AFC) offer this reference system with formalized recommendations concerning the performance of right colectomy by robotic approach (RRC). For RRC, experts suggest patient installation in the so-called “classic” or “suprapubic” setup. For patients undergoing right colectomy for a benign pathology or cancer, RRC provides no significant benefit in terms of intra-operative blood loss, intra-operative complications or conversion rate to open laparotomy compared to laparoscopy. At the same time, RRC is associated with significantly longer operating times. Data from the literature are insufficient to define whether the robot facilitates the performance of an intra-abdominal anastomosis, but the robotic approach is more frequently associated with an intra-abdominal anastomosis than the laparoscopic approach. Experts also suggest that RRC offers a benefit in terms of post-operative morbidity compared to right colectomy by laparotomy. No benefit is retained in terms of mortality, duration of hospital stay, histological results, overall survival or recurrence-free survival in RRC performed for cancer. In addition, RRC should not be performed based on the cost/benefit ratio, since RRC is associated with significantly higher costs than laparoscopy and laparotomy. Future research in the field of RRC should consider the evaluation of patient-targeted parameters such as pain or quality of life and the technical advantages of the robot for complex procedural steps, as well as surgical and oncological results