Root cause analysis of mortality after esophagectomy for cancer: a multicenter cohort study from the FREGAT database.

BACKGROUND: Esophagectomy is associated with significant mortality. A better understanding of the causes leading to death may help to reduce mortality. A root cause analysis of mortality after esophagectomy was performed. METHODS: Root cause analysis was retrospectively applied by an independent expert panel of 4 upper gastrointestinal surgeons and 1 anesthesiologist-intensivist to patients included in the French national multicenter prospective cohort FREGAT between August 2014 and September 2019 who underwent an esophagectomy for cancer and died within 90 days of surgery. A cause-and-effect diagram was used to determine the root causes related to death. Death was classified as potentially preventable or non-preventable. RESULTS: Among the 1,040 patients included in the FREGAT cohort, 70 (6.7%) patients (male: 81%, median age 68 [62-72] years) from 17 centers were included. Death was potentially preventable in 37 patients (53%). Root causes independently associated with preventable death were inappropriate indication (odds ratio 35.16 [2.50-494.39]; P = .008), patient characteristics (odds ratio 5.15 [1.19-22.35]; P = .029), unexpected intraoperative findings (odds ratio 18.99 [1.07-335.55]; P = .045), and delay in diagnosis of a complication (odds ratio 98.10 [6.24-1,541.04]; P = .001). Delay in treatment of a complication was found only in preventable deaths (28 [76%] vs 0; P < .001). National guidelines were less frequently followed (16 [43%] vs 22 [67%]; P = .050) in preventable deaths. The only independent risk factor of preventable death was center volume <26 esophagectomies per year (odds ratio 4.71 [1.55-14.33]; P = .006). CONCLUSIONS: More than one-half of deaths after esophagectomy were potentially preventable. Better patient selection, early diagnosis, and adequate management of complications through centralization could reduce mortality.

Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P<0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous (P=0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P=0.977) and location (P=0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P=0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.

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.

Recurrence After Surgery for Primary Hyperparathyroidism in 517 Patients With Multiple Endocrine Neoplasia Type 1: An Association Francophone de Chirurgie Endocrinienne and Groupe d'étude des Tumeurs Endocrines study.

OBJECTIVE: To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery. BACKGROUND: In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence. METHODS: MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded. RESULTS: Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016). CONCLUSIONS: Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated.

The association of benzodiazepine and benzodiazepine-related drugs with outcomes after surgery for colorectal cancer.

Benzodiazepines increase plasma brain-derived neurotrophic factor (BDNF) level which, in turn, may improve survival in colorectal cancer (CRC) patients. This study aimed to evaluate the associations between benzodiazepine and benzodiazepine-related drugs (BZRD) use and outcomes of patients operated for CRC. This is a retrospective cohort study including patients operated for CRC at Limoges' University Hospital between 2010 and 2019. Data were collected from two sources: medical records of patients in the digestive, general and endocrine surgery department at Limoges University Hospital and from the Haute-Vienne general cancer registry. Patients were divided into benzodiazepine users and non-users. Outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 504 patients who underwent surgery for CRC, 125 (24.8%) patients were treated with benzodiazepine/BZRD drugs. Users and non-users of benzodiazepine/BZRD showed no statistically significant differences in 5-year OS (45.5 ± 1.9% vs. 46.5 ± 1.1% p = 0.25) and 5-year RFS (41.0 ± 2.1% vs. 39.6 ± 1.3%, p = 0.94), even after adjustment for confounders and propensity score (OS: aHR=1.02, 95%CI: 0.71-1.48; RFS: aHR=1.00, 95%CI: 0.72-1.40). Subgroup analysis on CRC patients with psychiatric disorders revealed that benzodiazepine users had better RFS (aHR=0.58, 95%CI: 0.35-0.96) compared with non-users, particularly, patients with stages III or IV of CRC had better OS (aHR=0.27; 95%CI: 0.12-0.59) and RFS (aHR=0.30, 95%CI: 0.15-0.62). OS and RFS was significantly better in patients taking benzodiazepines classified as anxiolytics, having longer half-life, and producing active metabolites. In conclusion, benzodiazepine use was not associated with outcomes in CRC patients. Nevertheless, in subgroup of patients with psychiatric disorders and advanced CRC stage, benzodiazepine could improve survival.

Robotic surgery for inguinal and ventral hernia repair: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis assessed the effectiveness of robotic surgery compared to laparoscopy or open surgery for inguinal (IHR) and ventral (VHR) hernia repair. METHODS: PubMed and EMBASE were searched up to July 2022. Meta-analyses were performed for postoperative complications, surgical site infections (SSI), seroma/hematoma, hernia recurrence, operating time (OT), intraoperative blood loss, intraoperative bowel injury, conversion to open surgery, length of stay (LOS), mortality, reoperation rate, readmission rate, use of opioids, time to return to work and time to return to normal activities. RESULTS: Overall, 64 studies were selected and 58 were used for pooled data analyses: 35 studies (227 242 patients) deal with IHR and 32 (158 384 patients) with VHR. Robotic IHR was associated with lower hernia recurrence (OR 0.54; 95%CI 0.29, 0.99; I2: 0%) compared to laparoscopic IHR, and lower use of opioids compared to open IHR (OR 0.46; 95%CI 0.25, 0.84; I2: 55.8%). Robotic VHR was associated with lower bowel injuries (OR 0.59; 95%CI 0.42, 0.85; I2: 0%) and less conversions to open surgery (OR 0.51; 95%CI 0.43, 0.60; I2: 0%) compared to laparoscopy. Compared to open surgery, robotic VHR was associated with lower postoperative complications (OR 0.61; 95%CI 0.39, 0.96; I2: 68%), less SSI (OR 0.47; 95%CI 0.31, 0.72; I2: 0%), less intraoperative blood loss (- 95 mL), shorter LOS (- 3.4 day), and less hospital readmissions (OR 0.66; 95%CI 0.44, 0.99; I2: 24.7%). However, both robotic IHR and VHR were associated with significantly longer OT compared to laparoscopy and open surgery. CONCLUSION: These results support robotic surgery as a safe, effective, and viable alternative for IHR and VHR as it can brings several intraoperative and postoperative advantages over laparoscopy and open surgery.

Surgery for Primary Aldosteronism in France From 2010 to 2020 - Results from the French-Speaking Association of Endocrine Surgery (AFCE): Eurocrine Study Group.

OBJECTIVE: Describe the diagnostic workup and postoperative results for patients treated by adrenalectomy for primary aldosteronism in France from 2010 to 2020. BACKGROUND: Primary aldosteronism (PA) is the underlying cause of hypertension in 6% to 18% of patients. French and international guidelines recommend CT-scan and adrenal vein sampling as part of diagnostic workup to distinguish unilateral PA amenable to surgical treatment from bilateral PA that will require lifelong antialdosterone treatment.Adrenalectomy for unilateral primary aldosteronism has been associated with complete resolution of hypertension (no antihypertensive drugs and normal ambulatory blood pressure) in about one-third of patients and complete biological success in 94% of patients.These results are mainly based on retrospective studies with short follow-up and aggregated patients from various international high-volume centers. METHODS: Here we report results from the French-Speaking Association of Endocrine Surgery (AFCE) using the Eurocrine® Database. RESULTS: Over 11 years, 385 patients from 10 medical centers were eligible for analysis, accounting for >40% of adrenalectomies performed in France for primary aldosteronism over the period.Preoperative workup was consistent with guidelines for 40% of patients. Complete clinical success (CCS) at the last follow-up was achieved in 32% of patients, and complete biological success was not sufficiently assessed.For patients with 2 follow-up visits, clinical results were not persistent at 1 year for one-fifth of patients.Factors associated with CCS on multivariate analysis were body mass index, duration of hypertension, and number of antihypertensive drugs. CONCLUSIONS: These results call for an improvement in thorough preoperative workup and long-term follow-up of patients (clinical and biological) to early manage hypertension and/or PA relapse.

First Case of Abdominal and Tunica Vaginalis Multicystic Benign Mesothelioma: Management and Review of Literature.

Multicystic benign mesothelioma is a rare tumor that affects the serosa. Most cases present with peritoneal lesions exclusively. Some identified risk factors are chronic abdominal inflammation, woman of childbearing age, and asbestos exposure. The symptomatology is not specific and can delay the diagnosis. There are no guidelines for the treatment of this pathology. We describe one male patient with abdominal and tunica vaginalis localizations of multicystic benign mesothelioma. The diagnosis was suspected on imaging and confirmed with histological examination. The treatment on an expert center was complete cytoreduction surgery and HIPEC, but the patient had two recurrences during the 2-year of follow-up. This is the first case of simultaneous rare localizations of multicystic benign mesothelioma. No new risk factors were identified. The case underlines the importance of regular examination of all serosa localizations.

Ambulatory thyroidectomy. Recommendations of the Association francophone de chirurgie endocrinienne (AFCE), with the Société française d'endocrinologie (SFE) and the Société française de médecine nucléaire (SFMN).

Before ambulatory thyroidectomy is proposed, the patient and his family and/or friends will need to be informed by the surgeon of the specificity of this procedure, the normal postoperative effects of a thyroidectomy, and potential complications. Also known as outpatient thyroid surgery, it can only be proposed by an experienced surgeon supported by an adequately trained medical and paramedical team. The healthcare establishment must be in possession of all the resources needed in ambulatory management, with continuity of care guaranteed 24h/24 7d/7 in the event of possible emergency rehospitalization. In all cases, contact the day after the operation between the healthcare facility and the patient is imperative. Ambulatory management can be proposed for lobo-isthmectomy or isthmectomy, possibly involving lymph node dissection. It is also possible for secondary totalization of thyroidectomy (following lobectomy). On the other hand, indications for single-stage total thyroidectomy must be limited and ensure proximity between the patient's home and a healthcare structure with a platform adapted to the pathology necessitating surgical intervention (non-plunging euthyroid goiter). A precise clinical pathway must be set out, including pre-, peri- and postoperative protocols having been formalized for surgery (hemostasis procedures) and for anesthesia (prevention of pain, of vomiting and of hypertension). We recommend at least 6hours of postoperative surveillance in outpatient care. When outpatient treatment is not possible or not recommended, hospitalization stay after thyroidectomy can be limited to 24hours, except in the event of postoperative complications, or a need for effectively dosed anticoagulant treatment.

Pancreatoduodenectomy Following Preoperative Biliary Drainage Using Endoscopic Ultrasound-Guided Choledochoduodenostomy Versus a Transpapillary Stent: A Multicenter Comparative Cohort Study of the ACHBT-FRENCH-SFED Intergroup.

BACKGROUND: It is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). METHODS: Patients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. RESULTS: Among 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups. CONCLUSIONS: PBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.

Job Strain, Burnout, and Suicidal Ideation in Tenured University Hospital Faculty Staff in France in 2021.

Importance: The ability to attract and retain university hospital faculty staff is in jeopardy because of the high levels of mental symptoms in this professional group. Objective: To examine the prevalence and determinants of symptoms of severe burnout, job strain, and suicidal ideation in tenured associate and full professors in university hospitals. Design, Setting, and Participants: This nationwide cross-sectional study offered online surveys to 5332 tenured university hospital faculty members in France from October 25, 2021, to December 20, 2021. Exposures: Burnout and job strain. Main Outcomes and Measures: Participants completed the 22-item Maslach Burnout Inventory and a 12-item job strain assessment tool, reported suicidal ideation, and used visual analog scales to evaluate unidimensional parameters. The primary outcome was presence of severe burnout symptoms. Factors associated with mental health symptoms were identified by multivariable logistic regression. Results: Completed questionnaires were returned by 2390 of 5332 faculty members (response rate, 45%; range, 43%-46%). Tenured associate professors were a median of 40 (IQR, 37-45) years old with a sex ratio of 1:1, whereas tenured full professors were a median of 53 (IQR, 46-60) years old with a sex ratio of 1:5. Of 2390 respondents, 952 (40%) reported symptoms of severe burnout. Symptoms of job strain (296 professors [12%]) and suicidal ideation (343 professors [14%]) were also reported. Compared with full professors, significantly more associate professors reported feeling overwhelmed at work (496 [73%] vs 972 [57%]; P < .001), considering resignation (365 [54%] vs 834 [49%]; P = .004), or considering a career change (277 [41%] vs 496 [29%]; P < .001). Factors independently associated with less burnout were a longer time being a professor (adjusted odds ratio [aOR], 0.97; 95% CI, 0.96-0.98 per year of age), sleeping well (aOR, 0.88; 95% CI, 0.83-0.92), feeling valued by colleagues (aOR, 0.91; 95% CI, 0.86-0.95 per visual analog scale point) or the public (aOR, 0.92; 95% CI, 0.88-0.96 per visual analog scale point), and accepting more tasks (aOR, 0.82; 95% CI, 0.72-0.93). Factors independently associated with more burnout were having a nonclinical position (OR, 2.48; 95% CI, 1.96-3.16), reporting work encroachment on private life (OR, 1.17; 95% CI, 1.10-1.25), feeling the need to constantly put on a brave face (OR, 1.82; 95% CI, 1.32-2.52), considering a career change (OR, 1.53; 95% CI, 1.22-1.92), and having experienced harassment (OR, 1.52; 95% CI, 1.22-1.88). Conclusions and Relevance: These findings suggest that the psychological burden on tenured university hospital faculty staff in France is considerable. Hospital administrators and health care authorities should urgently develop strategies for burden prevention and alleviation and for attraction of the next generation.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Epidemiology and challenges in the management of thyroid nodules.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with epidemiology and challenges in the management of thyroid nodules.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Surgical treatment.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French-speaking Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the surgical management of thyroid nodules.

Periostin- and podoplanin-positive cancer-associated fibroblast subtypes cooperate to shape the inflamed tumor microenvironment in aggressive pancreatic adenocarcinoma.

Cancer-associated fibroblasts (CAFs) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Previously we described four CAF subtypes with specific molecular and functional features. Here, we have refined our CAF subtype signatures using RNAseq and immunostaining with the goal of defining bioinformatically the phenotypic stromal and tumor epithelial states associated with CAF diversity. We used primary CAF cultures grown from patient PDAC tumors, human data sets (in-house and public, including single-cell analyses), genetically engineered mouse PDAC tissues, and patient-derived xenografts (PDX) grown in mice. We found that CAF subtype RNAseq signatures correlated with immunostaining. Tumors rich in periostin-positive CAFs were significantly associated with shorter overall survival of patients. Periostin-positive CAFs were characterized by high proliferation and protein synthesis rates and low α-smooth muscle actin expression and were found in peri-/pre-tumoral areas. They were associated with highly cellular tumors and with macrophage infiltrates. Podoplanin-positive CAFs were associated with immune-related signatures and recruitment of dendritic cells. Importantly, we showed that the combination of periostin-positive CAFs and podoplanin-positive CAFs was associated with specific tumor microenvironment features in terms of stromal abundance and immune cell infiltrates. Podoplanin-positive CAFs identified an inflammatory CAF (iCAF)-like subset, whereas periostin-positive CAFs were not correlated with the published myofibroblastic CAF (myCAF)/iCAF classification. Taken together, these results suggest that a periostin-positive CAF is an early, activated CAF, associated with aggressive tumors, whereas a podoplanin-positive CAF is associated with an immune-related phenotype. These two subpopulations cooperate to define specific tumor microenvironment and patient prognosis and are of putative interest for future therapeutic stratification of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Detection of Glycosylated Markers From Cancer Stem Cells With ColoSTEM Dx Kit for Earlier Prediction of Colon Cancer Aggressiveness.

Nowadays, colon cancer prognosis still difficult to predict, especially in the early stages. Recurrences remain elevated, even in the early stages after curative surgery. Carcidiag Biotechnologies has developed an immunohistochemistry (IHC) kit called ColoSTEM Dx, based on a MIX of biotinylated plant lectins that specifically detects colon cancer stem cells (CSCs) through glycan patterns that they specifically (over)express. A retrospective clinical study was carried out on tumor tissues from 208 non-chemotherapeutic-treated and 21 chemotherapeutic-treated patients with colon cancer, which were stained by IHC with the MIX. Clinical performances of the kit were determined, and prognostic and predictive values were evaluated. With 78.3% and 70.6% of diagnostic sensitivity and specificity respectively, our kit shows great clinical performances. Moreover, patient prognosis is significantly poorer when the MIX staining is "High" compared to "Low", especially at 5-years of overall survival and for early stages. The ColoSTEM Dx kit allows an earlier and a more precise determination of patients' outcome. Thus, it affords an innovating clinical tool for predicting tumor aggressiveness earlier and determining prognosis value regarding therapeutic response in colon cancer patients.

A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies.

Cancer stem cells play a crucial role in tumor initiation, metastasis, and resistance to treatment. Cellular heterogeneity and plasticity complicate the isolation of cancer stem cells. The impact of intra-tumor cellular heterogeneity using a label-free approach remains understudied in the context of treatment resistance. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three sorted cell subpopulations exhibits characteristics of cancer stem cells, including high tumorigenicity in vivo and a higher frequency of tumor-initiating cells compared to the other subpopulations. Due to its chemoresistance, two- and three-dimensional in vitro chemosensitivity assays highlight the therapeutic relevance of this cancer stem cell subpopulation. Thus, our results reveal the major implication of intra-tumor cellular heterogeneity, including cancer stem cells in treatment resistance, thanks to our label-free cell sorting approach. This approach enables-by breaking down the tumor-the study the individualized response of each sorted tumor cell subpopulation and to identify chemoresistance, thus offering new perspectives for personalized therapy.

The effect of metformin on the survival of colorectal cancer patients with type 2 diabetes mellitus.

Evidence from previous studies suggests a protective effect of metformin in patients with colorectal cancer (CRC). The aim of this study was to examine the associations between metformin use and overall survival (OS) and disease-free survival (DFS) in CRC patients with type 2 diabetes mellitus (DM). We retrospectively included patients who underwent surgery for CRC at Limoges' University Hospital between 2005 and 2019 and diagnosed with type 2 DM. Data on the characteristics of patients, CRC, comorbidities and drug exposure were collected from the electronic medical records. The exposure was the use of metformin and the outcomes were OS and DFS. We identified 290 CRC patients with type 2 DM. A total of 144 (49.7%) of them were treated with metformin. Metformin users were significantly younger, with higher body mass index and less diabetes-related complications compared to non-users. The 2-year OS was significantly higher in metformin users than in non-users (86.9 ± 2.9% vs. 71.0 ± 4.0%, p = 0.001). In multivariate analysis, metformin use was associated with better OS (adjusted hazard ratios [aHR] = 0.45 95% confidence interval [95% CI]: 0.21-0.96) and better DFS (aHR = 0.31; 95% CI: 0.18-0.54). In conclusion, the use of metformin may improve OS and DFS in CRC patients with type 2 DM.

Impact of a procalcitonin-based algorithm on the quality of management of patients with uncomplicated adhesion-related small bowel obstruction assessed by a textbook outcome: a multicenter cluster-randomized open-label controlled trial.

BACKGROUND: Acute adhesion-related small bowel obstruction (ASBO) is a common digestive emergency, accounting for 1 to 3% of all digestive emergencies. The efficacy of conservative management in this setting is a subject of debate, as it may delay the decision to perform surgery and increase the frequency of bowel resection (e.g., in the presence of bowel necrosis) or, in contrast, prompt an excessive number of unnecessary laparotomies. Thus, the decision to perform surgery is difficult. We propose that the introduction of the procalcitonin (PCT)-based algorithm improves the quality of the management of patients with ASBO by aiding the decision of whether or not to perform surgery. METHODS: This is a 1:1 cluster-randomized clinical trial (use of algorithm: no algorithm) using an independent computer to ensure that investigators cannot interfere with the randomization. Each cluster will correspond to one investigating center. All patients in a center will be managed in the same way. Before randomization, each principal investigator will provide a commitment to participate in the study to avoid the risk of "empty clusters". The patients included will constitute two parallel arms (use of algorithm versus no algorithm), with no expected crossover between arms. The inclusion criteria are being an adult with uncomplicated acute ASBO (i.e., absence of fever, abdominal pain and distension, nausea and/or vomiting, and the absence of gas and/or stool, in conjunction with a contrast-enhanced CT scan, for patients with previous abdominal surgery) who is able to express consent with a signed written informed consent form. Patients with complicated acute ASBO (strangulation or peritonitis) will be excluded. DISCUSSION: There is an ongoing debate on the management of uncomplicated ASBO. The main points are to avoid a surgery if it is unnecessary and to avoid delayed surgery if it is necessary. Currently, there are no robust criteria to objectively determine the failure of non-surgical treatment or to establish the indications for surgery in acute ASBO. Our team proposes the use of procalcitonin (PCT) to help distinguish patients for whom conservative management is likely to be successful from those for whom surgical management is required. The results from a randomized control trial could help in the selection of patients through clear inclusion and exclusion criteria and simplify or clarify the management algorithm. In conclusion, PCT may be useful in evaluating the proper strategy for ASBO. Trial registration The trial is registered at clinical trials under the reference: NCT03905239.