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2.
Curr Probl Surg ; 61(9): 101546, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39168531
3.
Colorectal Dis ; 26(7): 1437-1446, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38886887

RESUMO

AIM: The aim of this work was to investigate the association between early postoperative anastomotic leakage or pelvic abscess (AL/PA) and symptomatic anastomotic stenosis (SAS) in patients after surgery for left colonic diverticulitis. METHOD: This is a retrospective study based on a national cohort of diverticulitis surgery patients carried out by the Association Française de Chirurgie. The assessment was performed using path analyses. The database included 7053 patients operated on for colonic diverticulitis, with surgery performed electively or in an emergency, by open access or laparoscopically. Patients were excluded from the study analysis where there was (i) right-sided diverticulitis (the initial database included all consecutive patients operated on for colonic diverticulitis), (ii) no anastomosis was performed during the first procedure or (iii) missing information about stenosis, postoperative abscess or anastomotic leakage. RESULTS: Of the 4441 patients who were included in the final analysis, AL/PA occurred in 327 (4.6%) and SAS occurred in 82 (1.8%). AL/PA was a significant independent factor associated with a risk for occurrence of SAS (OR = 3.41, 95% CI = 1.75-6.66), as was the case for diverting stoma for ≥100 days (OR = 2.77, 95% CI = 1.32-5.82), while central vessel ligation proximal to the inferior mesenteric artery was associated with a reduced risk (OR = 0.41; 95% CI = 0.19-0.88). Diverting stoma created for <100 days or ≥100 days was also a factor associated with a risk for AL/PA (OR = 3.08, 95% CI = 2-4.75 and OR = 12.95, 95% CI = 9.11-18.50). Interestingly, no significant association between radiological drainage or surgical management of AL/PA and SAS could be highlighted. CONCLUSION: AL/PA was an independent factor associated with the risk for SAS. The treatment of AL/PA was not associated with the occurrence of anastomotic stenosis. Diverting stoma was associated with an increased risk of both AL/PA and SAS, especially if it was left for ≥100 days. Physicians must be aware of this information in order to decide on the best course of action when creating a stoma during elective or emergency surgery.


Assuntos
Anastomose Cirúrgica , Fístula Anastomótica , Doença Diverticular do Colo , Humanos , Estudos Retrospectivos , Masculino , Feminino , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Pessoa de Meia-Idade , Idoso , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Doença Diverticular do Colo/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Reto/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Colo/cirurgia , Fatores de Risco , França/epidemiologia , Abscesso/etiologia , Abscesso/cirurgia
4.
Psychiatry Res ; 337: 115946, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38703562

RESUMO

Brain-derived neurotrophic factor (BDNF) is an important regulatory protein in the pathophysiology of psychiatric disorders. Several studies have reported the relationship between peripheral BDNF concentrations and the use of psychoactive drugs. However, the results remain controversial. This study aimed to evaluate the effects of psychoactive drugs on BDNF concentrations and to explore the association between changes in BDNF concentrations and improvements in clinical scores. A systematic review and meta-analysis were conducted. Six electronic databases, including PubMed, Scopus, Medline, Web of Science, Google Scholar and Science Direct, were searched. Changes in BDNF concentrations were compared before and after psychoactive treatment, using the standardized mean difference (SMD) and 95 % confidence interval (95 % CI). Twenty-three studies were included. A significant increase in serum BDNF concentrations was observed after treatment with antipsychotics (SMD=0.43; 95 %CI: 0.26, 0.60) and antidepressants (SMD=0.49; 95 %CI: 0.23, 0.74). However, the plasma BDNF concentration was not affected by antidepressant and antipsychotic medication. Although an improvement in clinical scores was observed after treatment, no significant association was observed between changes in BDNF concentrations and the changes in the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAM-D) scores. In conclusion, antidepressants and antipsychotics increase serum BDNF concentrations.


Assuntos
Antidepressivos , Antipsicóticos , Fator Neurotrófico Derivado do Encéfalo , Humanos , Fator Neurotrófico Derivado do Encéfalo/sangue , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia , Antipsicóticos/uso terapêutico , Antipsicóticos/farmacologia
5.
Cancer Rep (Hoboken) ; 7(2): e1993, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38351532

RESUMO

BACKGROUND: Prophylactic central neck dissection (pCND) remains controversial during the initial surgery for preoperative and intraoperative node-negative (cN0) papillary thyroid carcinoma (PTC). METHODS: Patients undergoing thyroidectomy with or without pCND (Nx) for PTC in nine French surgical departments, registered in the EUROCRINE® national data in France between January 2015 and June 2021, were included in a cohort study. Demographic and clinicopathological characteristics, complications, and recurrence rates were compared using multivariate regression analysis. RESULTS: A total of 1905 patients with cN0 PTC were enrolled, including 1534 who had undergone pCND and 371 who hadn't (Nx). Of these, 1546 (81.2%) were female, and the median age was 49 years (range: 15-89 years). Patients who had undergone pCND were more likely to have multifocal tumors (n = 524 [34.2%] vs. n = 68 [18.3%], p < .001) and larger tumors (15.3 vs. 10.2 mm, p = .01) than patients with Nx. Of the patients with pCND, 553 (36%) had positive central LN (N1a), with a median of 1 N1 (IQR 0-5). pCND was associated with a higher temporary hypocalcemia rate (n = 25 [8%] vs. n = 15 [4%], p < .001). The rates of permanent hypocalcemia and temporary and permanent recurrent laryngeal nerve (RLN) palsy were not significantly different between the two groups (p > .2). After adjusting for covariates (age, sex, multifocality, and pathological T stage) in a multivariable Cox PH model, the performance of lymph node dissection (pCND vs. no-pCND) was not associated with PTC recurrence (p = .2). CONCLUSION: pCND in PTC does not reduce recurrence and is associated with a two-fold increase in the incidence of transient hypoparathyroidism. These data should be considered while issuing further guidelines regarding the treatment of patients with cN0 PTC.


Assuntos
Carcinoma Papilar , Hipocalcemia , Neoplasias da Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Esvaziamento Cervical/efeitos adversos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos de Coortes , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Carcinoma Papilar/cirurgia
6.
Ann Surg ; 279(2): 340-345, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37389888

RESUMO

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.


Assuntos
Hiperparatireoidismo Primário , Neoplasia Endócrina Múltipla Tipo 1 , Humanos , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/complicações , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Glândulas Paratireoides , Paratireoidectomia , Recidiva
7.
Biomed Pharmacother ; 170: 115950, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039757

RESUMO

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.


Assuntos
Ansiolíticos , Neoplasias Colorretais , Humanos , Benzodiazepinas/efeitos adversos , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Hipnóticos e Sedativos
8.
Int J Colorectal Dis ; 38(1): 276, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38040936

RESUMO

OBJECTIVE: To analyze the surgical management of sigmoid diverticular disease (SDD) before, during, and after the first containment rules (CR) for the first wave of COVID-19. METHODS: From the French Surgical Association multicenter series, this study included all patients operated on between January 2018 and September 2021. Three groups were compared: A (before CR period: 01/01/18-03/16/20), B (CR period: 03/17/20-05/03/20), and C (post CR period: 05/04/20-09/30/21). RESULTS: A total of 1965 patients (A n = 1517, B n = 52, C n = 396) were included. The A group had significantly more previous SDD compared to the two other groups (p = 0.007), especially complicated (p = 0.0004). The rate of peritonitis was significantly higher in the B (46.1%) and C (38.4%) groups compared to the A group (31.7%) (p = 0.034 and p = 0.014). As regards surgical treatment, Hartmann's procedure was more often performed in the B group (44.2%, vs A 25.5% and C 26.8%, p = 0.01). Mortality at 90 days was significantly higher in the B group (9.6%, vs A 4% and C 6.3%, p = 0.034). This difference was also significant between the A and B groups (p = 0.048), as well as between the A and C groups (p = 0.05). There was no significant difference between the three groups in terms of postoperative morbidity. CONCLUSION: This study shows that the management of SDD was impacted by COVID-19 at CR, but also after and until September 2021, both on the initial clinical presentation and on postoperative mortality.


Assuntos
COVID-19 , Doença Diverticular do Colo , Divertículo , Humanos , Anastomose Cirúrgica/métodos , Colo Sigmoide/cirurgia , Colostomia/métodos , Doença Diverticular do Colo/cirurgia , Doença Diverticular do Colo/complicações , Divertículo/complicações , Complicações Pós-Operatórias , Reto/cirurgia , Estudos Retrospectivos
9.
Cancers (Basel) ; 15(14)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37509386

RESUMO

(1) Background: Metformin, an anti-diabetic drug, seems to protect against aggressive acquisition in colorectal cancers (CRCs). However, its mechanisms are still really unknown, raising questions about the possibility of its positive impact on non-diabetic patients with CRC. (2) Methods: An in vitro study based on human colon cancer cell lines and an ex vivo study with different colon cancer stages with proteomic and transcriptomic analyses were initiated. (3) Results: Metformin seems to protect from colon cancer invasive acquisition, irrespective of glucose concentration. (4) Conclusions: Metformin could be used as an adjuvant treatment to surgery for both diabetic and non-diabetic patients in order to prevent the acquisition of aggressiveness and, ultimately, recurrences.

10.
J Visc Surg ; 160(3S): S119-S126, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37211444

RESUMO

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.


Assuntos
Bócio Nodular , Tireoidectomia , Humanos , Tireoidectomia/métodos , Excisão de Linfonodo
11.
Surgery ; 174(1): 46-51, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37156647

RESUMO

BACKGROUND: Anastomosis leak is one of the significant postoperative complications after colorectal surgery. The aim of this systematic review was to synthesize the evidence relative to the preoperative assessment of the colon and rectum blood supply and to investigate its role in predicting anastomosis leak. METHOD: This systematic review was conducted according to the recommendations of the Cochrane Handbook for Reviews of Interventions and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Embase, and the Cochrane Library were searched to identify eligible studies. The main outcome variable was the preoperative assessment of patterns of blood supply to the colon and the impact of these patterns on anastomosis leak. The quality of bias control in the studies was assessed using the Newcastle-Ottawa Scale. Due to the heterogeneous nature of the included studies, no meta-analysis was conducted. RESULTS: Fourteen studies were included. The study covered a period from 1978 to 2021. A significant degree of variation in the arterial and/or venous supply of the colon and rectum might influence anastomosis leak rates. Calcification in great blood vessels can be assessed with a preoperative computed tomography scan, which may predict anastomosis leak rates. This is supported by many experimental studies that showed increased rates of anastomosis leak after preoperative ischemia, but the extent of this impact is not well established. CONCLUSION: Preoperative assessment of blood supply to the colon and rectum might help in planning the surgical intervention to reduce anastomosis leak rates. Calcium scoring of major arteries might predict anastomosis leak and thus play a crucial role in intraoperative decision-making.


Assuntos
Fístula Anastomótica , Colo , Humanos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Colo/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Reto/cirurgia
12.
Colorectal Dis ; 25(7): 1433-1445, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37254657

RESUMO

AIM: The long-term urological sequelae after iatrogenic ureteral injury (IUI) during colorectal surgery are not clearly known. The aims of this work were to report the incidence of IUI and to analyse the long-term consequences of urological late complications and their impact on oncological results of IUI occurring during colorectal surgery through a French multicentric experience (GRECCAR group). METHOD: All the patients who presented with IUI during colorectal surgery between 2010 and 2019 were retrospectively included. Patients with ureteral involvement needing en bloc resection, delayed ureteral stricture or noncolorectal surgery were not considered. RESULTS: A total of 202 patients (93 men, mean age 63 ± 14 years) were identified in 29 centres, corresponding to 0.32% of colorectal surgeries (n = 63 562). Index colorectal surgery was mainly oncological (n = 130, 64%). IUI was diagnosed postoperatively in 112 patients (55%) after a mean delay of 11 ± 9 days. Intraoperative diagnosis of IUI was significantly associated with shorter length of stay (21 ± 22 days vs. 34 ± 22 days, p < 0.0001), lower rates of postoperative hydronephrosis (2% vs. 10%, p = 0.04), anastomotic complication (7% vs. 22.5%, p = 0.002) and thromboembolic event (0% vs. 6%, p = 0.02) than postoperative diagnosis of IUI. Delayed chemotherapy because of IUI was reported in 27% of patients. At the end of the follow-up [3 ± 2.6 years (1 month-13 years)], 72 patients presented with urological sequalae (36%). Six patients (3%) required a nephrectomy. CONCLUSION: IUI during colorectal surgery has few consequences for the patients if recognized early. Long-term urological sequelae can occur in a third of patients. IUI may affect oncological outcomes in colorectal surgery by delaying adjuvant chemotherapy, especially when the ureteral injury is not diagnosed peroperatively.


Assuntos
Traumatismos Abdominais , Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Ureter , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Cirurgia Colorretal/efeitos adversos , Ureter/cirurgia , Ureter/lesões , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Traumatismos Abdominais/etiologia , Doença Iatrogênica/epidemiologia
13.
Ann Endocrinol (Paris) ; 83(6): 415-422, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36309207

RESUMO

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.


Assuntos
Endocrinologia , Medicina Nuclear , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia , Cintilografia , Neoplasias da Glândula Tireoide/patologia
14.
J Clin Med ; 11(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36078996

RESUMO

Background: Enhanced or accelerating recovery programs have significantly reduced hospital length stay after elective colorectal interventions. Our work aims at reporting an initial experience with ambulatory laparoscopic colectomy (ALC) to assess the criteria of discharge and outcomes. Methods: Between 2006 and 2016, data regarding patients having benefited from elective laparoscopic colorectal resections in two main centres in the United Kingdom have been analysed. Both benign and malignant pathologies were included. A standardised enhanced recovery program was performed for each patient, except epidural analgesia was replaced with single shot spinal infiltration. Patients were followed up through a telephone call system by a nurse. Short-term clinical outcomes were analysed. Results: A total of 833 patients were included and 51 (6.1%) were discharged within 24 h following surgery. Of these, 4 out of 51 (7.8%) patients came back hospital within 30 days of discharge; 2 (3.9%) required reoperation (Small bowel obstruction and wound abscess drainage). Conclusions: This study highlights that a 24-h discharge following elective laparoscopic colorectal interventions seems safe and feasible in selected patients. Although challenging to achieve, a standardised approach to laparoscopic surgery in combination with strict adherence to an enhanced recovery protocol are the fundamental elements of this path.

15.
Front Oncol ; 12: 918702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936672

RESUMO

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.

16.
Cells ; 11(15)2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35892561

RESUMO

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.


Assuntos
Transformação Celular Neoplásica , Células-Tronco Neoplásicas , Linhagem Celular Tumoral , Movimento Celular , Separação Celular , Transformação Celular Neoplásica/metabolismo , Humanos , Células-Tronco Neoplásicas/patologia
17.
Sci Rep ; 12(1): 12374, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35859114

RESUMO

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.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Metformina , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Estudos Retrospectivos
18.
Eur J Cancer ; 166: 100-111, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35279470

RESUMO

BACKGROUND: Diabetes mellitus (DM) has been associated with increased colorectal cancer (CRC) risk and worse prognosis in metastatic CRC patients. In this large, pooled analysis of non-metastatic colon cancer (CC) patients, we investigated the impact of DM and metformin treatment on recurrence and survival. PATIENTS AND METHODS: A patient-level pooled analysis from three randomised adjuvant trials was performed. All patients had resection with curative intent of stage II or III CC and were treated with standard adjuvant fluoropyrimidine and oxaliplatin (±cetuximab). We investigated the impact of DM and metformin treatment on time to recurrence (TTR) and overall survival (OS). RESULTS: Of 5922 CC patients who had a median follow-up of 6.8 years, 621 patients (10.5%) had DM at CC diagnosis. Of those with DM, 327 patients (52.7%) were defined as metformin users and 294 patients (47.3%) as non-metformin users. CC patients with DM had a significantly shorter TTR (adjHR: 1.21; 95% CI, 1.03-1.42; p = 0.017) and OS (adjHR: 1.29; 95% CI, 1.09-1.52; p = 0.003) compared to non-diabetic CC patients. Diabetic CC patients not receiving metformin had a significantly worse TTR (adjHR: 1.28; 95% CI, 1.02-1.60; p = 0.032) and OS (adjHR: 1.41; 95% CI, 1.13-1.77; p = 0.003) as compared to non-diabetic patients. These worse outcomes were not significant in metformin users (TTR: adjHR: 1.16; 95% CI, 0.94-1.43; p = 0.168; OS: adjHR: 1.19; 95% CI, 0.95-1.48, p = 0.127). CONCLUSIONS: CC patients with DM had not only a significantly worse survival but also TTR. Furthermore, our data suggest that metformin may attenuate the detrimental effect of DM on CC patient outcomes.


Assuntos
Neoplasias do Colo , Diabetes Mellitus , Metformina , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Oxaliplatina/uso terapêutico
19.
World J Surg ; 46(4): 784-790, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35128570

RESUMO

BACKGROUND: Gastric pneumatosis (GP) is a rare radiologic finding with an unpredictable prognosis. The aim of this study was to identify mortality risk factors from patients presenting with GP on computed tomography (CT), and to develop a model which would allow us to predict which patients would benefit most from operative management. METHODS: Between 2010 and 2020, all CT-scan reports in four tertiary centers were searched for the following terms: "gastric pneumatosis," "intramural gastric air" or "emphysematous gastritis." The retrieved CT scans were reviewed by a senior surgeon and a senior radiologist. Relevant clinical and laboratory data for these patients were extracted from the institutions' medical records. RESULTS: Among 58 patients with GP, portal venous gas and bowel ischemia were present on CT scan in 52 (90%) and 17 patients (29%), respectively. The 30-day mortality rate was 31%. Univariate analysis identified the following variables as predictive of mortality at the time of the diagnosis of GP: abdominal guarding, hemodynamic instability, arterial lactate level >2 mmol/l, and the absence of gastric dilatation. Multivariable analysis identified the following variables as independent predictors of mortality: arterial lactate level (OR: 1.39, 95% CI: 1.07-1.79) and the absence of gastric dilatation (OR: 0.07, 95% CI: 0.01-0.79). None of the patients presenting with a baseline lactate rate<2 mmol/l died within 30 days following diagnosis, and no more than 17 patients out of 58 had bowel ischemia (29%). CONCLUSIONS: GP could be managed non-operatively, even in the presence of portal venous gas. However, patients with arterial lactate level>2 mmol/l, or the absence of gastric dilation should be surgically explored due to a non-negligible risk of mortality.


Assuntos
Dilatação Gástrica , Isquemia Mesentérica , Pneumatose Cistoide Intestinal , Humanos , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Isquemia/cirurgia , Ácido Láctico , Pneumatose Cistoide Intestinal/diagnóstico por imagem , Pneumatose Cistoide Intestinal/terapia , Veia Porta/diagnóstico por imagem , Estudos Retrospectivos
20.
Int J Mol Sci ; 23(4)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35216426

RESUMO

As is the case with most eucaryotic cells, cancer cells are able to secrete extracellular vesicles (EVs) as a communication means towards their environment and surrounding cells. EVs are represented by microvesicles and smaller vesicles called exosomes, which are known for their involvement in cancer aggressiveness. The release of such EVs requires the intervention of trafficking-associated proteins, mostly represented by the RAB-GTPases family. In particular, RAB27A is known for its role in addressing EVs-to-be secreted towards the the plasma membrane. In this study, shRNAs targeting RAB27A were used in colorectal (CRC) and glioblastoma (GB) cell lines in order to alter EVs secretion. To study and monitor EVs secretion in cell lines' supernatants, nanoparticle tracking analysis (NTA) was used through the NanoSight NS300 device. Since it appeared that NanoSight failed to detect the decrease in the EVs secretion, we performed another approach to drop EVs secretion (RAB27A-siRNA, indomethacin, Nexihnib20). Similar results were obtained i.e., no variation in EVs concentration. Conversely, NTA allowed us to monitor EVs up-secretion following rotenone treatment or hypoxia conditions. Therefore, our data seemed to point out the insufficiency of using only this technique for the assessment of EVs secretion decrease.


Assuntos
Biotecnologia/métodos , Vesículas Extracelulares/metabolismo , Nanopartículas/metabolismo , Linhagem Celular Tumoral , Micropartículas Derivadas de Células/metabolismo , Exossomos/metabolismo , Células HCT116 , Humanos , Neoplasias/metabolismo , Transporte Proteico/fisiologia
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