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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Acta Chir Belg ; 122(6): 420-423, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33502964

RESUMO

BACKGROUND: Sclerosing Encapsulating peritonitis (SEP) is a rare chronic fibro-inflammatory disease of the peritoneum. The aetiology can be either primary or secondary. The knowledge around this topic is poor. CASE PRESENTATION: Based on the report of a 64-year-old man suffering from intestinal obstruction and its management with a final diagnosis of primary SEP, herein we review the literature concerning this specific entity of primary SEP and its challenge in both diagnosis and treatment. CONCLUSION: whereas SEP is a rare entity, imagery is helpful to make the diagnosis.


Assuntos
Obstrução Intestinal , Peritonite , Masculino , Humanos , Pessoa de Meia-Idade , Peritonite/diagnóstico , Peritonite/etiologia , Peritonite/terapia , Peritônio , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Doença Crônica
8.
J Cell Mol Med ; 25(1): 47-60, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33325631

RESUMO

Colorectal cancer (CRC) is the third most common cancer worldwide. Even if 5-fluorouracil (5-FU) is used as the first-line chemotherapeutic drug, responsiveness is only 20-30%. Acquired resistance to 5-FU contributes to both poor patient prognosis and relapse, emphasizing the need to identify biomarkers. Sortilin, a vacuolar protein sorting 10 protein (Vps10p), implicated in protein trafficking, is over expressed in CRC cell lines cultured 72 hours in presence of 5-FU. This overexpression was also observed in 5-FU-resistant cells derived from these cell lines as well as in CRC primary cultures (or patients derived cell lines). A significantly higher expression of sortilin was observed in vivo, in 5-FU-treated tumours engrafted in Nude mice, as compared with non-treated tumour. A study of transcriptional regulation allowed identifying a decrease in ATF3 expression, as an explanation of sortilin overexpression following 5-FU treatment. In silico analysis revealed SORT1 expression correlation with poor prognosis. Moreover, sortilin expression was found to be positively correlated with CRC tumour grades. Collectively, our findings identify sortilin as a potential biomarker of 5-FU resistance associated with poor clinical outcomes and aggressiveness in CRC. As a new prognostic factor, sortilin expression could be used to fight against CRC.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Proteínas Adaptadoras de Transporte Vesicular/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Gradação de Tumores , Prognóstico , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Surg Endosc ; 35(2): 702-709, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32060746

RESUMO

BACKGROUND: Biological acellular porcine dermis mesh, such as Permacol™, has been used since 2009 to treat abdominal incisional hernias in a septic context. This study investigated the risk factors for incisional hernia recurrence after biological mesh augmentation. RESULTS: Over a period of 6 years from February 2009 to February 2015, 68 patients underwent surgery. The mesh was placed intraperitoneally with closure of the anterior fascia in 27 cases (39.7%). The biological mesh was placed in the retromuscular pre-fascial plane in 1 case (1.5%) and pre-aponeurotic plane in 1 case (1.5%). Closure of the anterior fascia was not achieved in 39 cases, including 20 cases in which the mesh was placed intraperitoneally (intraperitoneal bridging group, 29.4%) and 19 cases in which the mesh was placed between the edges of the fascia (inlay bridging group, 27.9%). There were 37 cases of postoperative surgical site infections (54.4%), and Clavien-Dindo morbidity staging indicated stage I-II and III-IV complications in 19.1% and 44.1% of the cases, respectively. The recurrence rate was 61.8%, and the mortality rate was 0%. The rate of recurrence was significantly lower in the «fascia approximated¼ group (37%), p = 0.001). Univariate analyses of risk factors for procedural failure indicated an increased risk of recurrence in cases of postoperative surgical site infections, complications of Clavien-Dindo grade III or higher, an absent fascial closure in front of the mesh (OR = 8.69), an operating time longer than 180 min, and a VHWG score higher than 2. After logistic regression, the risk factors for recurrence were postoperative infections (OR = 6.2), placement of bridged biological mesh (OR = 22.3), and postoperative morbidity grade III or higher (OR = 16.7). CONCLUSIONS: Patients with postoperative surgical site infections are at an increased risk for recurrence, and bridged mesh placements lack efficacy. Overall, this study challenges the purported advantage of biologics in treating incisional hernia repairs.


Assuntos
Hérnia Ventral/cirurgia , Herniorrafia/métodos , Telas Cirúrgicas/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suínos
10.
World J Surg ; 45(5): 1537-1547, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33543333

RESUMO

IMPORTANCE: Rectal cancers occupy the eighth position worldwide for new cases and deaths for both men and women. These cancers have a high tendency to form metastases in the mesorectum but also in the lateral lymph nodes. The therapeutic approach for the involved lateral lymph nodes remains controversial. OBJECTIVE: We performed a systematic review and meta-analysis to assess the prevalence of metastatic lateral lymph nodes in patients with lateral lymph node dissection (LLND) for rectal cancer, which seems to be a fundamental and necessary criterion to discuss any possible indications for LLND. METHODS: Data sources-study selection-data extraction and synthesis-main outcome and measures. We searched MEDLINE, EMBASE and COCHRANE from November 1, 2018, to November 19, 2018, for studies reporting the presence of metastatic lateral lymph nodes (iliac, obturator and middle sacral nodes) among patients undergoing rectal surgery with LLND. Pooled prevalence values were obtained by random effects models, and the robustness was tested by leave-one-out sensitivity analyses. Heterogeneity was assessed using the Q-test, quantified based on the I2 value and explored by subgroup analyses. RESULTS: Our final analysis included 31 studies from Asian countries, comprising 7599 patients. The pooled prevalence of metastatic lateral lymph nodes was 17.3% (95% CI: 14.6-20.5). The inter-study variability (heterogeneity) was high (I2 = 89%). The pooled prevalence was, however, robust and varied between 16.6% and 17.9% according to leave-one-out sensitivity analysis. The pooled prevalence of metastatic lymph nodes was not significantly different when pooling only studies including patients who received neoadjuvant treatment or those without neoadjuvant treatment (p = 0.44). Meta-regression showed that the pooled prevalence was associated with the sample size of studies (p < 0.05), as the prevalence decreased when the sample size increased. CONCLUSION: The pooled prevalence of metastatic lateral lymph nodes was 17.3% among patients who underwent rectal surgery with LLND in Asian countries. Further studies are necessary to determine whether this finding could impact the therapeutic strategy (total mesorectal excision with LLND versus total mesorectal excision with neoadjuvant radiochemotherapy).


Assuntos
Recidiva Local de Neoplasia , Neoplasias Retais , Ásia/epidemiologia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Masculino , Prevalência , Neoplasias Retais/cirurgia
11.
BMC Surg ; 21(1): 197, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865363

RESUMO

BACKGROUND: Surgical wound infection contributes to prolonged recovery time after pilonidal sinus excision. As a standard procedure after surgery, we recommend our patients to perform water irrigations in the intergluteal cleft 4 to 6 times a day during the post-operative period. Our hypothesis is that this should reduce healing time and complication rates. The aim of this study was to measure the importance of sacro coccygeal hygiene in the management of pilonidal sinus disease. METHODS: We retrospectively collected data after surgical management of pilonidal sinus (sinusectomy procedures) in our division over a 10-year period. Patients were divided into three groups according to their local hygiene during postoperative follow-up and scored one (G1: good hygiene) to three (G3: poor hygiene). Primary outcome was complication rates. Secondary endpoints were, healing time, follow-up, time off work, and recurrence rate. RESULTS: In G1 (N = 112), complication rate was 3.6%. In G2 (N = 109), it was 5.5%, whereas in G3 (N = 71), it reached 7.03%. However, there were no statistically significant differences between hygiene groups regarding complication rates in both univariate and multivariable analysis. Regarding secondary outcomes, there were significant differences between hygiene groups concerning median follow-up (p = 0.0001) and median time off work (p = 0.0127). CONCLUSION: Good hygiene of wound is essential for optimal, rapid healing without complications. The importance of this report is to show that thanks to our hygiene follow-up strategy with frequent perineal irrigations and regular follow-up checks, patients with at a first glance "unclean local conditions", reached similar complications, median healing time and recurrences rates to patients with medium and good wound hygiene level.


Assuntos
Higiene , Seio Pilonidal/cirurgia , Região Sacrococcígea , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Recidiva , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do Tratamento , Cicatrização , Adulto Jovem
12.
Int J Mol Sci ; 22(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33918012

RESUMO

Despite therapeutic advances, colorectal cancer (CRC) is still one of the deadliest cancers, partly due to local recurrence and metastatic disease. Tumour cells that spread by gaining access to peripheral blood are called circulating tumour cells (CTCs). These may be present before there are any clinical signs, but can be detected within blood samples. CTCs from patients with CRC may be isolated in a laboratory for characterization and multiple analyses. In this review, we focus on the prognostic potential of CTCs detection, by evaluating the reported progress and applications of such analyses. Our search found 77 relevant studies that reported CTC detection in CRC. Both cell count and features were reported as promising prognosis biomarkers. Since CTCs are rare and can lose their differentiation, new tools are being developed to improve detection. CTCs may have potential as prognostic biomarkers for CRC in terms of survival prediction, anticipating chemotherapy resistance, and surgical planning. CTCs are not yet used in clinical practice, and further investigations are required in order to better frame their practical value.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Células Neoplásicas Circulantes , Contagem de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Humanos , Prognóstico
13.
Cancer Sci ; 111(9): 3142-3154, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32536012

RESUMO

Colorectal cancer (CRC) is a public health problem. It is the third most common cancer in the world, with nearly 1.8 million new cases diagnosed in 2018. The only curative treatment is surgery, especially for early tumor stages. When there is locoregional or distant invasion, chemotherapy can be introduced, in particular 5-fluorouracil (5-FU). However, the disease can become tolerant to these pharmaceutical treatments: resistance emerges, leading to early tumor recurrence. Different mechanisms can explain this 5-FU resistance. Some are disease-specific, whereas others, such as drug efflux, are evolutionarily conserved. These mechanisms are numerous and complex and can occur simultaneously in cells exposed to 5-FU. In this review, we construct a global outline of different mechanisms from disruption of 5-FU-metabolic enzymes and classic cellular processes (apoptosis, autophagy, glucose metabolism, oxidative stress, respiration, and cell cycle perturbation) to drug transporters and epithelial-mesenchymal transition induction. Particular interest is directed to tumor microenvironment function as well as epigenetic alterations and miRNA dysregulation, which are the more promising processes that will be the subject of much research in the future.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Transdução de Sinais/efeitos dos fármacos , Antimetabólitos Antineoplásicos/metabolismo , Biomarcadores , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Metabolismo Energético/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Fluoruracila/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Redes e Vias Metabólicas , Estresse Oxidativo/efeitos dos fármacos , Timidilato Sintase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
14.
Ann Pharmacother ; 54(8): 804-814, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32054312

RESUMO

Objective: Commonly used drugs may be dangerous in case of extravasation. The lack of information from health care teams can lead to delays in both diagnosis and treatments. This review aims at alerting health care professionals about drugs and risk factors for extravasation and outlines recommendations for the diagnosis and treatment of extravasation. Data Source: A literature search of MEDLINE/PubMed, Scopus, the Cochrane Library, and Google Scholar was performed from 2000 to December 2019 using the following terms: extravasation, central venous line, peripheral venous line, irritant, and vesicant. Study Selection and Data Extraction: Overall, 140 articles dealing with drug extravasation were considered potentially relevant. Each article was critically appraised independently by 2 authors, leading to the inclusion of 80 relevant studies, guidelines, and reviews. Articles discussing incidents of extravasation in the neonatal and pediatric population of patients were excluded. Data Synthesis: Training of health care teams and writing care protocols are important for an optimal management of extravasations. A prompt consultation should be achieved by a specialist surgeon. The surgical procedure, if necessary, will consist of wound debridement followed by an abundant lavage. Relevance to Patient Care and Clinical Practice: This review discusses the management of drug extravasations according to their mechanism(s) of toxicity on tissues. It highlights the importance of a close monitoring of patients and the training of health care teams likely to face this type of adverse event. Conclusions: Extravasations still contribute to significant morbidity and mortality. A good knowledge of risk factors and the implementation of easily and quickly accessible standardized care protocols are 2 key elements in both prevention and treatment of extravasations.


Assuntos
Extravasamento de Materiais Terapêuticos e Diagnósticos , Vasoconstritores , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/terapia , Humanos , Concentração Osmolar , Fatores de Risco , Irrigação Terapêutica , Vasoconstritores/administração & dosagem , Vasoconstritores/efeitos adversos , Vasoconstritores/química
15.
Int J Colorectal Dis ; 35(7): 1183-1192, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32458399

RESUMO

PURPOSE: Treatment of lateral lymph node metastasis in rectal cancer is still under debate. While these nodes are routinely resected by Japanese teams, neoadjuvant radiochemotherapy alone is performed in Western countries. We aimed to systematically report the current literature assessing the overall and disease-free survivals of patients with rectal cancer treated with total mesorectal resection (TME) with or without lateral lymph node dissection (LLND). METHODS: MEDLINE/Pubmed, Embase, Cochrane, and Web of Science were searched from database implementation until 19 January 2019. Studies reporting overall survival or recurrence-free survival in patients with LLND for rectal cancer were included. We excluded studies including patients with recurrent rectal cancer, multivisceral resection, and/or without control group (patients with rectal surgery without LLND). RESULTS: Eleven studies were included, accounting for a total of 4159 patients. Overall survival ranged between 55.6 and 92.6% for TME with LLND versus 49.2 and 90.2% for TME alone, with one study reporting statistically significant benefit of LLND. Recurrence-free survival ranged between 58.3 and 74.1% for TME with LLND versus 39.5 and 76.5% for TME alone. Two studies showed statistically significant differences between the two strategies, one randomized controlled trial showed improved recurrence-free survival in TME alone group (74.5% versus 74.1% with LLND at 5 years) and one observational retrospective study reported increased recurrence-free survival with more extensive resection (65.4% versus 39.5% without LLND, at 5 years). CONCLUSION: Benefits of LLND are not clear and further randomized controlled trials should be performed to determine which strategy would allow improving survival in rectal cancer patients. TRIAL REGISTRATION: The study protocol was registered in PROSPERO prior to study screening (CRD42019123181) and published in September 2019.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Retais , Humanos , Excisão de Linfonodo , Linfonodos , Neoplasias Retais/cirurgia , Estudos Retrospectivos
16.
Dig Endosc ; 32(5): 816-822, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32022334

RESUMO

Several recent studies have described the feasibility, efficacy and safety of the placement of lumen-apposing metal stents (LAMS) for the treatment of gastrointestinal strictures. However, the optimum stent indwelling time is unclear. We reviewed the literature on endoscopic gastroenterostomy (GE) with a focus on the stent indwelling time and we described the first reported case of iatrogenic perforation six months after Axios stent placement. In the literature review (n = 239), the composite technical success rate and clinical success rate were 93.7% and 87.9%, respectively. The mean follow-up period was 191 days, and the mean stent indwelling time was 88 days. Among 13 studies (n = 202), the mean rate of complications was 13.4%. The principal complication was mis-deployment of the stent (4.5%). We report a case report of delayed iatrogenic perforation. A 59-year-old male patient with cystic dystrophy of the duodenum has been followed for several years. He presented with anorexia following duodenal obstruction and underwent endoscopic ultrasound-guided gastrojejunostomy. Six months later, he was referred to our center due to septic shock, and abdominal computed tomography revealed peritonitis secondary to a perforation of the small intestine, opposite the Axios stent. The mean LAMS indwelling time after GE was 88 days. To minimise the rate of adverse events, such as ulceration and mucosal overgrowth, regular abdominal computed tomography and endoscopy can be performed to evaluate the local effect of the stent. When the disease has resolved, the LAMS must be removed as soon as possible.


Assuntos
Derivação Gástrica , Endossonografia , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Ultrassonografia de Intervenção
18.
World J Surg ; 43(11): 2856-2864, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31384998

RESUMO

IMPORTANCE: In MEN1 patients with gastric and duodenopancreatic neuroendocrine tumors (GPD-NET), surgery aims to control secretions or to prevent metastatic spread, but after GPD-NET resection, postoperative mortality may be related to the surgery itself or to other associated MEN1 lesions with their own uncontrolled secretions or metastatic behavior. OBJECTIVE: To analyze the causes of death within 1 year following a GPD-NET resection in MEN1 patients. DESIGN: An observational study collecting data from the Groupe d'étude des Tumeurs Endocrines (GTE) database. The analysis considered the time between surgery and death (early deaths [<1 month after surgery] versus delayed deaths [beyond 1 month after surgery]) and the period (before 1990 vs after 1990). Causes of death were classified as related to GDP surgery, related to surgery for other MEN1 lesions or not related to MEN1 causes. SETTING: GTE database which includes 1220 MEN1 patients and 441 GPD-NET resections. PARTICIPANTS: Four hundred and forty-one GPD-NET resections. MAIN OUTCOME MEASURES: The primary end point was postoperative mortality within 1 year after surgery. RESULTS: Twenty-four patients met the inclusion criteria (2%). Median age at death was 50.5 years. Sixteen deaths occurred in the 30-day postoperative period (76%). Among the 8 delayed deaths, 3 occurred as a result of medical complications between 30 and 90 postoperative days. After 1990, mean age at death increased from 48 to 58 years (p = 0.09), deaths related to uncontrolled acid secretion disappeared (p < 0.001) and deaths related to associated MEN1 lesions increased from 8 to 54% (p = 0.16). CONCLUSION: Surgery and uncontrolled secretions remain the two main causes of death in MEN1 patients operated for a GPD-NET tumor. Improving the prognosis of these patients requires a strict evaluation of the secretory syndrome and MEN1 aggressiveness before GDP surgery.


Assuntos
Causas de Morte , Neoplasias Duodenais/cirurgia , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/patologia , Tumores Neuroendócrinos/mortalidade , Complicações Pós-Operatórias/mortalidade , Período Pós-Operatório , Prognóstico
19.
Langenbecks Arch Surg ; 402(2): 309-314, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28111697

RESUMO

PURPOSE: Aldosteronoma Resolution Score (ARS) is a predictive score for cure of hypertension after adrenalectomy for hyperaldosteronism and has been validated in American patients. The aim of the study was to validate this score in a French population. METHOD: Data concerning patients operated from 2002 to 2015 in 7 French University Hospitals were retrospectively collected. Diagnosis of Aldosterone-producing adenoma (APA) was confirmed with clinical and biochemical hyperaldosteronism and adrenal nodule on CT scan. Adrenal venous sampling was performed when CT failed to identify laterality. ARS is based on four variables: female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, number of antihypertensive medications ≤2. One point is attributed for the first three and 2 points for the last. Patients were considered as cured if they had no hypertension and no antihypertensive medications at least 6 months after surgery. Patients with bilateral adrenal hyperplasia were excluded. RESULTS: This multicenter study included 310 patients with APA. ARS and follow-up were obtained in 257 patients. 46.6% of patients were cured and potassium serum level was normalized in 97.7%. In multivariate analysis, odds ratio for female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, and number of antihypertensive medications ≤2 were 1.60 (p = 0.09), 1.77 (p = 0.04), 1.28 (p = 0.4), 3.41 (p < 0.001), respectively. Cure rate were, respectively, 22.2, 41.4 and 74% for patients with a score ARS 0-1, 2-3, 4-5. The area under the curve (AUC) of ARS was 0.715. CONCLUSION: ARS is not a predictive score efficient enough in a French population maybe due to different metabolic data and genetic conditions.


Assuntos
Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Hiperaldosteronismo/complicações , Hiperaldosteronismo/cirurgia , Hipertensão/sangue , Adenoma/sangue , Adenoma/complicações , Adolescente , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldosterona/sangue , Feminino , França , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/complicações , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
20.
Anal Bioanal Chem ; 407(28): 8433-43, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26427501

RESUMO

Despite effective treatments, relapse of colorectal cancer (CRC) is frequent, in part caused by the existence of tumor-initiating cells (TICs). Different subtypes of TICs, quiescent and activated, coexist in tumors, defining the tumor aggressiveness and therapeutic response. These subtypes have been sorted by hyperlayer sedimentation field-flow fractionation (SdFFF) from WiDr and HCT116 cell lines. On the basis of a new strategy, including TIC SdFFF sorting, 3D Matrigel amplification, and grafting of corresponding TIC colonies on the chick chorioallantoic membrane (CAM), specific tumor matrices could be obtained. If tumors had similar architectural structure with vascularization by the host system, they had different proliferative indices in agreement with their initial quiescent or activated state. Protein analysis also revealed that tumors obtained from a population enriched for "activated" TICs lost "stemness" properties and became invasive. In contrast, tumors obtained from a population enriched for "quiescent" TICs kept their stemness properties and seemed to be less proliferative and invasive. Then, it was possible to produce different kinds of tumor which could be used as selective supports to study carcinogenesis and therapy sensitivity.


Assuntos
Biomarcadores Tumorais/genética , Separação Celular/métodos , Neoplasias Colorretais/diagnóstico , Modelos Biológicos , Células-Tronco Neoplásicas/classificação , Animais , Biomarcadores Tumorais/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Separação Celular/instrumentação , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/patologia , Colágeno/química , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Fracionamento por Campo e Fluxo/instrumentação , Fracionamento por Campo e Fluxo/métodos , Expressão Gênica , Células HCT116 , Humanos , Queratina-20/genética , Queratina-20/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Laminina/química , Invasividade Neoplásica , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/patologia , Proteoglicanas/química
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