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1.
Colorectal Dis ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886887

RESUMEN

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.

2.
Surgery ; 175(6): 1508-1517, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38609785

RESUMEN

BACKGROUND: The observed increase in the incidence of complicated diverticulitis may lead to the performance of more emergency surgeries. This study aimed to assess the rate and risk factors of emergency surgery for sigmoid diverticulitis. METHOD: The primary outcomes were the rate of emergency surgery for sigmoid diverticulitis and its associated risk factors. The urgent or elective nature of the surgical intervention was provided by the surgeon and in accordance with the indication for surgical treatment. A mixed logistic regression with a random intercept after multiple imputations by the chained equation was performed to consider the influence of missing data on the results. RESULTS: Between 2010 and 2021, 6,867 patients underwent surgery for sigmoid diverticulitis in the participating centers, of which one-third (n = 2317) were emergency cases. In multivariate regression analysis with multiple imputation by chained equation, increasing age, body mass index <18.5 kg/m2, neurologic and pulmonary comorbidities, use of anticoagulant drugs, immunocompromised status, and first attack of sigmoid diverticulitis were independent risk factors for emergency surgery. The likelihood of emergency surgery was significantly more frequent after national guidelines, which were implemented in 2017, only in patients with a history of sigmoid diverticulitis attacks. CONCLUSION: The present study highlights a high rate (33%) of emergency surgery for sigmoid diverticulitis in France, which was significantly associated with patient features and the first attack of diverticulitis.


Asunto(s)
Diverticulitis del Colon , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , Francia/epidemiología , Anciano , Diverticulitis del Colon/cirugía , Diverticulitis del Colon/epidemiología , Urgencias Médicas , Adulto , Enfermedades del Sigmoide/cirugía , Anciano de 80 o más Años , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Tratamiento de Urgencia/estadística & datos numéricos
3.
J Visc Surg ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38604931

RESUMEN

Lumbar hernia is a rare disease, which can be acquired spontaneously or secondarily (post-traumatically, postoperatively…) or congenitally. It results from the existence of areas of weakness between the different muscles forming the posterior abdominal wall: the deep-seated Grynfeltt triangle and the superficial Jean-Louis Petit triangle.

4.
Cancers (Basel) ; 16(1)2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38201660

RESUMEN

We analyzed whether preoperative 18F-FDG PET/CT adds to conventional primary staging in patients with presumed non-metastatic colonic cancer (CC). The prognostic role of 18F-FDG uptake in the primary tumor was evaluated after a mean follow-up of 15 years. Patients with a new diagnosis of presumed localized CC were prospectively enrolled and underwent presurgical 18F-FDG PET/CT. For each colon lesion, SUVmax, SUVpeak, TLG, and MTV were assessed and tested as prognostic factors. Forty-eight patients were included. Post-surgery pathology identified a total of 103 colon lesions, including 58 invasive adenocarcinomas, 4 in situ adenocarcinomas, 3 adenomas with high-grade dysplasia, and 38 adenomas with low-grade dysplasia. Per lesion sensitivity, specificity, positive (PPVs) and negative predictive values (NPVs) for colonic primary tumor detection were 78%, 97%, 98%, and 73% for conventional workup, and 94%, 87%, 92%, and 89% for 18F-FDG PET/CT. Only sensitivity was significantly different between 18F-FDG PET/CT and conventional workup. PET detected an additional ten pathological colonic lesions in seven patients. SUVmax, SUVpeak, and TLG showed significant differences between invasive adenocarcinomas, in situ adenocarcinomas, and high-grade dysplasia compared to low-grade dysplasia. There was a statistically significant difference between pT1-pT2 and pT3-pT4 adenocarcinomas. On patient-based analysis, sensitivity, specificity, PPV, and NPV for nodal staging were 22%, 84%, 44%, and 65% for CECT, and 33%, 90%, 67%, and 70% for 18F-FDG PET/CT, without a statistically significant difference. PET/CT also identified unknown metastatic spread and one synchronous lung cancer in four patients. Overall, 18F-FDG PETCT had an additional diagnostic value in 11 out of 48 patients (23%). 18F-FDG uptake of the primary tumor did not predict nodal or distant metastases. The difference in disease-free survival categorized by median SUVmax, SUVpeak, TLG, and MTV was not significant. Finally, preoperative 18F-FDG PET/CT is valuable in detecting potential colon lesions not visualized by conventional workups, especially in cases of incomplete colonoscopy. It effectively highlights distant metastases but exhibits limitations for N staging. Mainly due to the relatively small sample size, the quantitative analysis of 18F-FDG uptake in the primary tumor did not reveal any association with recurrence or disease-free survival, adding no significant prognostic information.

6.
Surg Endosc ; 38(1): 24-46, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37985490

RESUMEN

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.


Asunto(s)
Hernia Inguinal , Hernia Ventral , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Pérdida de Sangre Quirúrgica , Hernia Inguinal/cirugía , Hernia Inguinal/complicaciones , Hernia Ventral/cirugía , Hernia Ventral/complicaciones , Herniorrafia/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Infección de la Herida Quirúrgica/cirugía
8.
Int J Colorectal Dis ; 38(1): 276, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38040936

RESUMEN

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.


Asunto(s)
COVID-19 , Diverticulitis del Colon , Divertículo , Humanos , Anastomosis Quirúrgica/métodos , Colon Sigmoide/cirugía , Colostomía/métodos , Diverticulitis del Colon/cirugía , Diverticulitis del Colon/complicaciones , Divertículo/complicaciones , Complicaciones Posoperatorias , Recto/cirugía , Estudios Retrospectivos
10.
Langenbecks Arch Surg ; 408(1): 344, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37642752

RESUMEN

BACKGROUND: Parastomal incisional hernia (PH) is a frequent complication following the creation of an ileal conduit (IC), and it can be a significant detriment to quality of life. The aim of this study was to evaluate outcomes of PH repair following IC for urinary diversion. METHOD: A multicenter retrospective study was conducted of 6 academic hospitals in France. The study's population included patients who underwent surgical treatment for parastomal hernia following IC creation from 2013 to 2021. RESULTS: Fifty-one patients were included in the study. Median follow up was 15.3 months. Eighteen patients presented with a recurrence (35%), with a median time to recurrence of 11.1 months. The vast majority of PH repair was performed through an open approach (88%). With regard to technique, Keyhole was the most reported technique (46%) followed by Sugarbaker (22%) and suture only (20%). The Keyhole technique was associated with a higher risk of recurrence compared to the Sugarbaker technique (52% vs 10%, p = 0.046). Overall, there was a 7.8% rate of major complications without a statistical difference between PH repair techniques for major complications. CONCLUSION: Surgical treatment of parastomal hernia following IC was associated with a high risk of recurrence. Novel surgical approaches to PH repair should be considered.


Asunto(s)
Hernia Incisional , Derivación Urinaria , Humanos , Cistectomía/efectos adversos , Hernia Incisional/etiología , Hernia Incisional/cirugía , Calidad de Vida , Estudios Retrospectivos , Derivación Urinaria/efectos adversos
12.
Pleura Peritoneum ; 8(1): 11-18, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37020473

RESUMEN

Objectives: Current recommendations regarding enhanced recovery programs (ERPs) after complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are based on a low level of evidence. The aim of this study is to evaluate the effect of implementing an adapted ERP for CCRS and HIPEC in a referral center. Methods: We conducted a study with a prospective group of 44 patients (post-ERP group) who underwent CCRS with HIPEC between July 2016 and June 2018, the period during which ERP was implemented. This group was compared to a second retrospective group of 21 patients who underwent CCRS with HIPEC between June 2015 and June 2016, during which ERP was not yet implemented (pre-ERP group). Results: The ERP compliance rate was 65% in the post-ERP group. The hospital length of stay (HLS) was shorter in the post-ERP group: 24.9 days (IQR 11-68, pre-ERP group) vs. 16.1 days (IQR 6-45, post-ERP group), as was the major morbidity rate (pre-ERP group=33.3% vs. post-ERP group=20.5%). The nasogastric tube, urinary catheter and abdominal drains were all retrieved faster in the post-ERP group. Conclusions: The implementation of an adapted ERP after CCRS with HIPEC procedures reduces morbidity and shortens the HLS.

13.
Hernia ; 27(5): 1165-1177, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36753035

RESUMEN

PURPOSE: Groin hernia repair is one of the most frequent operation performed worldwide. Chronic postoperative inguinal pain (CPIP) is the most common and challenging complication after surgical repair with subsequent high socio-economic impact. The aim of this study was to compare the one-year CPIP rates between Lichtenstein, trans-inguinal pre-peritoneal (TIPP), trans-abdominal pre-peritoneal (TAPP) and totally extra-peritoneal (TEP) repair techniques on the French Hernia Registry. METHODS: Between 2011 and 2021, 15,161 primary groin hernia repairs with 1-year follow-up were available on the register. Using propensity score (PS) matching, matched pairs were formed. Each group was compared in pairs independently; Lichtenstein versus TIPP, TEP and TAPP, TIPP versus TEP and TAPP and finally TEP versus TAPP. RESULTS: After PS matching analysis, Lichtenstein group showed disadvantage over TIPP, TAPP and TEP groups with significantly more CPIP at one year (15.2% vs 9.6%, p < 0.0001; 15.9% vs. 10.0%, p < 0.0001 and 16.1% vs. 12.4%, p = 0.002, respectively). The 1-year CPIP rates were similar comparing TIPP versus TAPP and TEP groups (9.3% vs 10.5%, p = 0.19 and 9.8% vs 11.8%, p = 0.05, respectively). There was significantly less CPIP rate after TAPP versus TEP repair (1.00% vs 11.9%, p = 0.02). CONCLUSION: This register-based study confirms the higher CPIP risk after Lichtenstein repair compared to the pre-peritoneal repair techniques. TIPP leads to comparable CPIP rates than TAPP and TEP repairs.


Asunto(s)
Hernia Inguinal , Laparoscopía , Humanos , Hernia Inguinal/cirugía , Hernia Inguinal/complicaciones , Ingle/cirugía , Laparoscopía/métodos , Puntaje de Propensión , Herniorrafia/métodos , Dolor Postoperatorio/etiología , Sistema de Registros , Mallas Quirúrgicas/efectos adversos , Resultado del Tratamiento
14.
Obes Surg ; 33(1): 17-24, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36422757

RESUMEN

INTRODUCTION: Bariatric surgery can become technically challenging in the setting of liver steatosis and hepatomegaly. The protein sparing modified fast (PSMF) diet helps in achieving rapid weight loss. The aim of this study is to explore the results of a preoperative PSMF diet on liver volume and steatosis as well as on intraoperative and postoperative complications in patients with hepatomegaly undergoing Roux-en-Y gastric bypass (RYGB). METHODS: Between January 2010 and January 2021, 713 patients undergoing RYGB as a primary bariatric surgery were divided in two groups. Those with a measured liver length above 16 cm and or evidence of liver steatosis on ultrasound (group 1) were offered a preoperative PSMF diet while the remaining (group 2) proceeded directly to surgery. Between January 2010 and April 2012, patients included in group 1 had liver volume measurements on magnetic resonance imaging the day before the diet was started and the day before the surgery. For the length of the study, intraoperative and postoperative data were recorded for both groups. RESULTS: Five days of preoperative PSMF diet resulted in a significant reduction of total and left liver volume (15.8% and 21% respectively, p < 0.001). There was no difference in intraoperative bleeding and conversion rate or postoperative complication rate between both groups. CONCLUSION: The PSMF diet helps in achieving a rapid decrease in liver volume. Patients with hepatomegaly initially thought to be at a higher risk of intraoperative complications reached comparable rates to patients without hepatomegaly after the diet regimen without any impact on the postoperative course.


Asunto(s)
Cirugía Bariátrica , Hígado Graso , Derivación Gástrica , Obesidad Mórbida , Humanos , Obesidad Mórbida/cirugía , Hepatomegalia/complicaciones , Cirugía Bariátrica/métodos , Derivación Gástrica/métodos , Dieta , Complicaciones Posoperatorias/etiología , Hígado Graso/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento
15.
Eur J Surg Oncol ; 49(2): 384-391, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36372618

RESUMEN

BACKGROUND: Sarcopenia is recognized as a negative prognostic factor in several cancers. The aim of this study was to investigate the impact of nutritional support with feeding jejunostomy (FJ) on the occurrence of sarcopenia and how it may affect postoperative short-term outcomes and long-term survival outcomes in patients undergoing esophagectomy for oesogastric junction adenocarcinoma (OJA). METHODS: Patients with OJA were included. The presence of sarcopenia was determined using cutoff values of the total cross-sectional muscle tissue measured on CT scan. We analyzed risk factors for sarcopenia occurrence and the impact of preoperative sarcopenia on postoperative results, overall survival and disease-free survival. RESULTS: A total of 124 patients were eligible for analysis. Ninety-one patients underwent surgery after chemotherapy, and 72 of them received preoperative FJ. Among the 91 patients, 21 patients (23.0%) were sarcopenic after preoperative chemotherapy. Multivariate analysis showed that FJ is a protective factor against sarcopenia occurrence. Overall survival was significantly different between sarcopenic and nonsarcopenic patients (median survival = 33.7 vs. 58.6 months, respectively, p = 0.04), and sarcopenia occurrence was an independent risk factor for overall survival in patients who underwent surgery (HR = 3.02; CI 95% 1.55-5.9; p < 0.005). Subgroup analyses showed no differences in overall survival between patients who presented sarcopenia despite nutritional prehabilitation with a FJ and patients excluded from surgery in palliative situations (median survival = 21.9 vs. 17.2 months, respectively, p = 0.46). CONCLUSION: The persistence of sarcopenia after preoperative chemotherapy despite renutrition with FJ could be a selection factor to propose curative surgery for OJA.


Asunto(s)
Adenocarcinoma , Sarcopenia , Humanos , Sarcopenia/epidemiología , Pronóstico , Estudios Transversales , Selección de Paciente , Adenocarcinoma/complicaciones , Apoyo Nutricional , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología
17.
Ann Surg Oncol ; 29(12): 7568-7576, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35882692

RESUMEN

BACKGROUND: Survival of patients affected by colorectal cancer peritoneal metastases (CRC-PM) can be improved with combined complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Two chemotherapeutic agents are mainly used: mitomycin C (MMC) and oxaliplatin. A recent prospective randomized clinical trial showed that oxaliplatin-based HIPEC does not improve survival compared with CCRS alone. The purpose of our study was to compare the survival effectiveness of MMC versus oxaliplatin-based HIPEC using a homogeneous surgical technique and drug protocol. METHODS: This retrospective monocentric study included all patients prospectively registered for having undergone CCRS and HIPEC using MMC or oxaliplatin for CRC-PM in Strasbourg University Hospital, France, from December 2004 until December 2019. MMC-based HIPEC and oxaliplatin-based HIPEC groups were compared with an inverse probability of treatment weighting. RESULTS: A total of 137 patients were included. Groups were comparable for all baseline characteristics except for peritoneal carcinomatosis index. In the weighted multivariate analysis, disease-free survival (DFS) and peritoneal disease-free survival (PDFS) were significantly higher in the MMC-based HIPEC group compared with the oxaliplatin-based HIPEC group with a hazard ratio of 0.74 (CI 95% 0.56-0.98), p = 0.035 and 0.59 (CI 95% 0.40-0.98), p = 0.0084, respectively. There was no difference in overall survival or postoperative morbidity between groups. CONCLUSIONS: These results favor a superiority of MMC for DFS and PDFS in comparison with oxaliplatin in HIPEC after CCRS in treatment with curative intent for CRC-PM.


Asunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Colorrectales/patología , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Humanos , Hipertermia Inducida/métodos , Mitomicina , Oxaliplatino , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Tasa de Supervivencia
18.
Medicine (Baltimore) ; 100(44): e27665, 2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34871242

RESUMEN

ABSTRACT: The aim of this prospective study was to assess the influence of preoperative life satisfaction on objective and subjective outcomes after elective colorectal surgery. Preoperative life satisfaction was assessed using a validated questionnaire (Échelle de Mesure des Manifestations du Bien-Être Psychologique). Postoperative quality of life was assessed by the Cleveland Global Quality of Life and QLQ-C30. Number of footsteps was recorded from preoperative day 5 to postoperative day 3. Physical activity, length of stay, and complications were compared between patients with low and high preoperative life satisfaction. Fifty patients were included. There was no difference between the 2 groups concerning postoperative objective (length of stay, complications, and number of footsteps) and subjective (Cleveland Global Quality of Life and QLQ-C30) recovery. In conclusion, preoperative life satisfaction of colorectal surgery patients had no influence on outcomes and physical activity in colorectal surgery.


Asunto(s)
Neoplasias Colorrectales/cirugía , Cirugía Colorrectal , Neoplasias Colorrectales/psicología , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Estudios Prospectivos , Calidad de Vida
19.
Pharmaceutics ; 13(9)2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34575561

RESUMEN

The reasons behind the poor efficacy of transition metal-based chemotherapies (e.g., cisplatin) or targeted therapies (e.g., histone deacetylase inhibitors, HDACi) on gastric cancer (GC) remain elusive and recent studies suggested that the tumor microenvironment could contribute to the resistance. Hence, our objective was to gain information on the impact of cisplatin and the pan-HDACi SAHA (suberanilohydroxamic acid) on the tumor substructure and microenvironment of GC, by establishing patient-derived xenografts of GC and a combination of ultrasound, immunohistochemistry, and transcriptomics to analyze. The tumors responded partially to SAHA and cisplatin. An ultrasound gave more accurate tumor measures than a caliper. Importantly, an ultrasound allowed a noninvasive real-time access to the tumor substructure, showing differences between cisplatin and SAHA. These differences were confirmed by immunohistochemistry and transcriptomic analyses of the tumor microenvironment, identifying specific cell type signatures and transcription factor activation. For instance, cisplatin induced an "epithelial cell like" signature while SAHA favored a "mesenchymal cell like" one. Altogether, an ultrasound allowed a precise follow-up of the tumor progression while enabling a noninvasive real-time access to the tumor substructure. Combined with transcriptomics, our results underline the different intra-tumoral structural changes caused by both drugs that impact differently on the tumor microenvironment.

20.
Molecules ; 26(17)2021 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-34500819

RESUMEN

Metal complexes have been used to treat cancer since the discovery of cisplatin and its interaction with DNA in the 1960's. Facing the resistance mechanisms against platinum salts and their side effects, safer therapeutic approaches have been sought through other metals, including ruthenium. In the early 2000s, Michel Pfeffer and his collaborators started to investigate the biological activity of organo-ruthenium/osmium complexes, demonstrating their ability to interfere with the activity of purified redox enzymes. Then, they discovered that these organo-ruthenium/osmium complexes could act independently of DNA damage and bypass the requirement for the tumor suppressor gene TP53 to induce the endoplasmic reticulum (ER) stress pathway, which is an original cell death pathway. They showed that other types of ruthenium complexes-as well complexes with other metals (osmium, iron, platinum)-can induce this pathway as well. They also demonstrated that ruthenium complexes accumulate in the ER after entering the cell using passive and active mechanisms. These particular physico-chemical properties of the organometallic complexes designed by Dr. Pfeffer contribute to their ability to reduce tumor growth and angiogenesis. Taken together, the pioneering work of Dr. Michel Pfeffer over his career provides us with a legacy that we have yet to fully embrace.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Compuestos Organometálicos/farmacología , Animales , Antineoplásicos/química , Humanos , Compuestos Organometálicos/química , Osmio/química , Rutenio/química
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