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1.
Br J Surg ; 111(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960881

RESUMO

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).


Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Excisão de Linfonodo , Procedimentos Cirúrgicos Robóticos , Cirurgia Torácica Vídeoassistida , Humanos , Esofagectomia/métodos , Esofagectomia/efeitos adversos , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Feminino , Pessoa de Meia-Idade , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Neoplasias Esofágicas/cirurgia , Excisão de Linfonodo/métodos , Excisão de Linfonodo/efeitos adversos , Idoso , Carcinoma de Células Escamosas do Esôfago/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Nervo Laríngeo Recorrente/cirurgia , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Adulto
2.
Ann Surg Oncol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926213

RESUMO

BACKGROUND: The prognosis for patients with esophageal cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery has shown improvement in recent years. We sought to identify the critical factors contributing to enhanced survival outcomes. PATIENTS AND METHODS: We retrospectively examined 427 patients with esophageal cancer treated with nCRT and esophagectomy across two periods: P1 (from 1 January 2004 to 31 December 2011) and P2 (from 1 January 2012 to 31 December 2017). The introduction of the CROSS regimen and total meso-esophagectomy in P2 prompted an evaluation of their effects on perioperative outcomes and overall survival (OS). RESULTS: During P2, the occurrence of recurrent laryngeal nerve palsy increased significantly from 3.9 to 16.8% (p < 0.001), while pneumonia and in-hospital mortality rates remained unchanged. The median OS improved from 19.2 to 29.2 months (p < 0.001) between P1 and P2. Multivariable analysis identified higher nodal yields and the achievement of major response as favorable prognostic factors. Conversely, an involved circumferential resection margin (CRM), an advanced ypN stage, and pneumonia were independently associated with poor outcomes. Patients treated during P2 had a lower prevalence of involved CRM (10% vs. 25.1%, p < 0.001), a higher rate of major response (52.7% vs. 34.8%, p < 0.01), and a greater nodal yield (27.8 vs. 10.9, p < 0.001). CONCLUSIONS: The clinical outcomes following nCRT and surgery have improved significantly over time. This progress can be attributed to multiple factors, with the primary drivers being the refinement of nCRT protocols and the application of radical surgery.

3.
JTCVS Tech ; 25: 160-169, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899114

RESUMO

Objective: Robot-assisted thoracoscopic surgery typically necessitates the use of multiple ports. The new single-port robotic system (da Vinci SP system) platform is designed to perform uniportal surgery. The purpose of this clinical trial is to evaluate the feasibility, efficacy, and safety of the da Vinci SP system when used for anatomical lung resection. Methods: Patients diagnosed with clinical stage I lung cancer requiring anatomical lung resections were considered eligible for this trial. The primary outcome measure was the rate of conversion, whereas the secondary objective focused on assessing the incidence of perioperative complications. Results: The study included 35 patients with a median age of 63 years (range, 48-74 years). Of these, 30 underwent lobectomy and 5 received segmentectomy. All surgeries were successfully performed using a subcostal approach, except for 1 patient, who required a thoracotomy conversion due to bleeding (conversion rate: 2.9%). The median docking time was 2 minutes (range, 1-8 minutes). For the 34 patients who completed uniportal surgery, the median total operating time was 194 minutes (range, 63-405 minutes), whereas the console time was 153 minutes (range, 93-267 minutes). The median number of harvested nodes was 13 (range, 5-37), while the median number of nodal stations was 6 (rang, 4-8). There were no in-hospital fatalities, and the median postoperative stay was 3 days (range, 2-12 days). Conclusions: This study demonstrates the feasibility and safety of using the da Vinci SP system for anatomical lung resection through a subcostal approach. ClinicalTrialsgov identifier: NCT05535712.

6.
Br J Surg ; 111(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38721902

RESUMO

OBJECTIVE: Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS: Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS: For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION: The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia , Quimiorradioterapia Adjuvante , Quimiorradioterapia , Europa (Continente) , Resultado do Tratamento
7.
Innovations (Phila) ; : 15569845241248641, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725287

RESUMO

OBJECTIVE: In recent years, there has been an increasing focus on minimally invasive mediastinal surgery using a trans-subxiphoid single-port thoracoscopic approach. Despite its potential advantages, the widespread adoption of this method has been hindered by the intricate surgical maneuvers required within the confined retrosternal space. Robotic surgery offers the potential to overcome the limitations inherent in the thoracoscopic technique. METHODS: This was a clinical trial (NCT05455840) to evaluate the feasibility and safety of utilizing the da Vinci® SP system (Intuitive Surgical, Sunnyvale, CA, USA) for trans-subxiphoid single-port surgery in patients with anterior mediastinal disease. The primary endpoints encompassed conversion rates and the secondary endpoints included the occurrence of perioperative complications. RESULTS: Between August 2022 and April 2023, a total of 15 patients (7 men and 8 women; median age = 56 years, interquartile range [IQR]: 49 to 65 years) underwent trans-subxiphoid robotic surgery using da Vinci SP platform for maximal thymectomy (n = 2) or removal of anterior mediastinal masses (n = 13). All surgical procedures were carried out with success, with no need for conversion to open surgery or the creation of additional ports. The median docking time was 2 min (IQR: 1 to 4 min), while the console time had a median of 152 min (IQR: 95 to 191 min). There were no postoperative complications and patients experienced a median postoperative hospital stay of 2 days with no unplanned 30-day readmission. CONCLUSIONS: This study shows that trans-subxiphoid single-port robotic surgery employing the da Vinci SP system in patients with anterior mediastinal disease is clinically viable with acceptable safety and short-term outcomes.

8.
Ann Surg Oncol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780688

RESUMO

BACKGROUND: In patients with locally advanced esophageal cancer who had undergone chemoradiotherapy (CRT), the limitations of radiological evaluation may necessitate surgical exploration to ascertain disease resectability. Upon intraoperative confirmation of T4b disease (sT4b), the optimal management strategy remains unclear. While some surgeons may opt against resection, others advocate for palliative esophagectomy (PE). Regrettably, the current literature does not provide a consensus on the most effective approach for managing these intricate cases. METHODS: The study cohort consisted of 68 patients with esophageal squamous cell carcinoma (ESCC) who presented with sT4b disease following CRT. The perioperative outcomes and overall survival (OS) were compared between patients who underwent PE (n = 56) and those who received an open-close (OC) procedure (n = 12). RESULTS: Patients who underwent an OC procedure experienced a shorter hospital stay (16.5 vs. 28.8 days; p = 0.052) and showed a non-significant reduction in the rate of major complications (33.9% vs. 25%; p = 0.549) and in-hospital mortality (0% vs. 5.4%; p = 0.412) than those who received PE; however, PE was associated with a superior 2-year OS rate than OC (9.6% vs. 0%; p = 0.009). In multivariable analysis, a pretreatment clinical stage of II/III (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.31-0.87; p = 0.013) and PE with retrosternal reconstruction (HR 0.38, 95% CI 0.15-0.49; p = 0.010) were independently associated with a more favorable OS. CONCLUSION: PE with retrosternal reconstruction may be a feasible approach for patients with ESCC exhibiting sT4b disease after CRT.

9.
Asian J Surg ; 47(6): 2623-2624, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531735

RESUMO

TECHNIQUE: The surgical management for high-output postoperative chylothorax typically necessitates ligation of the thoracic duct (TD) above the leak site and/or sealing the leak with a clip. However, pinpointing these structures during subsequent surgeries can be challenging due to their variable course and the presence of traumatized tissues surrounding the leak area. In response to this, we have developed a novel, fluorescence-guided technique that significantly enhances intraoperative identification of the leak point and the TD. This method was applied in the case of a 52-year-old man suffering from refractory chylothorax following a previous lung cancer surgery. This study documents the surgical procedure and includes a video vignette for a comprehensive understanding. RESULTS: A bilateral inguinal lymph node injection of saline (10 mL), guided by ultrasound and containing 2.5 mg/mL indocyanine green (ICG), was administered 20 min prior to surgery. During thoracoscopic exploration, the leak point was precisely pinpointed in the right paratracheal area by transitioning from bright light to fluorescent mode. The TD was clearly identified, and upon ligation, there was no further leakage of fluorescent lymph, indicating a successful closure of the lymphatic structure. The surgery proceeded uneventfully, and the patient was able to resume oral intake on the third postoperative day. There was no evidence of recurring symptoms, leading to his discharge. CONCLUSION: The intralymphatic injection of ICG offers a rapid visualization of the TD's anatomy and can effectively pinpoint the leak point, even amidst traumatized tissues. Moreover, it provides prompt feedback on the efficacy of ligation.


Assuntos
Quilotórax , Verde de Indocianina , Complicações Pós-Operatórias , Cirurgia Torácica Vídeoassistida , Humanos , Quilotórax/cirurgia , Quilotórax/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Verde de Indocianina/administração & dosagem , Cirurgia Torácica Vídeoassistida/métodos , Fluorescência , Ligadura/métodos , Ducto Torácico/cirurgia , Neoplasias Pulmonares/cirurgia , Cirurgia Assistida por Computador/métodos
10.
Cancers (Basel) ; 16(6)2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38539444

RESUMO

PURPOSE: The textbook outcome (TBO), a multidimensional indicator that reflects an optimal perioperative course, has emerged as a significant prognostic variable in surgical oncology. Our study aimed to assess the occurrence and determinants of TBO following minimally invasive esophagectomy (MIE) for cancer. METHODS: A total of 945 patients who had undergone MIE at two high-volume centers between 2008 and 2022 were analyzed. Multivariable logistic regression analysis was applied to identify the independent predictors of TBO. The potential selection bias associated with choosing between different MIE techniques-namely, robotic esophagectomy (RE) and video-assisted thoracoscopic esophagectomy (VATE)-was addressed by applying inverse probability of treatment weighting (IPTW). RESULTS: TBO was realized in 46.6% of cases (n = 440), correlating with markedly better overall and disease-free survival. Multivariable analysis showed that treatment with RE (odds ratio (OR) = 1.527; 95% confidence interval (CI) = 1.149-2.028) was associated with a higher likelihood of achieving TBO, whereas a Charlson Comorbidity Index (CCI) of 2 or higher showed an opposite association (CCI2: OR = 0.687, 95% CI = 0.483-0.977; CCI ≥ 3: OR = 0.604, 95% CI = 0.399-0.915). The advantage of RE in attaining a higher rate of TBO, compared to VATE, remained statistically significant after applying IPTW, with rates of 53.3% for RE and 42.2% for VATE. Notably, RE contributed to a greater probability of thorough lymph node dissection, resection with negative margins, and the avoidance of major complications. CONCLUSION: TBO was realized in 46.6% of the patients who underwent MIE for cancer. Patients with a lower CCI and those who received RE were more likely to achieve TBO.

11.
J Robot Surg ; 18(1): 21, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217569

RESUMO

Anterior mediastinal procedures are increasingly being performed using robot-assisted thoracic surgery (RATS) or video-assisted thoracoscopic surgery (VATS). While both approaches have shown superior outcomes compared to open surgery, their comparative benefits are not as distinct. The aim of this retrospective study was to bridge this knowledge gap using a multicenter dataset. Patients who underwent elective minimally invasive surgery for anterior mediastinal disease between 2015 and 2022 were deemed eligible. The study participants were grouped based on whether a robot was used or not, and perioperative outcomes were compared. To mitigate selection bias, inverse probability of treatment weighting (ITPW) was applied using the propensity score. The final analysis included 312 patients (RATS = 120; VATS = 192). Following the application of IPTW, RATS was found to be associated with a longer operating time (215.3 versus 139.31 min, P < 0.001), fewer days with a chest tube (1.96 versus 2.61 days, P = 0.047), and a shorter hospital stay (3.03 versus 3.91 days, P = 0.041) compared to VATS. Subgroup analyses indicated that the benefit of RATS in reducing the length of hospital stay was particularly pronounced in patients with tumors larger than 6 cm (mean difference [MD] = - 2.28 days, P = 0.033), those diagnosed with myasthenia gravis (MD = - 3.84 days, P = 0.002), and those who underwent a trans-subxiphoid surgical approach (MD = - 0.81 days, P = 0.04). Both VATS and RATS are safe and effective approaches for treating anterior mediastinal disease. However, RATS holds distinct advantages over VATS including shorter hospital stays and reduced chest tube drainage periods.


Assuntos
Doenças do Mediastino , Procedimentos Cirúrgicos Robóticos , Humanos , Cirurgia Torácica Vídeoassistida/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Resultado do Tratamento , Timectomia/métodos , Doenças do Mediastino/cirurgia
12.
Ann Surg Oncol ; 31(3): 1546-1552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37989958

RESUMO

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy is a serious complication of esophagectomy that affects the patient's phonation and the ability to prevent life-threatening aspiration events. The aim of this single-center, retrospective study was to investigate the clinical course of left RLN palsy and to identify the main prognostic factors for recovery. METHODS: The study cohort consisted of 85 patients who had developed left RLN palsy after minimally invasive McKeown esophagectomy. Vocal cord function was assessed in all participants through laryngoscopic examinations, both in the immediate postoperative period and during follow-up. Permanent palsy was defined as no evidence of recovery after 6 months. Univariate and multivariable logistic regression analyses were applied to evaluate the associations between different variables and the outcome of palsy. RESULTS: Twenty-two (25.8%) patients successfully recovered from left RLN palsy. On multivariable logistic regression analysis, active smoking (odds ratio [OR] 0.335, p = 0.038) and the use of thoracoscopic surgery (vs. robotic surgery; OR 0.264, p = 0.028) were identified as independent unfavorable predictors for recovery from palsy. The estimated rates of recovery derived from a logistic regression model for patients harboring two, one, or no risk factors were 13.16%, 31.15-34.75%, and 61.39%, respectively. CONCLUSION: Only one-quarter of patients who had developed left RLN palsy after minimally invasive McKeown esophagectomy were able to fully recover. Smoking habits and the surgical approach were identified as key determinants of recovery. Patients harboring adverse prognostic factors are potential candidates for early intervention strategies.


Assuntos
Neoplasias Esofágicas , Paralisia das Pregas Vocais , Humanos , Estudos Retrospectivos , Paralisia das Pregas Vocais/etiologia , Esofagectomia/efeitos adversos , Nervo Laríngeo Recorrente/cirurgia , Prognóstico , Neoplasias Esofágicas/cirurgia
14.
Cancer Imaging ; 23(1): 109, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932848

RESUMO

BACKGROUND: To investigate the value of [18F]FDG-PET/MRI in predicting treatment response and survival in patients with primary M0 esophageal squamous cell carcinoma. METHODS: Patients with esophageal squamous cell carcinoma received [18F]FDG-PET/MRI at baseline and during neoadjuvant or definitive chemoradiotherapy. The treatment response was classified according to the Response Evaluation Criteria for Solid Tumors 1.1. We used Kaplan-Meier and Cox regression analyses to assess the association between PET/MRI parameters and overall survival (OS) or progression-free survival (PFS). RESULTS: We included 40 M0 patients in the final analysis. The volume transfer constant (Ktrans) from baseline PET/MRI (area under the curve (AUC) = 0.688, P = 0.034) and total lesion glycolysis (TLG) from baseline PET/MRI (AUC = 0.723, P = 0.006) or interim PET/MRI (AUC = 0.853, P < 0.001) showed acceptable AUC for predicting treatment response. The TLG from interim PET/MRI (interim TLG, P < 0.001) and extracellular volume fraction (Ve) on interim PET/MRI (interim Ve, P = 0.001) were identified as independent prognostic factors for OS. Baseline Ve (P = 0.044) and interim TLG (P = 0.004) were significant predictors of PFS. The c-indices of the prognostic models combining interim TLG with Ve for predicting OS, and baseline Ve and interim TLG for predicting PFS were 0.784 and 0.699, respectively. These values were significantly higher than the corresponding c-indices of the TNM staging system (P = 0.002 and P = 0.047, respectively). CONCLUSIONS: Combining the baseline and interim [18F]FDG-PET/MRI qualitative imaging parameters aids in predicting the prognosis of patients with M0 esophageal squamous cell carcinoma. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (identifier: NCT05855291 and NCT05855278).


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/patologia , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
16.
JTCVS Tech ; 21: 251-258, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37854845

RESUMO

Objectives: Endoscopic thoracic sympathectomy may be complicated by the onset of disabling compensatory sweating (CS). The objective of this case series is to report the 2-year outcomes after robotic sympathetic trunk reconstruction (STR) for the reversal of CS in patients who had undergone endoscopic thoracic sympathectomy. Methods: We prospectively followed-up a total of 23 patients who had undergone robotic STR because of intolerable CS between October 2017 and January 2021. A visual analog scale ranging from 0 to 10 (with 10 indicating the highest degree) was used to assess the severity of CS at different anatomical locations, thermoregulatory alterations, and gustatory hyperhidrosis. Measurements were performed before STR and at 6-month and 2-year follow-up. Results: The mean age of the study participants was 43.3 ± 7.8 years, and 20 (87%) were men. The reversal procedure was performed after a mean of 19.6 ± 7.8 years from endoscopic thoracic sympathectomy. In all patients, nerve defects were successfully bridged using sural nerves (mean length, 9.7 cm on the right and 9.8 cm on the left). No cases of Horner syndrome were noted. At 6 postoperative months, the severity of CS decreased significantly at all body surface areas. The observed improvements were effectively maintained at 24 post-STR months. There was no evidence of either recurrent hyperhidrosis at the primary site or transition of CS to other anatomical locations. Similar improvements were evident for thermoregulatory alterations and gustatory hyperhidrosis. Conclusions: Robotic STR is safe and effective in reversing intolerable CS after endoscopic thoracic sympathectomy.

17.
Transl Oncol ; 38: 101785, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37713975

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. METHODS: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. RESULTS: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). CONCLUSIONS: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

18.
Cancers (Basel) ; 15(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37627076

RESUMO

BACKGROUND: This retrospective study examined outcomes in esophageal squamous cell carcinoma (ESCC) patients who did not undergo surgical resection after neoadjuvant chemoradiotherapy (nCRT). METHODS: Patients receiving nCRT between 2012 and 2020 were divided into two groups: group 1 (scheduled surgery) and group 2 (no surgery). Group 2 was further categorized into subgroups based on reasons for not proceeding to surgery: group 2a (disease progression), group 2b (poor general conditions), and group 2c (patient refusal). Overall survival (OS) was the primary outcome. RESULTS: Group 1 comprised 145 patients, while subgroups 2a, 2b, and 2c comprised 24, 16, and 31 patients, respectively. The 3-year OS rate was significantly lower in group 2 compared with group 1 (34% versus 56%, p < 0.001). A subgroup analysis showed varying 3-year OS rates: 13% for group 2a, 25% for group 2b, and 58% for group 2c (p < 0.001). Propensity score matching for group 2c and group 1 revealed no significant difference in 3-year OS rates (p = 0.91). CONCLUSION: One-third of ESCC patients receiving nCRT did not undergo surgical resection. Overall survival in this group was generally poorer, except for those who refused surgery (group 2c).

19.
J Thorac Dis ; 15(7): 3800-3810, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37559654

RESUMO

Background: Few studies have compared robotic-arm-assisted unisurgeon uniportal surgeries with conventional human-assisted uniportal video-assisted thoracoscopic surgeries (VATSs) in terms of surgical efficacy and patient safety. In the present study, we compared the aforementioned surgeries. Methods: We explored two robotic endoscope holders-a passive robotic platform (ENDOFIXexo, EA group) and a pedal-controlled active robotic platform (MTG-100, MA group)-for unisurgeon uniportal surgeries and compared the surgical outcomes with those of human-assisted uniportal surgeries (HA group) in 228 patients with a lung lesion (size, <5 cm). The primary parameters for this comparison were surgical efficacy, patient safety, and short-term patient outcomes. Results: No significant differences were observed among the EA, MA, and HA groups. The success rate of robotic-arm-assisted unisurgeon uniportal wedge resection was 100%, regardless of the group. No major differences were noted in preparation time between the EA and MA groups. Segmentectomy was more favorable in the EA group than in the MA group. The rates of surgical conversion were 5% and 60% in the EA and MA groups, respectively. The EA and MA groups did not differ considerably from the HA group in terms of postoperative complications. Conclusions: Unisurgeon uniportal wedge resection may be effectively performed using a robotic endoscope holder, without the need for any human assistants with an expert hand. However, the rate of surgical conversion increases with the complexity of uniportal anatomic resections. The passive platform appears to be more suitable for unisurgeon uniportal surgery than the active pedal-controlled platform given the equipment in contemporary operating rooms.

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