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1.
Dis Colon Rectum ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38924002

RESUMO

BACKGROUND: The double-stapled technique is the most common method of colorectal anastomosis in minimally invasive surgery. Several modifications to the conventional technique have been described aiming to reduce the intersection between the stapled lines, as the resulting lateral dog-ears are considered as possible risk factors for anastomotic leakage. OBJECTIVE: The purpose of this study was to analyze the outcomes of patients receiving conventional versus modified stapled colorectal anastomosis following minimally invasive surgery. DATA SOURCES: A systematic review was undertaken of the published literature. PubMed/MEDLINE, Web of Science, and EMBASE databases were screened up to July 2023. STUDY SELECTION: Relevant articles were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles reporting on the outcomes of patients with modified stapled colorectal reconstruction as compared to the conventional method of double-stapled anastomosis were included. INTERVENTIONS: Conventional double-stapling colorectal anastomosis and modified techniques with reduced intersection between the stapled lines were compared. MAIN OUTCOME MEASURES: The rate of anastomotic leak was the primary endpoint of interest. Perioperative details including postoperative morbidity were also appraised. RESULTS: There were 2537 patients from 12 studies included for data extraction, with no significant differences on age, body mass index and proportion of high American Society of Anesthesiologists Score between patients who had conventional versus modified techniques of reconstructions. The risk of anastomotic leak was 62% lower for the modified procedure compared to the conventional procedure (odds ratio = 0.38 [95% CI: 0.26, 0.56]. The incidences of overall postoperative morbidity (odds ratio = 0.57 [95% CI: 0.45, 0.73] and major morbidity (odds ratio = 0.48 [95% CI: 0.32, 0.72] following were significantly lower than following conventional double-stapled anastomosis. LIMITATIONS: The retrospective nature of most included studies is a main limitation, essentially due to the lack of randomization, and the risk of selection and detection bias. CONCLUSIONS: The available evidence supports the modification of the conventional double-stapled technique with elimination of one of both dog-ears as it is associated with lower incidence of anastomotic-related morbidity.

2.
HPB (Oxford) ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38853075

RESUMO

BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.

3.
Ann Surg Oncol ; 31(7): 4693-4694, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38709362

RESUMO

Central pancreatectomy (CP) is indicated for benign or low-grade pancreatic tumors located in the neck or proximal pancreatic body. This procedure is demanding and has a high rate of postoperative complications. Minimally invasive surgery is now commonly used for CP but it is still unclear whether the robotic approach offers any advantages over conventional pancreatic minimally invasive surgery. Most studies on robotic CP are limited to case reports or case series; however, there are two important studies on this topic. Currently, the evidence on robotic CP remains limited, making it challenging to draw definitive conclusions in favor of one technique over the other. The use of a robotic platform, with its integrated tools such as intraoperative ultrasound, can guide the surgeon in performing this technically demanding procedure in a safer manner. The controversy regarding the best minimally invasive surgery approach for CP is still ongoing and requires further research.


Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Pancreáticas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/prevenção & controle , Prognóstico
4.
Surg Oncol ; 54: 102081, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729088

RESUMO

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.


Assuntos
COVID-19 , Pancreatectomia , Neoplasias Pancreáticas , SARS-CoV-2 , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/epidemiologia , COVID-19/epidemiologia , Itália/epidemiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Terapia Neoadjuvante , Complicações Pós-Operatórias/epidemiologia , Seguimentos , Prognóstico , Pandemias
5.
Ann Surg Oncol ; 31(7): 4634, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38556599

RESUMO

BACKGROUND: Central pancreatectomy (CP) is a parenchymal-sparing technique indicated for the resection of selected lesions of the neck or proximal body of the pancreas.1,2 The risk of postoperative complications is theoretically doubled because the surgeon has to manage two cut surfaces of the pancreas. The video shows a fully robotic CP to treat a 62-year-old male patient with a mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreatic neck, using ultrasound (US) and Wirsung endoscopic evaluation to guide the pancreatic resection and ensure optimal resection margins. MATERIALS AND METHODS: A US-guided robotic CP was carried out, and an intraoperative endoscopic evaluation of the MPD was performed to determine the distal transection level. A transmesocolic, end-to-side, robot-sewn Wirsung-jejunostomy with internal MPD stenting was then created. The procedure was completed with a side-to-side jejunojejunostomy. RESULTS: The operative time was 290 min, with negligible blood loss. During the postoperative course, the patient experienced bleeding from a branch of the gastroduodenal artery with subsequent fluid collection, which was successfully treated with angioembolization and percutaneous drainage. He was discharged home on postoperative day 22. Final pathology revealed a non-invasive IPMN with low-grade dysplasia and free surgical margins. At 12 months of follow-up, the patient was doing well, with no evidence of local recurrence and endocrine or exocrine pancreatic insufficiency. CONCLUSIONS: The combination of robotic surgery with intraoperative US and Wirsungoscopy may offer distinct technical advantages for challenging pancreatectomies that follow the principles of parenchymal-sparing surgery.


Assuntos
Pancreatectomia , Ductos Pancreáticos , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Pancreatectomia/métodos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Ductos Pancreáticos/cirurgia , Ductos Pancreáticos/patologia , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Prognóstico
6.
Int J Med Robot ; : e2596, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37937476

RESUMO

BACKGROUND: Robotic distal pancreatectomy (RDP) is associated with a lower conversion rate and less blood loss than laparoscopic distal pancreatectomy (LDP). LDP has similar oncological outcomes as open surgery in PDAC. The aim of this study was to compare perioperative and oncological outcomes in obese patients with RDP versus LDP for PDAC. MATERIALS AND METHODS: Retrospectively, all obese patients who underwent RDP or LDP for PDAC between 2012 and 2022 at 12 international expert centres were included. RESULTS: out of 372, 81 patients were included. All baseline features were comparable between the two groups. RDP was associated with decreased blood loss (495mlLDP vs. 188mlRDP; p = 0.003), lower conversion rate (13.5%RDP vs. 36.4%LDP; p = 0.019) and lower rate of Clavien-Dindo ≥3 complications (13.5%RDP vs. 36.4%LDP; p = 0.019). Overall and disease-free survival were comparable. CONCLUSIONS: In obese patients with left-sided PDAC, the robotic approach was associated with improved intraoperative outcomes and fewer severe complications.

7.
Surg Endosc ; 37(11): 8384-8393, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37715084

RESUMO

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Pancreatectomia , Resultado do Tratamento , Laparoscopia/efeitos adversos , Duração da Cirurgia , Tempo de Internação , Estudos Retrospectivos
8.
J Laparoendosc Adv Surg Tech A ; 33(6): 579-585, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37130329

RESUMO

Background: A preliminary analysis from the COVID-Advanced Gastrointestinal Cancer Surgical Treatment (AGICT) study showed that the rate of minimally invasive surgery (MIS) for elective and urgent procedures did not decrease during the pandemic year. In this article, we aimed to perform a subgroup analysis using data from the COVID-AGICT study to evaluate the trend of MIS during the COVID-19 pandemic period in Italy. Methods: This study was conducted collecting data of MIS patients from the COVID-AGICT database. The primary endpoint was to demonstrate whether the SARS-CoV-2 pandemic scenario reduced MIS for elective treatment of gastrointestinal cancer (GIC) in Italy in 2020. The secondary endpoint was to evaluate the impact of the pandemic period on perioperative outcomes in the MIS group. Results: In the pandemic year, 62% of patients underwent surgery with a minimally invasive approach, compared to 63% in 2019 (P = .23). In 2020, the proportion of patients undergoing elective MIS decreased compared to the previous year (80% versus 82%, P = .04), and the rate of urgent MIS did not differ between the 2 years (31% and 33% in 2019 and 2020 - P = .66). Colorectal cancer was less likely to be treated with MIS approach during 2020 (78% versus 75%, P < .001). Conversely, the rate of MIS pancreatic resection was higher in 2020 (28% versus 22%, P < .002). Conversion to an open approach was lower in 2020 (7.2% versus 9.2% - P = .01). Major postoperative complications were similar in both years (11% versus 11%, P = .9). Conclusion: In conclusion, although MIS for elective treatment of GIC in Italy was reduced during the COVID-19 pandemic period, our study revealed that the overall proportion of MIS (elective and urgent) and postoperative outcomes were comparable to the prepandemic period. ClinicalTrial.gov (NCT04686747).


Assuntos
COVID-19 , Neoplasias Gastrointestinais , Humanos , Neoplasias Gastrointestinais/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento
9.
World J Surg ; 47(9): 2207-2212, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37210424

RESUMO

BACKGROUND: The adoption of robotic surgery for esophageal cancer has been expanding rapidly over the recent years. In the setting of two-field esophagectomy, different techniques exist for intrathoracic esophagogastric anastomosis, although the superiority of one over another has not been clearly demonstrated. Potential benefits in terms of anastomotic leakage and stenosis have been reported in association with a linear-stapled anastomosis as compared to the more widespread techniques of circular mechanical and hand-sewn reconstructions, however, there is still limited reported evidence on its application to robotic surgery. We here report our fully robotic technique of side-to-side, semi-mechanical anastomosis. METHODS: All consecutive patients undergoing fully robotic esophagectomy featuring intrathoracic side-to-side stapled anastomosis by a single surgical team were included in this analysis. Operative technique is detailed, and perioperative data are assessed. RESULTS: A total of 49 patients were included. There were no intraoperative complications and no conversion occurred. The rate of overall postoperative morbidity was 25, 14% being the relative rate of major complications. With anastomotic-related morbidity in particular, one patient developed minor anastomotic leakage. CONCLUSIONS: Our experience demonstrates that a linear, side-to-side fully robotic stapled anastomosis can be created with a high technical success and minimal incidence of anastomosis-related morbidity.


Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Humanos , Esofagectomia/efeitos adversos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Anastomose Cirúrgica/efeitos adversos , Neoplasias Esofágicas/complicações , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
10.
J Robot Surg ; 17(5): 2135-2140, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37247120

RESUMO

The advantages of using the robotic platform may not be clearly evident in left colectomies, where the surgeon operates in an "open field" and does not routinely require intraoperative suturing. Current evidences are based on limited cohorts reporting conflicting outcomes regarding robotic left colectomies (RLC). The aim of this study is to report a bi-centric experience with robotic left colectomy in order to help in defining the role of the robotic approach for these procedures. This is a bi-centric propensity score matched study including patients who underwent RLC or laparoscopic left colectomy (LLC) between January 1, 2012 and May 1, 2022. RLC patients were matched to LLC patients in a 1:1 ratio. Main outcomes were conversion to open surgery and 30-day morbidity. In total, 300 patients were included. Of 143 (47.7%) RLC patients, 119 could be matched. After matching, conversion rate (4.2 vs. 7.6%, p = 0.265), 30-day morbidity (16.1 vs. 13.7%, p = 0.736), Clavien-Dindo grade ≥ 3 complications (2.4 vs 3.2%, p = 0.572), transfusions (0.8 vs. 4.0%, p = 0.219), and 30-day mortality (0.8 vs 0.8%, p = 1.000) were comparable for RLC and LLC, respectively. Median operative time was longer for RLC (296 min 260-340 vs. 245, 195-296, p < 0.0001). Early oral feeding, time to first flatus, and hospital stay were similar between groups. RLC has safety parameters as well as conversion to open surgery comparable with standard laparoscopy. Operative time is longer with the robotic approach.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Pontuação de Propensão , Laparoscopia/métodos , Colectomia/efeitos adversos , Colectomia/métodos , Duração da Cirurgia , Tempo de Internação , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
11.
Surg Oncol ; 47: 101907, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36924550

RESUMO

BACKGROUND: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic. METHOD: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined. RESULTS: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001). CONCLUSIONS: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.


Assuntos
COVID-19 , Neoplasias Colorretais , Neoplasias Pancreáticas , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Neoplasias Colorretais/cirurgia
12.
Am J Emerg Med ; 66: 174.e3-174.e5, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36653228

RESUMO

Pylephlebitis is defined as a septic thrombophlebitis of the portal vein, usually secondary to infection in regions contiguous to or drained by the portal system. Although extremely uncommon in the modern era, pylephlebitis still carries an appreciable risk of severe morbidity and mortality, if unrecognized and left untreated. Herein we report the case of severe pylephlebitis in a patient with acute sigmoid diverticulitis. Although highly elusive, prompt diagnosis is crucial to ensure appropriate management and limit associated morbidity.


Assuntos
Diverticulite , Hepatopatias , Tromboflebite , Humanos , Diverticulite/complicações , Tromboflebite/diagnóstico por imagem , Tromboflebite/tratamento farmacológico , Tromboflebite/etiologia , Veia Porta/diagnóstico por imagem , Veias Mesentéricas
13.
Dig Surg ; 39(5-6): 232-241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36198281

RESUMO

INTRODUCTION: Despite progressive improvements in technical skills and instruments that have facilitated surgeons performing intracorporeal gastro-jejunal and jejuno-jejunal anastomoses, one of the big challenging tasks is handsewn knot tying. We analysed the better way to fashion a handsewn intracorporeal enterotomy closure after a stapled anastomosis. METHODS: All 579 consecutive patients from January 2009 to December 2019 who underwent minimally invasive partial gastrectomy for gastric cancer were retrospectively analysed. Different ways to fashion intracorporeal anastomoses were investigated: robotic versus laparoscopic approach; laparoscopic high definition versus three-dimensional versus 4K technology; single-layer versus double-layer enterotomies. Double-layer enterotomies were analysed layer by layer, comparing running versus interrupted suture; the presence versus absence of deep corner suture; and type of suture thread. RESULTS: Significantly lower rates of bleeding (p = 0.011) and leakage (p = 0.048) from gastro-jejunal anastomosis were recorded in the double-layer group. Barbed suture thread was significantly associated with reduced intraluminal bleeding and leakage rates both in the first (p = 0.042 and p = 0.010) and second layer (p = 0.002 and p = 0.029). CONCLUSIONS: Double-layer sutures using barbed suture thread both in first and second layer to fashion enterotomy closure result in lower intraluminal bleeding and anastomotic leak rates.


Assuntos
Laparoscopia , Técnicas de Sutura , Humanos , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Intestinos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Suturas
14.
J Immunother Cancer ; 10(9)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36096533

RESUMO

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized cancer immunotherapy. However, most patients with cancer fail to respond clinically. One potential reason is the accumulation of immunosuppressive transforming growth factor ß (TGFß) in the tumor microenvironment (TME). TGFß drives cancer immune evasion in part by inducing regulatory T cells (Tregs) and limiting CD8+ T cell function. Glycoprotein-A repetitions predominant (GARP) is a cell surface docking receptor for activating latent TGFß1, TGFß2 and TGFß3, with its expression restricted predominantly to effector Tregs, cancer cells, and platelets. METHODS: We investigated the role of GARP in human patients with cancer by analyzing existing large databases. In addition, we generated and humanized an anti-GARP monoclonal antibody and evaluated its antitumor efficacy and underlying mechanisms of action in murine models of cancer. RESULTS: We demonstrate that GARP overexpression in human cancers correlates with a tolerogenic TME and poor clinical response to ICB, suggesting GARP blockade may improve cancer immunotherapy. We report on a unique anti-human GARP antibody (named PIIO-1) that specifically binds the ligand-interacting domain of all latent TGFß isoforms. PIIO-1 lacks recognition of GARP-TGFß complex on platelets. Using human LRRC32 (encoding GARP) knock-in mice, we find that PIIO-1 does not cause thrombocytopenia; is preferentially distributed in the TME; and exhibits therapeutic efficacy against GARP+ and GARP- cancers, alone or in combination with anti-PD-1 antibody. Mechanistically, PIIO-1 treatment reduces canonical TGFß signaling in tumor-infiltrating immune cells, prevents T cell exhaustion, and enhances CD8+ T cell migration into the TME in a C-X-C motif chemokine receptor 3 (CXCR3)-dependent manner. CONCLUSION: GARP contributes to multiple aspects of immune resistance in cancer. Anti-human GARP antibody PIIO-1 is an efficacious and safe strategy to block GARP-mediated LTGFß activation, enhance CD8+ T cell trafficking and functionality in the tumor, and overcome primary resistance to anti-PD-1 ICB. PIIO-1 therefore warrants clinical development as a novel cancer immunotherapeutic.


Assuntos
Neoplasias , Microambiente Tumoral , Animais , Linfócitos T CD8-Positivos/metabolismo , Glicoproteínas , Humanos , Inibidores de Checkpoint Imunológico , Proteínas de Membrana , Camundongos , Fator de Crescimento Transformador beta/metabolismo
15.
HPB (Oxford) ; 24(12): 2045-2052, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36167766

RESUMO

BACKGROUND: Among patients with distant metastatic melanoma, the site of metastases is the most significant predictor of survival and visceral-nonpulmonary metastases hold the highest risk of poor outcomes. However, studies demonstrate that a significant percentage of patients may be considered candidates for resection with improved survival over nonsurgical therapeutic modalities. We aimed at analyzing the results of resection in patients with melanoma metastasis to the pancreas by assessing the available evidence. METHODS: The PubMed/MEDLINE, WoS, and Embase electronic databases were systematically searched for articles reporting on the surgical treatment of pancreatic metastases from melanoma. Relevant data from included studies were assessed and analyzed. Overall survival was the primary endpoint of interest. Surgical details and oncological outcomes were also appraised. RESULTS: A total of 109 patients treated surgically for pancreatic metastases were included across 72 articles and considered for data extraction. Overall, patients had a mean age of 51.8 years at diagnosis of pancreatic disease. The cumulative survival was 71%, 38%, and 26% at 1, 3 and 5 years after pancreatectomy, with an estimated median survival of 24 months. Incomplete resection and concomitant extrapancreatic metastasis were the only factors which significantly affected survival. Patients in whom the pancreas was the only metastatic site who received curative resection exhibited significantly longer survival, with a 1-year, 3-year, and 5-year survival rates of 76%, 43%, and 41%, respectively. CONCLUSION: Within the limitations of a review of non-randomized reports, curative surgical resection confers a survival benefit in carefully selected patients with pancreatic dissemination of melanoma.


Assuntos
Melanoma , Neoplasias Pancreáticas , Humanos , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Taxa de Sobrevida
17.
Surg Oncol ; 43: 101816, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35849995

RESUMO

BACKGROUND: How best to manage colorectal cancer patients presenting resectable synchronous liver metastasis is still a matter of debate. A number of different available therapeutic strategies exist, with significant differences in terms of optimal timing and/or sequence of resection of the primary tumor and liver disease [1]. Over the last years, simultaneous resections are increasingly adopted for properly selected patients [1-3]. However, the application of minimally invasive surgery to combined colorectal and liver surgery is still controversial, especially in the case of liver disease requiring technically demanding resections [2,3]. VIDEO: The presented video illustrates the details of a single-docking robotic right colectomy combined with ultrasound-guided, parenchymal-sparing resection of liver segments 6 and 7, as performed to treat a patient with locally advanced colorectal cancer and metastatic disease isolated to the right liver. Port placement strategy and main instrumentation employed are illustrated in Fig. 1, and Fig. 2, respectively. The total duration of surgery was 380 minutes. The hepatic hilum was encircled to allow extracorporeal Pringle maneuver during liver resection, though no clamping was eventually required. Right colectomy with central vascular ligation was thus carried out and an intracorporeal ileocolic anastomosis performed. The patient had an uneventful postoperative course. CONCLUSIONS: When feasible, minimally invasive simultaneous resection may offer distinct advantages over conventional surgery while respecting the tenets of appropriate oncological resection [2,3]. The well-known benefits of minimally invasive surgery, including shorter overall hospital length of stay, reduced morbidity, and lower blood loss, are combined with the need to recover from a single major surgery. Robotic resection may be particularly suited for technically challenging procedures, such as colectomy combined with liver metastasectomies with unfavorable anatomical accessibility [3,4].


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Hepatectomia/métodos , Humanos , Laparoscopia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos
19.
Int J Med Robot ; 18(3): e2383, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35189021

RESUMO

BACKGROUND: Robotic surgery may facilitate complex procedures such as right colectomy with complete mesocolic excision (CME) and shorten the learning curve. This study aimed to compare senior and junior surgeons' results in performing robotic right colectomy (RRC) with CME and intracorporeal anastomosis for right colon cancer. MATERIALS AND METHODS: Between January 2015 and April 2020, a total of 161 patients underwent RRC with CME. After propensity score matching, two groups of 31 patients for each surgeon were formed. Intraoperative, postoperative and pathological outcomes were the variables assessed. RESULTS: No statistically significant difference was recorded between the two groups. The senior surgeon experienced 16.1% minor complications (Clavien-Dindo I-II) and 3.2% major complications (Clavien-Dindo III-IV), while the novice surgeon reported 19.3% and 3.2% rates of minor and major adverse events, respectively. CONCLUSIONS: After a structured training protocol, a novice may obtain comparable results to an expert in performing RRC with CME.


Assuntos
Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Cirurgiões , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Humanos , Laparoscopia/métodos , Excisão de Linfonodo , Duração da Cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
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