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1.
Int J Colorectal Dis ; 36(5): 929-939, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33118101

RESUMO

PURPOSE: To analyze different types of management and one-year outcomes of anastomotic leakage (AL) after elective colorectal resection. METHODS: All patients with anastomotic leakage after elective colorectal surgery with anastomosis (76/1,546; 4.9%), with the exclusion of cases with proximal diverting stoma, were followed-up for at least one year. Primary endpoints were as follows: composite outcome of one-year mortality and/or unplanned intensive care unit (ICU) admission and additional morbidity rates. Secondary endpoints were as follows: length of stay (LOS), one-year persistent stoma rate, and rate of return to intended oncologic therapy (RIOT). RESULTS: One-year mortality rate was 10.5% and unplanned ICU admission rate was 30.3%. Risk factors of the composite outcome included age (aOR = 1.08 per 1-year increase, p = 0.002) and anastomotic breakdown with end stoma at reoperation (aOR = 2.77, p = 0.007). Additional morbidity rate was 52.6%: risk factors included open versus laparoscopic reoperation (aOR = 4.38, p = 0.03) and ICU admission (aOR = 3.63, p = 0.05). Median (IQR) overall LOS was 20 days (14-26), higher in the subgroup of patients reoperated without stoma. At 1 year, a stoma persisted in 32.0% of patients, higher in the open (41.2%) versus laparoscopic (12.5%) reoperation group (p = 0.04). Only 4 out of 18 patients (22.2%) were able to RIOT. CONCLUSION: Mortality and/or unplanned ICU admission rates after AL are influenced by increasing age and by anastomotic breakdown at reoperation; additional morbidity rates are influenced by unplanned ICU admission and by laparoscopic approach to reoperation, the latter also reducing permanent stoma and failure to RIOT rates. TRIAL REGISTRATION: ClinicalTrials.gov # NCT03560180.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Cirurgia Colorretal/efeitos adversos , Humanos , Reoperação
2.
Int J Cancer ; 147(9): 2597-2610, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483858

RESUMO

In our study, we investigated the role of CD39 on tumor-infiltrating CD8+ T lymphocytes (CD8+ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T-cell exhaustion, we demonstrated a divergent functional activity in CD39+ CD8+ TILs. On the one hand, CD39+ CD8+ TILs (as compared to their CD39- counterparts) produced significantly lower IFN-γ and IL-2 amounts, expressed higher PD-1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD-1 expression. Therefore, CD39+ CD8+ TILs, including those co-expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A>G), as a genetic factor associated with CD39 expression in CD8+ TILs. Finally, we demonstrated that compounds inhibiting CD39-related ATPases improved CD39+ CD8+ T-cell effector function ex vivo, and that CD39+ CD8+ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39+ CD8+ T-cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8+ TILs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apirase/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apirase/antagonistas & inibidores , Apirase/genética , Células Cultivadas , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/metabolismo
3.
Surgeon ; 14(6): 337-344, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27395014

RESUMO

AIM: The optimal treatment for advanced gallbladder cancer, in particular T2 stage cancer, is unclear. The use of "radical cholecystectomy" or more extended procedures with extra-hepatic bile duct resection are matter of debate. Due to the lack of consensus regarding the oncological significance of routine extra-hepatic bile duct (EBD) resection for gallbladder carcinoma, we decided to perform a systematic review investigating the real benefit of this procedure focusing on the primary outcomes of overall survival and disease-free survival. METHODS: A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central according to the PRISMA statement guidelines for conducting and reporting systematic reviews. Multiple primary and secondary outcomes were analyzed. RESULTS: The selected articles included 424 patients who underwent routine EBD resection without bile duct infiltration. Only two papers discussed the number of dissected lymph nodes during EBD resection for gallbladder carcinoma. Four of the seven included papers reported on tumor involvement in lymph nodes at rates ranging between 39% and 83%. All of the studies included in this systematic review reported on results of overall survival. In general, 5-years OS rate of the EBD-resected patients was not significantly different than that of the EBD-preservation group, while the mobility was significantly higher in the EBD resection group. CONCLUSIONS: Routine EBD resection in gallbladder cancer patients without bile duct infiltration is not associated with improved overall survival, improved lymph-node harvesting or with minor recurrence rate, but it is associated with higher morbidity rates.


Assuntos
Colecistectomia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/mortalidade , Humanos
4.
J Minim Access Surg ; 12(3): 199-208, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27279389

RESUMO

BACKGROUND: The oncologic validity of laparoscopic-assisted distal gastrectomy (LADG) in the treatment of advanced gastric cancer (AGC) remains controversial. This study is a systematic review and meta-analysis of the available evidence. MATERIALS AND METHODS: A comprehensive search was performed between 2008 and 2014 to identify comparative studies evaluating morbidity/mortality, oncologic surgery-related outcomes, recurrence and survival rates. Data synthesis and statistical analysis were carried out using RevMan 5.2 software. RESULTS: Eight studies with a total of 1456 patients were included in this analysis. The complication rate was lower in LADG [odds ratio (OR) 0.59; 95% confidence interval (CI) = 0.42-0.83; P < 0.002]. The in-hospital mortality rate was comparable (OR 1.22; 95% CI = 0.28-5-29, P = 0.79). There was no significant difference in the number of harvested lymph nodes, resection margins, cancer recurrence rate, cancer-related mortality or overall and disease-free survival (OS and DFS, respectively) rates between the laparoscopic and the open groups (P > 0.05). CONCLUSION: The current study supports the view that LADG for AGC is a feasible, safe and effective procedure in selected patients. Adequate lymphadenectomy, resection margins, recurrence, cancer-related mortality and long-term outcomes appear equivalent to open distal gastrectomy (ODG).

5.
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
6.
Ann Ital Chir ; 94: 161-167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37203284

RESUMO

BACKGROUND: In recent years, the role of laparoscopic approach in the surgical treatment of right colon cancer has increased. Results comparing the different techniques of ileocolic anastomoses are controversial, with studies only reporting some advantages of the intracorporeal laparoscopic technique. The aim of this study is to compare the outcomes between laparoscopic versus open hemicolectomy for right colon cancer, focusing on anastomotic techniques (intracorporeal vs extracorporeal in the laparoscopic procedure, and manual vs mechanical in the laparotomic procedure). METHODS: This is a retrospective single center study enrolling patients with right colon cancer from January 2016 to December 2020. Primary endpoint of the study was the rate of anastomotic leak (AL). RESULTS: A total of 161 patients who underwent right hemicolectomy were enrolled: 91 were performed with laparoscopic technique, and 70 with open technique. Overall, AL occurred in 15 pts (9.3%). We observed 4 AL in intracorporeal (12.9%) and 6 in extracorporeal (10%) anastomoses, respectively. In the laparotomy group 5 patients (7.1%) developed AL, of which 3 (5.7%) and 2 (11.1%) manually and mechanically performed, respectively. CONCLUSIONS: Based on our findings, laparoscopic hemicolectomy has a higher incidence of anastomotic leak. In the laparoscopic group, we observed the lowest rate of AL with extracorporeal mechanical anastomosis. When performed extracorporeally with open technique, hand-sewn anastomosis has better results than mechanical. KEY WORDS: Anastomosis, Cancer, Ileotransverse, Leakage, Right Colectomy.


Assuntos
Neoplasias do Colo , Laparoscopia , Humanos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Estudos Retrospectivos , Colectomia/efeitos adversos , Colectomia/métodos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/complicações , Laparoscopia/métodos , Resultado do Tratamento
7.
Pathol Res Pract ; 237: 154002, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35849868

RESUMO

Approximately 20% of locally advanced rectal cancers treated with neoadjuvant therapy achieve a pathologic complete response, but approximately 10% of them present residual nodal metastases (ypT0N+). We aimed this research to compare the survival rates of ypT0/ypTisN+ and stage 3a rectal cancer patients. A large multicenter study recently investigated ypT0/ypTis rectal cancers treated between 2005 and 2015 in Italy and Spain. ypT0/ypTisN+ were selected and compared with stage 3a rectal cancers treated at the same institutions with upfront surgery (ySICO group). Additionally, the SEER database was searched for patients with stage 3a rectal cancers treated with surgery in the same years. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were analyzed using Kaplan-Meier curves and random survival forest analysis (RSF). The ySICO study population consisted of 19 ypT0/2ypTisN+ (mean follow-up 41.8 months) and 72 Stage 3a patients (mean follow-up 56.9 months). These subgroups were comparable, but stage 3a patients were treated more frequently with adjuvant therapy (90.5% vs 61.9%, p 0.0001). No significant differences were reported between the ySICO subgroups for the OS, DFS, and DSS curves. When the 1213 SEER patients were added to Stage 3a, the RFS model failed to differentiate OS between groups that presented identical survival. Root analysis showed that adjuvant therapy was the only variable differentiating OS and DSS in the ySICO population. These findings suggest that ypT0/ypTisN+ and stage 3a rectal cancers could be ranked together based on their similar outcomes and pathologic assessment, and they stress the importance of adjuvant therapy in patients presenting with residual nodal metastases.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Intervalo Livre de Doença , Reto/patologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Surg Today ; 41(4): 596-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21431502

RESUMO

Adenoid cystic carcinoma (ACC) is a relatively rare tumor of the salivary glands, accounting for approximately 5%-10% of all salivary gland tumors. An important feature of ACCs is the long clinical course with a high rate of distant metastases, with an incidence of more than 40% for ACC of submandibular glands. The preferential sites of metastases are the lung and bone, followed by the brain and liver. Most liver metastases are derived from nonparotid ACCs, and the presentation is often related to local recurrence or metastases to other organs. We herein report the case of a patient with liver metastases treated by a hepatectomy, which occurred 18 months after the primary resection of an ACC of the submandibular gland. We furthermore review the literature concerning the management of these tumors.


Assuntos
Carcinoma Adenoide Cístico/secundário , Carcinoma Adenoide Cístico/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias da Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Evolução Fatal , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
9.
Clin J Gastroenterol ; 14(1): 115-122, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33044637

RESUMO

Gastrointestinal neuroendocrine tumor (NET) associated with a metachronous intestinal adenocarcinoma is rare. We report the case of a 71-year-old man with an ileal NET. Patient has previously undergone a left colectomy for sigmoid cancer. We report a complete review both of the metachronous and synchronous NET. A comprehensive systematic literature search in PubMed, EMBASE, and MEDLINE identified a total of 35 relevant studies. This study includes an analysis of review articles, case reports, case series, retrospective studies and population-based studies. In the English literature to date, there are 21 case reports (19 synchronous cases and 2 metachronous cases), 3 case series and 3 review articles, and less than 10 retrospective studies or population-based studies. A total of 31 patients in 24 articles were included in the study: 28 patients with a synchronous gastrointestinal NET and colorectal adenocarcinoma and 3 patients with metachronous gastrointestinal NET and colorectal adenocarcinoma. The incidence of synchronous cancer (particularly for colorectal and gastric cancer) with a gastrointestinal NET ranges from 10 to 50%, while for the metachronous ones it is still unclear. This is the third metachronous case report and the first descriptive case of gastrointestinal NET diagnosed 2 years after a colorectal adenocarcinoma. An endoscopic follow-up program for gastrointestinal NET patients and/or for first-degree relatives of NET patients appears recommendable.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Tumores Neuroendócrinos , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Idoso , Neoplasias Colorretais/cirurgia , Humanos , Masculino , Neoplasias Primárias Múltiplas/cirurgia , Segunda Neoplasia Primária/cirurgia , Tumores Neuroendócrinos/cirurgia , Estudos Retrospectivos
10.
Sci Rep ; 11(1): 7150, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785761

RESUMO

In the West, more than one third of newly diagnosed subjects show metastatic disease in gastric cancer (mGC) with few care options available. Gastrectomy has recently become a subject of debate, with some evidence showing advantages in survival beyond the sole purpose of treatment tumor-related complications. We investigated the survival benefit of different strategies in mGC patients, focusing on the role and timing of gastrectomy. Data were extracted from the SEER database. Groups were determined according to whether patients received gastrectomy, chemotherapy, supportive care. Patients receiving a multimodality treatment were further divided according to timing of surgery, whether performed before (primary gastrectomy, PG) or after chemotherapy (secondary gastrectomy, SG). 16,596 patients were included. Median OS was significantly higher (p < 0.001) in the SG (15 months) than in the PG (13 months), gastrectomy alone (6 months), and chemotherapy (7 months) groups. In the multivariate analysis, SG showed better OS (HR = 0.22, 95%CI = 0.18-0.26, p < 0.001) than PG (HR = 0.25, 95%CI = 0.23-0.28, p < 0.001), gastrectomy (HR = 0.40, 95%CI = 0.36-0.44, p < 0.001), and chemotherapy (HR = 0.42, 95%CI = 0.4-0.44, p < 0.001). The survival benefits persisted even after the PSM analysis. This study shows survival advantages of gastrectomy as multimodality strategy after chemotherapy. In selected patients, SG can be proposed to improve the management of stage IV disease.


Assuntos
Gastrectomia/métodos , Neoplasias Gástricas/terapia , Estômago/cirurgia , Idoso , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Seguimentos , Gastrectomia/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Prognóstico , Programa de SEER/estatística & dados numéricos , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento
11.
Eur J Surg Oncol ; 47(8): 2046-2052, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33757649

RESUMO

OBJECTIVE: The endpoint of the present study was to evaluate the outcomes of short-course radiotherapy (SCRT) and SCRT with delayed surgery (SCRT-DS) on a selected subgroup of frail patients with locally advanced middle/low rectal adenocarcinoma. METHODS: From January 2008 to December 2018, a total of 128 frail patients with locally advanced middle-low rectal adenocarcinoma underwent SCRT and subsequent restaging for eventual delayed surgery. Rates of complete pathological response, down-staging, disease free survival (DFS) and overall survival (OS) were analyzed. RESULTS: 128 patients completed 5 × 5 Gy pelvic radiotherapy. 69 of these were unfit for surgery; 59 underwent surgery 8 weeks (average time: 61 days) after radiotherapy. Downstaging of T occurred in 64% and down-staging of N in 50%. The median overall survival (OS) of SCRT alone was 19.5 months. The 1-year, 2-year, 3-year and 5-year OS was 48%, 22%, 14% and 0% respectively. In the surgical group, the median disease-free survival (DFS) and median OS were, respectively, 67 months (95% CI 49.8-83.1 months) and 72.1 months (95% CI 57.5-86.7 months). The 1, 2, 3, 5-year OS was 88%, 75%, 51%, 46%, respectively. Post-operative morbidity was 22%, mortality was 3.4%. CONCLUSIONS: Frail patients with advanced rectal cancer are often "unfit" for long-term neoadjuvant chemoradiation. A SCRT may be considered a valid option for this group of patients. Once radiotherapy is completed, patients can be re-evaluated for surgery. If feasible, SCRT and delayed surgery is the best option for frail patients.


Assuntos
Adenocarcinoma/terapia , Fragilidade/complicações , Protectomia/métodos , Radioterapia Conformacional/métodos , Neoplasias Retais/terapia , Abscesso/epidemiologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Dor do Câncer/etiologia , Dor do Câncer/fisiopatologia , Colectomia , Fístula do Sistema Digestório/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/complicações , Neoplasias Retais/patologia , Neoplasias Retais/fisiopatologia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Taxa de Sobrevida
12.
World J Gastrointest Surg ; 13(11): 1463-1483, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34950434

RESUMO

BACKGROUND: Gastric cancer is an aggressive disease with frequent lymph node (LN) involvement. The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs. This threshold has been the subject of great debate, not only for the extent of surgery but also for more appropriate staging. The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number. Furthermore, studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastric cancer. AIM: To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation. METHODS: Eligible patients were identified from the Surveillance, Epidemiology, and End Results database. Those with stage II-III gastric cancer were considered for inclusion. Three groups were compared based on the number of analyzed LNs. They were inadequate LN assessment (ILA, < 16 LNs), adequate LN assessment (ALA, 16-29 LNs), and optimal LN assessment (OLA, ≥ 30 LNs). The main outcomes were overall survival (OS) and cancer-specific survival. Data were analyzed by the Kaplan-Meier product-limit method, log-rank test, hazard risk, and Cox proportional univariate and multivariate models. Propensity score matching (PSM) was used to compare the ALA and OLA groups. RESULTS: The analysis included 11607 patients. Most had advanced T stages (T3 = 48%; T4 = 42%). The pathological AJCC stage distribution was IIA = 22%, IIB = 18%, IIIA = 26%, IIIB = 22%, and IIIC = 12%. The overall sample divided by the study objective included ILA (50%), ALA (35%), and OLA (15%). Median OS was 24 mo for the ILA group, 29 mo for the ALA group, and 34 mo for the OLA group (P < 0.001). Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group [ALA hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.79-0.88, P < 0.001 and OLA HR = 0.73, 95%CI: 0.68-0.79, P < 0.001]. The OS outcome was confirmed by multivariate analysis (ALA HR = 0.68, 95%CI: 0.64-0.71, P < 0.001 and OLA: HR = 0.48, 95%CI: 0.44-0.52, P < 0.001). A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group (OS: OLA median = 34 mo vs ALA median = 26 mo, P < 0.001, which was confirmed by univariate analysis (HR = 0.81, 95%CI: 0.75-0.89, P < 0.001) and multivariate analysis: (HR = 0.71, 95%CI: 0.65-0.78, P < 0.001). CONCLUSION: Proper nodal staging is a critical issue in gastric cancer. Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.

13.
Oncogene ; 38(11): 1860-1875, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30367149

RESUMO

Metabolic reprogramming is a typical feature of cancer cells aimed at sustaining high-energetic demand and proliferation rate. Here, we report clear-cut evidence for decreased expression of the adipose triglyceride lipase (ATGL), the first and rate-limiting enzyme of triglyceride hydrolysis, in both human and mouse-induced hepatocellular carcinoma (HCC). We identified metabolic rewiring as major outcome of ATGL overexpression in HCC-derived cell lines. Indeed, ATGL slackened both glucose uptake/utilization and cell proliferation in parallel with increased oxidative metabolism of fatty acids and enhanced mitochondria capacity. We ascribed these ATGL-downstream events to the activity of the tumor-suppressor p53, whose protein levels-but not transcript-were upregulated upon ATGL overexpression. The role of p53 was further assessed by abrogation of the ATGL-mediated effects upon p53 silencing or in p53-null hepatocarcinoma Hep3B cells. Furthermore, we provided insights on the molecular mechanisms governed by ATGL in HCC cells, identifying a new PPAR-α/p300 axis responsible for p53 acetylation/accumulation. Finally, we highlighted that ATGL levels confer different susceptibility of HCC cells to common therapeutic drugs, with ATGL overexpressing cells being more resistant to glycolysis inhibitors (e.g., 2-deoxyglucose and 3-bromopyruvate), compared to genotoxic compounds. Collectively, our data provide evidence for a previously uncovered tumor-suppressor function of ATGL in HCC, with the outlined molecular mechanisms shedding light on new potential targets for anticancer therapy.


Assuntos
Carcinoma Hepatocelular/genética , Proteína p300 Associada a E1A/metabolismo , Glicólise/genética , Lipase/genética , Neoplasias Hepáticas/genética , PPAR alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Lipase/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/genética , Transfecção , Células Tumorais Cultivadas , Regulação para Cima/genética
14.
J Microsc Ultrastruct ; 7(3): 136-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31548925

RESUMO

BACKGROUND: In this study we aimed to develop a new in vivo bioluminescence-based tool to monitor and to quantify colon cancer (CC) liver metastasis development. METHODS: HCT 116 cells were transducted with pLenti6/V5-DEST-fLuc for constitutive expression of firefly luciferase. Infection was monitored analyzing endogenous bioluminescence using the IVIS Lumina II In vivo Imaging System and a positive clone constitutively expressing luciferase (HCT 116-fLuc) was isolated. HCT 116-fLuc cells were left untreated or treated with 1 µM GDC-0449, a Hedgehog pharmacological inhibitor. Moreover, 1 x 106 HCT 116-fLuc cells were implanted via intra-splenic injection in nude mice. Bioluminescence was analyzed in these mice every 7 days for 5 weeks. After that, mice were sacrificed and bioluminescence was analyzed on explanted livers. RESULTS: We found that in vitro bioluminescence signal was significantly reduced when HCT 116-fLuc cells were treated with GDC-0449. Regarding in vivo data, bioluminescence sources consistent with hepatic anatomical localization were detected after 21 days from HCT 116-fLuc intrasplenic injection and progressively increased until the sacrifice. The presence of liver metastasis was further confirmed by ex-vivo bioluminescence analysis of explanted livers. CONCLUSIONS: Our in vitro results suggest that inhibition of Hedgehog pathway may hamper CC cell proliferation and impel for further studies. Regarding in vivo data, we set-up a strategy for liver metastasis visualization, that may allow follow-up and quantification of the entire metastatic process. This cost-effective technique would reduce experimental variability, as well as the number of sacrificed animals.

15.
Cancer Immunol Res ; 6(8): 941-952, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30018041

RESUMO

In this study, we investigated the role of the Wnt/ß-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and ß-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4+ or CD8+ T cells. The majority of these T cells expressed a dysfunctional effector memory Eomes+T-bet-phenotype that we defined as partially exhausted, because they performed effector functions (in terms of interferon-γ and tumor necrosis factor-α production, as well as CD107a mobilization) despite their PD-1 expression. Wnt3a/ß-catenin signaling in T naïve cells in vitro recapitulated the T-cell setting in vivo Indeed, the differentiation of cultured T naïve cells was arrested, producing cells that resembled the EomeshighT-betlowß-cateninhigh T cells with moderate effector functions that infiltrated tumor and nontumor areas. Wnt3a blockade improved the capacity of T naïve cells to differentiate into effector cells in vitro However, Wnt3a blockade did not affect the function and phenotype of differentiated, partially exhausted, tumor-infiltrating T cells ex vivo Taken together, our data suggest that Wnt3a blockade halts the capacity of Wnt/ß-catenin signaling to inhibit the differentiation of T naïve cells, but it does not restore the dysfunction of differentiated T cells, in the tumor setting. Cancer Immunol Res; 6(8); 941-52. ©2018 AACR.


Assuntos
Carcinoma Hepatocelular/imunologia , Neoplasias Colorretais/imunologia , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Via de Sinalização Wnt/imunologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Proteína Wnt3A/imunologia , beta Catenina/metabolismo
18.
Int Surg ; 100(5): 805-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26011198

RESUMO

Leiomyomas (LMs) may appear throughout the entire gastrointestinal tract but are rarely seen in the colon-rectum and only 5 of those measured greater than 15 cm in diameter. Pain and palpable abdominal mass are the most common symptoms. Surgical resection is the treatment of choice for most LMs. We here describe a case of a 46-year-old woman who presented with a 3-month history of abdominal pain associated with worsening constipation and abdominal distension. A pelvic solid, polylobulate, left-sided mass was noted on examination. Preoperative findings revealed a dishomogeneous sigmoid mass with calcified spots compressing small intestine and bladder. At laparotomy, a large polylobulate and well-circumscribed mass arising from the descending colon mesentery and displacing small intestine, uterus, and ovaries. A segmental colon resection was performed. An extraluminal 18- × 12- × 5-cm paucicellular sigmoid colon leiomyoma was histologically diagnosed. Our case is one of the few giant (>15 cm) sigmoid colon LMs reported in the literature. Although rare and benign in nature, LMs of the colon can cause life-threatening complications that could require emergency treatment and they should be included in the differential diagnosis of large abdominopelvic masses. Follow-up after surgery is necessary for tumors with any atypia or mitotic activity.


Assuntos
Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Leiomioma/diagnóstico , Leiomioma/cirurgia , Colectomia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade
20.
Int J Surg Pathol ; 22(2): 182-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24008439

RESUMO

Pure adenocarcinomas of the urothelium are very rare and their location in the pelvis is uncommon. Although their pathogenesis is not well defined, adenocarcinomas are likely to originate from neoplastic transformation of the glandular cells of the urothelial intestinal metaplasia usually arising in response to chronic irritating stimuli, such as long-duration inflammation, urolithiasis, and hydronephrosis. We report a case of an 81-year-old woman who underwent right nephrectomy for relapsing renal abscess due to a staghorn calculus. Histological examination disclosed an infiltrating adenocarcinoma arising from a tubulovillous adenoma with the surrounding pelvic mucosa showing a sequence of intestinal metaplasia, low- and high-grade villous adenoma, and invasive adenocarcinoma, supporting the hypothesis of cancer progression due to chronic inflammation from the urothelium through the metaplasia step.


Assuntos
Abscesso/patologia , Adenocarcinoma/patologia , Intestinos/patologia , Nefropatias/patologia , Neoplasias Renais/patologia , Pelve Renal/patologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperplasia
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