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1.
Surg Innov ; 27(1): 11-18, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31394981

RESUMO

Introduction. Despite the widespread use of the robotic technology, only a few studies with small sample sizes report its application to pancreatic diseases treatment. Our aim is to present the results of a multicenter study on the safety and feasibility of robot-assisted distal pancreatectomy (RDP). Materials and Methods. All RDPs for benign, borderline, and malignant diseases performed in 5 referral centers from 2008 to 2016 were included. Perioperative outcomes were evaluated. Results. Two hundred thirty-six patients were included. Spleen preservation was performed in 114 cases (48.3%). Operative time was 277.8 ± 93.6 minutes. Progressive improvement in operative time was observed over the study period. Conversion rate was 6.3%. Morbidity occurred in 102 cases (43.2%), mainly due to grade A fistulas. Reoperation was required in 10 patients. Postoperatively, 2 patients died of sepsis due to a grade C fistula. Hospital readmission was necessary in 11 cases. A R0 resection was always achieved, with a mean number of 16.2 ± 15 harvested lymph nodes. Conclusion. To our knowledge, this is one of the largest RDP series. Safety and feasibility including the low conversion rate, the high spleen preservation rate, the adequate operative time, and the acceptable morbidity and mortality rates confirm the validity of this technique. Appropriate oncological outcomes have been also obtained.


Assuntos
Pancreatectomia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Baço/cirurgia
2.
BMC Cancer ; 19(1): 452, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088413

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is not a clinically homogeneous disease, but subsets of patients with distinct prognosis and response to therapy can be identified by genome-wide analyses. Mutations in major PDAC driver genes were associated with poor survival. By bioinformatics analysis, we identified protocadherins among the most frequently mutated genes in PDAC suggesting an important role of these genes in the biology of this tumor. Promoter methylation of protocadherins has been suggested as a prognostic marker in different tumors, but in PDAC this epigenetic modification has not been extensively studied. Thus, we evaluated whether promoter methylation of three frequently mutated protocadherins, PCDHAC2, PCDHGC5 and PCDH10 could be used as survival predictors in PDAC patients. METHODS: DNA extracted from 23 PDACs and adjacent non-neoplastic pancreatic tissues were bisulfite treated. Combined Bisulfite Restriction Analysis (COBRA) coupled to denaturing high-performance liquid chromatography (dHPLC) detection and bisulfite genomic sequencing (BGS) were used to determine the presence of methylated CpG dinucleotides in the promoter amplicons analyzed. RESULTS: In an exploratory analysis, two protocadherins showed the same pattern of CpG methylation in PDAC and adjacent non-neoplastic pancreatic tissues: lack of methylation for PCDHAC2, complete methylation for PCDHGC5. Conversely, the third protocadherin analyzed, PCDH10, showed a variable degree of CpG methylation in PDAC and absence of methylation in adjacent non-neoplastic pancreatic tissues. At Kaplan-Meier analysis, high levels of PCDH10 methylation defined according to the receiver operating characteristic (ROC) curve analysis were significantly associated with worse progression-free survival (PFS) rates (P = 0.008), but not with overall survival (OS). High levels of PCDH10 methylation were a prognostic factor influencing PFS (HR = 4.0: 95% CI, 1.3-12.3; P = 0.016), but not the OS. CONCLUSIONS: In this study, we show for the first time that the methylation status of PCDH10 can predict prognosis in PDAC patients with a significant impact on the outcome in terms of progression-free survival. High levels of PCDH10 promoter methylation could be useful to identify patients at high risk of disease progression, contributing to a more accurate stratification of PDAC patients for personalized clinical management.


Assuntos
Caderinas/genética , Carcinoma Ductal Pancreático/genética , Metilação de DNA , Neoplasias Pancreáticas/genética , Adulto , Idoso , Ilhas de CpG , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Protocaderinas , Curva ROC , Análise de Sequência de DNA , Análise de Sobrevida
3.
Langenbecks Arch Surg ; 403(6): 769-775, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30083837

RESUMO

BACKGROUND: Splenic flexure (SF) cancer is not a common condition and its treatment is still under discussion. Although laparoscopic surgery is well accepted for the treatment of colon cancer at any stage, complete mesocolon excision (CME) with selective vascular ligation using the laparoscopic approach for SF cancer remains technically demanding and represents a real challenge for surgeons. METHODS: We present a single-institution experience of laparoscopic CME for SF cancer. Intra-operative, pathologic, and post-operative data of patients who underwent laparoscopic SF resection were reviewed to assess the technical feasibility and oncologic safety. Technical features, histopathology, morbidity, and mortality were evaluated. RESULTS: From February 2015 to October 2017, a minimally invasive approach was proposed to 17 patients (M/F 14/3) affected by splenic flexure cancer. In all patients, the procedure was completed by laparoscopy. The anastomosis was completed intra-corporeally in 89% of cases. The distal margin was 3.1 ± 2.6 cm and the proximal margin was 6.5 ± 3.3 cm from the tumor site. The number of mean harvested nodes was 13.9 ± 7. The mean operative time was 215.5 ± 65 min, and blood loss was 80 ± 27. In one case, a laparoscopic partial gastrectomy was associated due to tumor invasion. The mean post-operative stay was 6.7 ± 3.3 days. Readmission was necessary for two patients. No major morbidity was recorded. CONCLUSIONS: Despite the wide spread and increasing confidence in laparoscopic colectomy, SF resection remains one of the most challenging procedures in colorectal surgery with a complex learning curve. SF resection with CME and CVL is feasible and safe for the treatment of early-stage and locally advanced SF cancer.


Assuntos
Colectomia/métodos , Colo Transverso/patologia , Colo Transverso/cirurgia , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Mesocolo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/métodos , Estudos de Coortes , Colectomia/mortalidade , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Humanos , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Segurança do Paciente/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
4.
Langenbecks Arch Surg ; 402(3): 475-479, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27987098

RESUMO

PURPOSE: The growing pressure to rationalize costs in the healthcare system demands the development of new healthcare models aimed at allowing patients to receive the best treatment, without ignoring the rising costs. METHODS: In the Healthcare Unit 2 located in the Abruzzo region in Italy, a new model of intensified care surgical department was designed in January 2013. The department was based on the selection of the degree of patient disease. Patients requiring a medium-low degree surgery were treated in the peripheral unit, in the Ortona hospital, while more complex surgical procedures, most cancer cases (including stomach, liver, pancreas, colon-rectum or multi-organ resections), were performed in the central unit in the Chieti hospital. RESULTS: The value of production at the peripheral unit, in Ortona, increased by 299.4% along with an increase in discharges of 112.6%, with an average DRG weight from 1.02 to 1.45. At the central unit, in Chieti, the average DRG weight produced was 3.328. In relation to quality assessment, pancreatic surgery morbidity was 27.0% and mortality was 1.7 % due to resection and 2.2% for other causes. Likewise, for colon-rectal surgery, a global morbidity of 35.0% and anastomotic leakage of 3.9% was seen. CONCLUSIONS: The 24-month preliminary results show that new models of intensified care surgical departments can be created. In addition, results clearly show that such model significantly improves both services and surgical results. This original model allows optimal use of resources favouring both service quality and patient satisfaction.


Assuntos
Cuidados Críticos/organização & administração , Atenção à Saúde/organização & administração , Qualidade da Assistência à Saúde , Centro Cirúrgico Hospitalar/organização & administração , Hospitalização , Humanos , Itália , Seleção de Pacientes
5.
Carcinogenesis ; 37(10): 957-64, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27497070

RESUMO

Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10(-5)) the association between 30 genomic regions and PDAC OS. With the aim to highlight the true associations within these regions, we analyzed 44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722 PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We observed statistically significant associations for five of the selected regions. One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio (HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes for the minor allele] and one in the last intron of the RUNX2 gene on chromosome 6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are of particular relevance. These loci do not coincide with those that showed the strongest associations in the previous GWAS. In silico analysis strongly suggested a possible mechanistic link between these two SNPs and pancreatic cancer survival. Functional studies are warranted to confirm the link between these genes (or other genes mapping in those regions) and PDAC prognosis in order to understand whether these variants may have the potential to impact treatment decisions and design of clinical trials.


Assuntos
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Estudo de Associação Genômica Ampla , alfa Catenina/genética , Adenocarcinoma/patologia , Idoso , Carcinoma Ductal Pancreático/patologia , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Prognóstico
6.
Biochim Biophys Acta ; 1833(8): 1853-65, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23583560

RESUMO

Colorectal carcinogenesis relies on loss of homeostasic mechanisms regulating cell proliferation, differentiation and survival. These cell processes have been reported to be influenced independently by transcription factors activated downstream of the Wnt pathway, such as SOX9 and ß-catenin, and by the nuclear receptor PPARγ. The purpose of this study was to explore the expression levels and functional link between SOX9, ß-catenin and PPARγ in the pathogenesis of colorectal cancer (CRC). We evaluated SOX9, ß-catenin and PPARγ expression levels on human CRC specimens by qPCR and immunoblot detection. We tested the hypothesis that PPARγ activation might affect SOX9 and ß-catenin expression using four colon cancer cell lines (CaCo2, SW480, HCT116, and HT29 cells). In CRC tissues SOX9 resulted up-regulated at both mRNA and protein levels when compared to matched normal mucosa, ß-catenin resulted up-regulated at protein levels, while PPARG mRNA and PPARγ protein levels were down-regulated. A significant relationship was observed between high PPARG and SOX9 expression levels in the tumor tissue and female gender (p=0.005 and p=0.04, respectively), and between high SOX9 expression in the tumor tissue and age (p=0.04) and microsatellite instability (MSI), in particular with MSI-H (p=0.0002). Moreover, treatment with the synthetic PPARγ ligand rosiglitazone induced different changes of SOX9 and ß-catenin expression and subcellular localization in the colon cancer cell lines examined. In conclusion, SOX9, ß-catenin and PPARγ expression levels are deregulated in the CRC tissue, and in colon cancer cell lines ligand-dependent PPARγ activation unevenly influences SOX9 and ß-catenin expression and subcellular localization, suggesting a variable mechanistic role in colon carcinogenesis.


Assuntos
Neoplasias Colorretais/metabolismo , PPAR gama/metabolismo , Fatores de Transcrição SOX9/metabolismo , beta Catenina/metabolismo , Idoso , Células CACO-2 , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Masculino , PPAR gama/genética , Fatores de Transcrição SOX9/genética , Regulação para Cima , beta Catenina/genética
7.
J Transl Med ; 12: 248, 2014 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-25199538

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. METHODS: mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used. RESULTS: RECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk. CONCLUSION: hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Idoso , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Estudos de Coortes , Desoxicitidina/uso terapêutico , Progressão da Doença , Transportador Equilibrativo 1 de Nucleosídeo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , RNA Mensageiro/genética , Taxa de Sobrevida , Fator de Transcrição CHOP/genética , Gencitabina
8.
Langenbecks Arch Surg ; 399(5): 649-57, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24682374

RESUMO

PURPOSE: Controversy prevails on the impact of preoperative biliary drainage (PBD) on postoperative complications and clinical outcome of pancreatic cancer. We determined whether PBD is associated with increased morbidity and mortality rates after pancreaticoduodenectomy. METHODS: A total of 131 consecutive patients who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were included in this study. Overall, 57 % of jaundiced patients underwent PBD, while 43 % were not drained. The impact of PBD on postoperative morbidity and mortality was evaluated by means of logistic regression analysis. The Kaplan-Meier method was applied to determine the effect of PBD on survival of patients with malignant lesions. RESULTS: Mortality and morbidity rate was 3 % and 54.6 %, respectively. PBD was demonstrated to be the unique predictor of complications (odds ration [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The jaundiced patients who were drained exhibited high frequencies of wound infection (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p < 0.001). In addition, an increased frequency of pancreatic fistula emerged among drained patients compared to those who were not drained (p = 0.036). PBD did not affect survival of patient with malignant lesions. CONCLUSIONS: With the exception of the classical indications, PBD should be carefully evaluated in patients with resectable pancreatic cancer.


Assuntos
Drenagem/métodos , Icterícia Obstrutiva/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Ductos Biliares/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Intervalos de Confiança , Drenagem/efeitos adversos , Feminino , Humanos , Icterícia Obstrutiva/mortalidade , Icterícia Obstrutiva/patologia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Cuidados Pré-Operatórios/métodos , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Radiol Med ; 119(5): 334-42, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24619824

RESUMO

PURPOSE: A tumour score for venous invasion in patients with pancreatic adenocarcinoma was evaluated by means of computed tomography (CT), in order to improve the assessment of medical treatment and clinical outcome with special attention to borderline resectable disease. MATERIALS AND METHODS: Fifty-six consecutive patients who underwent curative surgical resection for pancreatic cancer were analysed. On the basis of CT criteria, tumour involvement of the portal vein (PV) and superior mesenteric vein (SMV) was graded according to an adapted 4-point scale: score 1, definite absence of invasion; score 2, probable absence of invasion; score 3, probable presence of invasion; score 4, definite presence of invasion. Correlations between the venous infiltration scores and the patients' clinical features were also evaluated. RESULTS: After radiological evaluation of PV and SMV grades of infiltration, 21/56 (37 %) and 37/56 (66 %) patients, respectively, were found to have borderline resectable disease. The 4-point scale achieved a sensitivity of 80 %, a specificity of 96 % and an accuracy of 93 % in the evaluation of the PV, and a sensitivity of 100 %, a specificity of 94 % and an accuracy of 95 % in the evaluation of the SMV. Analysis of the distribution of clinical characteristics by PV and SMV infiltration showed that both scores correlated with the presence of distal metastasis (p = 0.016 and p = 0.028, respectively), and resection margins status (p = 0.015 and p = 0.006, respectively). CONCLUSIONS: This adapted tumour score is reliable for assessing venous invasion and might improve preoperative staging in patients with borderline resectable pancreatic cancer.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Neoplasias Pancreáticas/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade
10.
Minerva Surg ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916536

RESUMO

BACKGROUND: Routine splenic flexure mobilization (SFM) during left hemicolectomy and high anterior rectal resection guarantees a well perfused and tension-free anastomosis, respecting current oncological criteria. According to the recent literature, only 70% of laparoscopic colorectal surgeons considered routine SFM mandatory. Because of its difficulty, SFM increases morbidity including surrounding organs injuries. The goal of the study is to report our experience in avoiding routine SFM during colorectal resection compared to the current surgical state of art. METHODS: Data were collected retrospectively on elective left hemicolectomy without routine SFM performed in our unit between January 2015 to April 2020. Patients were recruited according to diagnosis, histopathology, operative time, ASA score, post-operative morbidity and mortality. RESULTS: Seventy-five oncological patients, underwent to surgery without SFM. The other 13 patients underwent to SFM due to technical issues. The mean operative time was 160.2±44.7 mins, significantly shorter than in patients whose SFM occurred (210.3 min). The morbidity rate was 1%, reintervention occurred in one patient. Eighteen-month median follow-up morbidity was 11% while mortality was 3%. Recurrence rate was of about 5%. CONCLUSIONS: As results from study data analysis, left colectomy can be conducted safely in both laparoscopic and laparotomic approach without SFM in selected cases. As reported in a recent meta-analysis, benefits of avoiding SFM concern reduced operative time without compromising postoperative outcome and respecting oncological criteria, as emerged by our results. Colorectal resection without SFM when is feasible, improves surgical approach reducing technical difficulties and avoiding splenic injuries.

11.
Front Cardiovasc Med ; 11: 1301538, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638881

RESUMO

A 74-year-old man with advanced heart failure was admitted to the hospital with a diagnosis of colorectal cancer, and he underwent surgery. To maintain stable hemodynamics, the Impella CP device was used. The patient was weaned from the device shortly after surgery, and he had an uneventful postoperative course. This case may pave the way for non-procrastinating surgery in patients with poorly stable hemodynamics.

12.
Am J Pathol ; 181(5): 1524-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22944597

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers, being the fourth leading cause of cancer-related deaths. Long-term survival reaching 15% is achieved in less than 5% of patients who undergo surgery, and median survival is only 6 months in those with inoperable lesions. A deeper understanding of PDAC biologic characteristics as well as novel prognostic markers are therefore required to improve outcomes. Herein we report that BAG3, a protein with recognized anti-apoptotic activity, was expressed in 346 PDACs analyzed, but was not expressed in the surrounding nonneoplastic tissue. In a cohort of 66 patients who underwent radical resection (R0), survival was significantly shorter in patients with high BAG3 expression (median, 12 months) than in those with low BAG3 expression (median, 23 months) (P = 0.001). Furthermore, we report that BAG3 expression in PDAC-derived cell lines protects from apoptosis and confers resistance to gemcitabine, offering a partial explanation for the survival data. Our results indicate that BAG3 has a relevant role in PDAC biology, and suggest that BAG3 expression level might be a potential marker for prediction of patient outcome.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Apoptose , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Adenocarcinoma/tratamento farmacológico , Idoso , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/tratamento farmacológico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Gencitabina
13.
Pancreatology ; 12(5): 395-401, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23127526

RESUMO

Pancreatic cancer is the result of distinctive genetic and epigenetic disturbances. This multistep process is in part well-defined and includes alterations in oncogenes and suppressor genes that control proliferation, apoptosis, angiogenesis, invasion and cell migration. Cathepsins are proteolytic enzymes and represent potential therapeutic targets in human tumors. Cathepsins predominantly function as endopeptidases within endolysosomal vesicles of normal cells and they are involved in physiological processes such as protein turnover, differentiation and apoptosis. In various types of malignancies, cathepsins have been associated with tumor progression and metastasis. Growing evidence and direct proofs suggest that cathepsins are highly up-regulated in pancreatic cancer and contribute to the development and progression of the cancer phenotype. In this review, the role of cathepsins in pancreatic cancer tumorigenesis is reported and discussed. Some critical aspects will be underlined such as specificity of cathepsin activity in pancreatic cancer and in its precursor lesions; the genetic perturbation and the intracellular signaling pathway activated by cathepsins as reported in preclinical models and in human tissues; the preliminary results and the oncological effects of cathepsin inhibitors currently tested on pancreatic cancer cells; the role of combined therapy based on chemotherapeutic agents and cathepsin inhibition. Although mounting evidences indicate that cysteine cathepsins are potential therapeutic targets in pancreatic cancer, as suggested by their functional role in controlling invasiveness and metastasis, it remains to be seen whether the promising benefits of pharmacological inhibitors observed in preclinical study might be translated to the current clinical practice.


Assuntos
Catepsinas/fisiologia , Inibidores de Cisteína Proteinase/uso terapêutico , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/etiologia , Animais , Antineoplásicos/farmacologia , Catepsinas/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neovascularização Patológica/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos
14.
Cancers (Basel) ; 14(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36230671

RESUMO

Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide. Identification of novel tumor biomarkers is highly advocated in PC to optimize personalized treatment algorithms. Blood-circulating extracellular vesicles hold promise for liquid biopsy application in cancer. We used an optimized flow cytometry protocol to study leukocyte-derived EVs (CD45+) and PD-L1+ EVs in blood from 56 pancreatic cancer patients and 48 healthy controls (HCs). Our results show that PC patients presented higher blood levels of total EVs (p = 0.0003), leukocyte-derived EVs (LEVs) (p = 0.001) and PD-L1+ EVs (p = 0.01), as compared with HCs. Interestingly, a blood concentration of LEVs at baseline was independently associated with improved overall survival in patients with borderline resectable or primary unresectable PC (HR = 0.17; 95% CI 0.04-0.79; p = 0.02). Additionally, increased blood-based LEVs were independently correlated with prolonged progression-free survival (HR = 0.10; 95% CI 0.01-0.82; p = 0.03) and significantly associated with higher disease control rate (p = 0.02) in patients with advanced PC receiving standard chemotherapy. Notably, a strong correlation between a decrease in blood LEVs concentration during chemotherapy and disease control was observed (p = 0.005). These intriguing findings point to the potential of LEVs as novel blood-based EV biomarkers for improved personalized medicine in patients affected by PC.

15.
Langenbecks Arch Surg ; 396(3): 345-51, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20703500

RESUMO

OBJECTIVE: The objective of this study is to evaluate the impact of a fast-track protocol in a high-volume center for patients with pancreatic disorders. BACKGROUND: The concept of fast-track surgery allowing accelerated postoperative recovery is accepted in colorectal surgery, but efficacy data are only preliminary for patients undergoing major pancreatic surgery. We aimed to evaluate the impact of a modified fast-track protocol in a high-volume center for patients with pancreatic disorders. METHODS: Between February 2005 and January 2010, 145 subjects had resective pancreatic surgery and were enrolled in the program. Essential features of the program were no preanaesthetic medication, upper and lower air-warming device, avoidance of excessive i.v. fluids perioperatively, effective control of pain, early reinstitution of oral feeding, and immediate mobilization and restoration of bowel function following surgery. Outcome measures were postoperative complications such as pancreatic fistula, delayed gastric emptying, biliary leak, intra-abdominal abscess, post-pancreatectomy hemorrhage, acute pancreatitis, wound infection, 30-day mortality, postoperative hospital stay, and readmission rates. RESULTS: On average, patients were discharged on postoperative day 10 (range 6-69), with a 30-day readmission rate of 6.2%. Percentage of patients with at least one complication was 38.6%. Pancreatic anastomotic leakage occurred in seven of 101 pancreatico-jejunostomies, and biliary leak in three of 109 biliary jejunostomies. Postoperative hemorrhage occurred in ten (6.9%) patients and wound infection in nine (6.2%) cases. In-hospital mortality was 2.7%. Fast-track parameters, such as normal food and first stool, correlated significantly with early discharge (<0.05). At multivariate analysis, lack of jaundice, and resumption of normal diet by the 5th postoperative day were independent factors of early discharge. CONCLUSION: Fast-track programs are feasible, easy, and also applicable for patients undergoing a major surgery such as pancreatic resection.


Assuntos
Procedimentos Clínicos/organização & administração , Tempo de Internação/tendências , Pancreatectomia/métodos , Pancreatopatias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/mortalidade , Pancreatopatias/mortalidade , Pancreatopatias/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Alta do Paciente/tendências , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Cuidados Pré-Operatórios/métodos , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Fatores de Tempo
16.
Cancers (Basel) ; 13(24)2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34944856

RESUMO

BACKGROUND: colorectal cancer (CRC) has a multifactorial etiology which comprises microbiota, genetic predisposition, diet, environmental factors, and last but not least, a substantial contribution by inflammation. The aim of this study is to conduct a systematic review of the literature regarding the strong link between inflammation and colorectal cancer. METHODS: A systematic review of the literature on PubMed (Medline), Scopus, Cochrane and EMBase databases was performed, following the PRISMA 2020 guidelines. Each paper was reviewed by two groups of researchers in a single-blind format by using a pre-planned Microsoft© Excel® grid. RESULTS: Using automated research filters, 14,566 studies were included, but 1% was found significant by the reviewers. Seventy pathways of inflammation were described in the sequence of inflammation-carcinogenesis, and anti-tumorigenic molecules were also found. CONCLUSION: several studies suggest a strong role of inflammation in the tumorigenesis of colorectal cancer through different pathways: this may have a diagnostic and clinical role and also therapeutic purpose in preventing carcinogenesis by treating inflammation. In vitro tests support this theory, even if many other clinical trials are necessary. The present paper was registered in the OpenScience Framework registry (Identifier: DOI 10.17605/OSF.IO/2KG7T).

17.
Updates Surg ; 73(6): 2215-2223, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33387169

RESUMO

Trans-duodenal surgical ampullectomy (TSA) was first described in 1899. Nowadays its role in ampullary tumor surgery is still a matter of debate and requires a multidisciplinary approach. The aim of this study is to evaluate the results of TSA as a curative treatment for benign and selected malignant tumors arising from the ampulla in a single-institution experience. Sixteen patients with periampullary tumors that underwent TSA in our surgical units between January 2012 and January 2017 were included in the study. Patient demographic characteristics, pre or postoperative endoscopic interventions, operative procedures, postoperative morbidity and mortality, hospitalization, follow-up time, and quality of life questionnaire were analyzed. Mean operative time was 238.5 min (range 180-390), mean tumor size was 2.3 cm (range 1.5-3.9). The microscopic surgical outcome was R0 for 14 patients. The most frequent findings in terms of histological type were high-grade dysplasia/pTis (43.7%), low-grade dysplasia in 37.5% patients, invasive adenocarcinoma in 2 cases (12.5%), chronic inflammation in 1 case (6.3%). The readmission rate was 18.8% (3/16) and in 2 cases (12.5%) relaparotomy was required. The cumulative median duration of follow-up was 50 months (range 1-96). 90-days mortality was 6.2%. Mean hospital stay was 12 days (range 8-60). Our results confirm that TSA offers good results in terms of morbidity and mortality; still, it remains a challenging procedure that requires particular surgical experience and operative skills. A pre-operative planning in a multidisciplinary board should be carried out prior to the procedure.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Humanos , Pancreaticoduodenectomia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
18.
Asian J Endosc Surg ; 14(3): 496-503, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33264814

RESUMO

BACKGROUND: Although laparoscopic cholecystectomy (LC) is the gold standard for symptomatic gallbladder disease, a single-incision approach may be a new challenge in order to achieve minimization of surgical trauma. Single-site robotic cholecystectomy (SSRC) is able to offset the ergonomic limitation of laparoscopic single-site cholecystectomy and improves cosmesis. METHODS: We present a single-institution initial experience of SSRC for cholecystolithiasis. Intra-operative and post-operative data of patients were reviewed to assess the technical feasibility and cosmetic outcome. RESULTS: We evaluated a series of 27 consecutive patients retrospectively analyzed and prospectively collected who underwent SSRC. One patient was excluded from the final analysis because they converted to open procedure. The female/male ratio was 17/9, with mean age of 48 ± 12 years. The body mass index mean value was 26.0 ± 4.2. The mean operative time was 99.6 ± 21.5 minutes. No intra- or post-operative complications and readmissions were recorded. At 12 months follow up, every patient received the Body Image Questionnaire (BIQ) and a Photo Series Questionnaire. We recorded three patients (11.5%) with post-operative incisional hernia. Scores of the BIQ subscale for body image perception were 6 ± 1.2, while the scores of scar cosmesis were 21.1 ± 3.0. A statistically significant improvement in scar self-rating from T0 to T1 (P < .01) was found. CONCLUSION: In our initial experience SSRC may be preferred to treat patients with higher needs in terms of cosmesis and body image perception. Lower costs for rent, maintenance and consumables may allow the spread of robotic surgery also for singe site cholecystectomy.


Assuntos
Colecistectomia , Colecistolitíase/cirurgia , Procedimentos Cirúrgicos Robóticos , Adulto , Colecistectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
19.
Surg Res Pract ; 2021: 4547537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553574

RESUMO

BACKGROUND: Laparoscopic reversal of Hartmann's procedure (LHR) offers reduced morbidity compared with open Hartmann's reversal (OHR). The aim of this study is to compare the outcome of laparoscopic versus open Hartmann reversal. MATERIALS AND METHODS: Thirty-four patients who underwent Hartmann reversal between January 2017 and July 2019 were evaluated. Patients underwent either LHR (n = 17) or OHR (n = 17). Variables such as numbers of patients, patient's age, sex, body mass index (BMI), comorbidities, ASA (American Society of Anesthesiology) score, indication for previous open sigmoid resection, mean operation time, rate of conversion to open surgery, length of hospital stay, mortality, and morbidity were retrospectively evaluated. RESULTS: The two groups of patients were homogeneous for gender, age, body mass index, cause of primary surgery, time to reversal, and comorbidities. In 97% of the cases, HP was done by open surgery. Our data revealed no difference in mean operation time (LHR: 180.5 ± 35.1 vs. OHR: 225.2 ± 48.4) and morbidity rate, although, in OHR group, there were more severe complications. Less intraoperative blood loss (LHR: 100 ± 40 mL vs. OHR: 450 ± 125 mL; p value <0.001), shorter time to flatus (LHR: 2.4 days vs. OHR: 3.6 days; p value <0.021), and shorter hospitalization (LHR: 4.4 vs. OHR: 11.2 days; p value <0.001) were observed in the LHR group. Mortality rate was null in both groups. Discussion. LHR is feasible and safe even for patients who received a primary open Hartmann's procedure. We suggest careful patient's selection allowing LHR procedures to highly skilled laparoscopy surgeons.

20.
Sci Rep ; 11(1): 5379, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686147

RESUMO

Neoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the "tumor core" (TC) and the "tumor border" (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based "clinical-radiomic" machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10-5). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.


Assuntos
Aprendizado de Máquina , Imageamento por Ressonância Magnética , Modelos Biológicos , Terapia Neoadjuvante , Neoplasias Retais , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia
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