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1.
Eur J Surg Oncol ; 50(9): 108526, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39024693

RESUMO

INTRODUCTION: Although the management of gynecological cancers recurrences may be challenging, due to the heterogeneity of recurrent disease, the aim of this work is to present a descriptive analysis of gynecological malignancies recurrences in our institution treated by robotic approach. MATERIALS AND METHODS: We performed a retrospective review and analysis of data of patients who underwent robotic surgery for recurrent gynecological malignancies at Catholic University of the Sacred Hearth, Rome, from January 2013 to January 2024. RESULTS: A total of 54 patients underwent successful robotic cytoreductive surgery. The median age was 63 years; the median BMI was 33 kg/m2 and most of the patients (59 %) were obese. In 12 cases (22 %) the relapse presented was the second or third relapse. The most frequent patterns of recurrence were represented by lymph nodes (41 %), followed by peritoneal (26 %), pelvic (22 %) and parenchymal (11 %). In all patients complete cytoreduction was achieved. In 29 patients (54 %) the surgical field was previous treated. The median operative time and estimated blood loss were, respectively, 270 min and 100 ml. There were 2 intraoperative complications, managed endoscopically; 10 early postoperative complications, and 3 late postoperative complications. The 2-year progression-free-survival and overall survival were, respectively, 39.8 % and 72.3 %. CONCLUSION: Robotic approach in the treatment of recurrent gynecological cancers should be considered in selected patients with oligometastatic disease, in high-volume centers with expert surgeons, particularly in obese patients.

2.
Cancers (Basel) ; 16(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38927889

RESUMO

In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.

3.
Gynecol Oncol ; 187: 98-104, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38749171

RESUMO

OBJECTIVE: The study aimed to characterize intra-and postoperative complications according to a standardized anatomo-surgical classification for ovarian cancer metastases in the liver area. METHODS: Data from all patients with advanced ovarian cancer undergoing primary or secondary surgery with perihepatic liver involvement (May-2016 to May-2022), were retrospectively retrieved and classified according to a standardized anatomo-surgical classification, and clustered into four Classes: Class I "Peritoneal", Class II "Hepatoceliac-lymph-nodes", Class III "Parenchymal" and Class IV Mixed (≥ 2 classes). RESULTS: Data from 615 patients were collected. Intraoperative complications were observed in 15%, and severe postoperative complications in 17.6% of cases. While surgical complexity scores were similar, Class IV had longer operative times, higher blood loss, and a 30.4% intraoperative transfusion rate. Class II showed a higher prevalence of vascular injuries (8%). Classes II and IV were significantly associated with severe postoperative complications. Specific complications varied among classes, such as perihepatic collection and intrahepatic hematoma/abscess in Class III (p = 0.003, p < 0.001, respectively), and pleuric effusion, sepsis, anemia, and "other complications" in Class IV (p = 0.002, p = 0.004, p = 0.03, p = 0.03, respectively). Multivariable analysis identified Class II and IV (Class II: OR 4.991, p = 0.045; Class IV: OR 5.331, p = 0.030), Surgical Complexity Score group 3 (OR:3.922, p = 0.003), and the presence of residual tumor (OR:1.748, p = 0.048) as independent risk factors for severe postoperative complications. CONCLUSIONS: Liver procedures during advanced ovarian cancer surgery are feasible with acceptable complication rates According to the anatomo-surgical classification, metastatic patterns are related to both different surgical outcomes and postoperative complication profiles.

4.
Int J Surg ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38818688

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.

5.
Hepatobiliary Surg Nutr ; 13(2): 241-257, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617496

RESUMO

Background: Economic impact of robotic liver surgery (RLS) is still a debated issue due to the heterogeneity of liver resections considered and the lack of a rigorous methodology. Therefore, the aim of this study is to perform a time-driven activity-based costing (TD-ABC) comparing the costs of RLS, laparoscopic liver surgery (LLS) and open liver surgery (OLS) in the context of complex liver resections and to compare short term perioperative outcomes. Methods: The institutional databases of two Italian high volume hepatobiliary centres were retrospectively reviewed from February 2021 to April 2022. Patients submitted to major hepatectomies or postero-superior liver resections were selected and divided into three groups according to the approach scheduled (RLS, LLS and OLS) and compared. Major contributors of perioperative expenses were calculated using the TD-ABC model and accurately quantifying each unit resource consumed per patient and the time spent performing each activity. A primary intention-to-treat analysis (ITT-A) including conversions in the RLS and LLS groups was performed. Results: Forty-seven RLS, 101 LLS and 124 OLS were collected. LLS and RLS showed reduced blood loss, morbidity, mortality and hospital stay compared with open. A trend towards reduced conversion rate in RLS compared to LLS was registered. Total costs associated with RLS were estimated at €10,637 vs. €9,543 for LLS and vs. €13,960 for OLS. The higher intraoperative costs associated with RLS (+153.3% vs. OLS and +148.2% vs. LLS, P<0.001), primarily related to surgical equipment expenses, were slightly offset by the postoperative savings (-56.0% vs. OLS and -29.4% vs. LLS, P<0.001) resulting from significantly reduced hospital stays. Conclusions: RLS offers economic advantages over OLS, as initial higher costs are offset by better perioperative outcomes. The evolving robotic marketplace is expected to drive down RLS costs, promoting widespread adoption in minimally invasive procedures. Despite its higher costs than LLS, RLS's ability to enhance minimally invasive feasibility makes it a preferred choice for complex cases, reducing the need for conversions.

6.
Updates Surg ; 75(6): 1509-1517, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37580549

RESUMO

Impact of timing of repair on outcomes of patients repaired with Hepp-Couinaud hepatico-jejunostomy (HC-HJ) after bile duct injury (BDI) during cholecystectomy remains debated. This is an observational retrospective study at a tertiary referral hepato-biliary center. HC-HJ was always performed in patients without sepsis or bile leak and with dilated bile ducts. Timing of repair was classified as: early (≤ 2 weeks), intermediate (> 2 weeks, ≤ 6 weeks), and delayed (> 6 weeks). 114 patients underwent HC-HJ between 1994 and 2022: 42.1% underwent previous attempts of repair at referring institutions (Group A) and 57.9% were referred without any attempt of repair before referral (Group B). Overall, a delayed HC-HJ was performed in 78% of patients; intermediate and early repair were performed in 17% and 6%, respectively. In Group B, 10.6% of patients underwent an early, 27.3% an intermediate, and 62.1% a delayed repair. Postoperative mortality was nil. Median follow-up was 106.7 months. Overall primary patency (PP) attainment rate was 94.7%, with a 5- and 10-year actuarial primary patency (APP) of 84.6% and 84%, respectively. Post-repair bile leak was associated with PP loss in the entire population (odds ratio [OR] 9.75, 95% confidence interval [CI] 1.64-57.87, p = 0.012); no correlation of PP loss with timing of repair was noted. Treatment of anastomotic stricture (occurred in 15.3% of patients) was performed with percutaneous treatment, achieving absence of biliary symptoms in 93% and 91% of cases at 5 and 10 years, respectively. BDI can be successfully repaired by HC-HJ regardless of timing when surgery is performed in stable patients with dilated bile ducts and without bile leak.


Assuntos
Ductos Biliares , Colecistectomia Laparoscópica , Humanos , Ductos Biliares/cirurgia , Ductos Biliares/lesões , Jejunostomia , Estudos Retrospectivos , Centros de Atenção Terciária , Colecistectomia/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Resultado do Tratamento
7.
Ann Surg Oncol ; 30(8): 4904-4911, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37149547

RESUMO

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Neoplasias da Vesícula Biliar , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Benchmarking , Linfonodos/patologia , Estudos Retrospectivos
9.
J Gastrointest Surg ; 26(12): 2503-2511, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36127553

RESUMO

BACKGROUND: Recurrence after curative hepatectomy for colorectal liver metastases (CRLM) is common. We sought to determine if number and sites of resections of recurrence after hepatectomy for CRLM impact survival. METHODS: The study included patients who underwent resection of recurrence following complete curative-intent resection of CRLM during 1998-2016 at two academic medical centers in Houston, USA, and Rome, Italy. The survival impacts of number and sites of resections of recurrence were evaluated. Patients with synchronous extrahepatic disease at curative CRLM resection were excluded. RESULTS: Among 2163 patients who underwent curative hepatectomy, 1456 (67.3%) developed a recurrence. Four hundred seventy-eight patients underwent one (322/478; 67.4%) or two or more (156/478; 32.6%) resections of recurrence. The 5-year overall survival (OS) rate was higher in patients with resected than unresected recurrence (70.2% vs. 24.0%; p < 0.001). In patients who underwent only one resection of recurrence, the 5-year OS rate differed by location (lung, 81.6%; liver, 64.3%; other, 54.1%). In patients who underwent two or more resections of recurrence, the 5-year OS rate was similar for liver-only resection (87.5%) and resection of liver and other sites (66.1%) (p = 0.223) and for liver-only resection and other-sites-only resection (80.7%) (p = 0.258); 5-year OS rate by site of first resection of recurrence did not differ between liver (78.5%) and lung (81.8%) (p = 0.502) but was worse for other sites (61.1%) than for lung (p = 0.045). CONCLUSION: When recurrence after initial CRLM resection is resectable, the ability to undergo resection was associated with improved survival and can be considered as an option regardless of the number of recurrence and resection. Sites of resection of recurrence impact survival and should be considered.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Hepatectomia , Neoplasias Hepáticas/secundário , Taxa de Sobrevida , Recidiva Local de Neoplasia/cirurgia , Prognóstico
11.
J Gastrointest Surg ; 26(6): 1205-1212, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35296957

RESUMO

BACKGROUND: Postoperative morbidity remains a significant problem after pancreatico-duodenectomy. The management of pancreatic stump continues to be a challenge, and many technical solutions have been developed over the years. In this study, we report the results obtained with the use of an isolated loop for pancreatico-jejunostomy in patients with soft pancreas and small pancreatic duct diameter. METHODS: Clinical data of patients submitted to pancreatico-duodenectomy in a period of sixteen years (2005-2020) were extracted from a prospective database. Patients with soft pancreas, main duct diameter < 2 mm and reconstruction by pancreatico-jejunostomy on single loop or isolated loop were selected. Primary end-point was the incidence of clinically relevant fistulas in the two groups of patients. Secondary endpoint was the length of postoperative hospital stay. A propensity score matching analysis was used for the statistics. RESULTS: Two hundred and twenty-one patients with the above characteristics were found in the database. One hundred and twelve of these received a single-loop reconstruction and 109 an isolated loop reconstruction. Incidence of clinically relevant fistulas was higher in the first group (41% vs 27%; p = 0.023). Postoperative hospital stay was significantly shorter in the second group (21 days vs 15; p < 0.001). These results were confirmed at the propensity score matching. CONCLUSION: In patients with soft pancreatic texture and small main duct diameter, pancreatico-jejunostomy on isolated loop is associated with a lower incidence of clinically relevant fistulas than after classic reconstruction. The duration of postoperative hospital stay was significantly reduced, with consequent reduction of cost.


Assuntos
Fístula Pancreática , Pancreaticojejunostomia , Humanos , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Fístula Pancreática/epidemiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
12.
Ann Surg Oncol ; 28(13): 8198-8208, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34212254

RESUMO

BACKGROUND: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. METHODS: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. RESULTS: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). CONCLUSION: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/cirurgia , Hepatectomia , Humanos , Fígado , Neoplasias Hepáticas/cirurgia , Sistema de Registros , Estudos Retrospectivos
14.
Updates Surg ; 73(4): 1247-1265, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34089501

RESUMO

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15-25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients' selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/cirurgia , Consenso , Hepatectomia , Humanos , Itália , Neoplasias Hepáticas/cirurgia
15.
Ann Surg Oncol ; 28(5): 2675-2682, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33666814

RESUMO

BACKGROUND: Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. PATIENTS AND METHODS: Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000-2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. RESULTS: Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3-T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49-3.13, P < 0.001], 12-month recurrence-free (HR 3.42, 95% CI 1.88-6.23, P < 0.001), and 24-month recurrence-free (HR 2.71, 95% CI 1.11-6.62, P = 0.029). Of the 125 patients without these risk factors, only 2 had recurrence after 36 months. CONCLUSION: C-RFS improves over time, and only T3-T4 disease remains a risk factor for recurrence at 24 months after OER for GBC. For all recurrence-free survivors after 36 months, the probability of recurrence is similar regardless of T category or disease stage.


Assuntos
Neoplasias da Vesícula Biliar , Colecistectomia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
Sci Rep ; 11(1): 2557, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510179

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA. Our results showed that Metformin inhibited cell proliferation and induced dose- and time-dependent apoptosis of iCCA. The migration and invasion of iCCA cells in an extracellular bio-matrix was also significantly reduced upon treatments. Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells. After 12 days of treatment, a marked decrease of mesenchymal and EMT genes and an increase of epithelial genes were observed. After 2 months of treatment, in order to simulate chronic administration, Cytokeratin-19 positive cells constituted the majority of cell cultures paralleled by decreased Vimentin protein expression. Subcutaneous injection of iCCA cells previously treated with Metformin, in Balb/c-nude mice failed to induce tumour development. In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.


Assuntos
Colangiocarcinoma/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Metformina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteína Forkhead Box O3/metabolismo , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos
17.
Hepatology ; 73(1): 144-159, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32978808

RESUMO

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high cancer stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as a CSC marker in different gastroenterological solid tumors. Our aim was to evaluate in vitro the expression and the biological function of DCLK1 in intrahepatic CCA (iCCA) and perihilar CCA (pCCA). APPROACH AND RESULTS: Specimens surgically resected of human CCA were enzymatically digested, submitted to immunosorting for specific CSC markers (LGR5 [leucine-rich repeat-containing G protein-coupled receptor], CD [clusters of differentiation] 90, EpCAM [epithelial cell adhesion molecule], CD133, and CD13), and primary cell cultures were prepared. DCLK1 expression was analyzed in CCA cell cultures by real-time quantitative PCR, western blot, and immunofluorescence. Functional studies have been performed by evaluating the effects of selective DCLK1 inhibitor (LRRK2-IN-1) on cell proliferation (MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, cell population doubling time), apoptosis, and colony formation capacity. DCLK1 was investigated in situ by immunohistochemistry and real-time quantitative PCR. DCLK1 serum concentration was analyzed by enzyme-linked immunosorbent assay. We describe DCLK1 in CCA with an increased gene and protein DCLK1 expression in pCCALGR5+ and in iCCACD133+ cells compared with unsorted cells. LRRK2-IN-1 showed an anti-proliferative effect in a dose-dependent manner. LRRK2-IN-1 markedly impaired cell proliferation, induced apoptosis, and decreased colony formation capacity and colony size in both iCCA and pCCA compared with the untreated cells. In situ analysis confirmed that DCLK1 is present only in tumors, and not in healthy tissue. Interestingly, DCLK1 was detected in the human serum samples of patients with iCCA (high), pCCA (high), HCC (low), and cirrhosis (low), but it was almost undetectable in healthy controls. CONCLUSIONS: DCLK1 characterizes a specific CSC subpopulation of iCCACD133+ and pCCALGR5+ , and its inhibition exerts anti-neoplastic effects in primary CCA cell cultures. Human DCLK1 serum might represent a serum biomarker for the early CCA diagnosis.


Assuntos
Neoplasias dos Ductos Biliares/genética , Biomarcadores Tumorais/biossíntese , Colangiocarcinoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Receptores Acoplados a Proteínas G/biossíntese , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/patologia , Quinases Semelhantes a Duplacortina , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Células-Tronco Neoplásicas/patologia , Proteínas Serina-Treonina Quinases/genética , Receptores Acoplados a Proteínas G/genética
19.
Int J Biol Markers ; 34(3): 269-275, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31213130

RESUMO

BACKGROUND: Several prognostic factors were proposed to improve early detection of recurrence after liver resection of metastases of colorectal cancer. Circulating tumor cell-related transcripts were evaluated in colorectal cancer patients with conflicting results. The aim of this study was to investigate usefulness of carcinoembryonic antigen CAM5, epidermal growth factor receptor, and ERCC1 transcripts in the bloodstream as predictive factors of recurrence in patients who underwent liver resection for metastases of colorectal cancer. METHODS: Peripheral blood was collected from 29 patients at the time of the colorectal cancer liver metastasis resection, and from 25 normal controls. Follow-up draws (FUDs) were also performed at 30 days, and 3 and 12 months since surgery. On each sample, carcinoembryonic antigen CAM5, ERCC1, and GAPDH mRNAs were examined by quantitative reverse transcription (qRT). RESULTS: Carcinoembryonic antigen transcript levels were linearly correlated to the number of spiked cells (qRT analytical limit = five cells). Among 29 patients (20 M/9 F; mean age 63 years (range 32-79), highly significant levels of carcinoembryonic antigen, if compared to the baseline, were detected in those relapsing after surgery (P <0.05). The main differences were between the 1st- and 12th-month FUDs. Significantly higher levels of carcinoembryonic antigen were also detected in patients who died from disease progression during the follow-up (as evaluated at 30 days and 90 days FUDs). CONCLUSIONS: Blood carcinoembryonic antigen-mRNA absolute copy number overtime variation can represent a valid early predictor of relapse after liver resection in colorectal liver metastases patients. Prospective studies, in the context of large clinical trials, will provide further data to also qualify ERCC1 as a predictive biomarker for decisions on therapeutic strategies.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/sangue , Fígado/cirurgia , Recidiva Local de Neoplasia/sangue , Adulto , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
20.
Eur J Surg Oncol ; 45(11): 2096-2102, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31227342

RESUMO

OBJECTIVE: To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. METHODS: Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors of post-HR progression free survival (PHR-PFS) were assessed by univariate analyses using Cox-proportional hazard regression models. RESULTS: Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr post-HR overall survival was 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to 15.2% in wild type ones (p value: 0.001). CONCLUSIONS: Our clinical analyses suggest that in ROC patients with liver disease the assessment of germline and somatic BRCA mutational status can help to select patients elegible for SCS.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/genética , Neoplasias Hepáticas/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/secundário , Carcinoma Endometrioide/terapia , Carcinoma Epitelial do Ovário/secundário , Carcinoma Epitelial do Ovário/terapia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Mutação em Linhagem Germinativa , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Excisão de Linfonodo , Metastasectomia , Pessoa de Meia-Idade , Mutação , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/secundário , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Compostos de Platina/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/secundário , Neoplasias Esplênicas/terapia
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