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1.
J Transl Med ; 20(1): 14, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986854

RESUMO

BACKGROUND: A growing number of clinical trials have shown that regulatory T (Treg) cell transfer may have a favorable effect on the maintenance of self-tolerance and immune homeostasis in different conditions such as graft-versus-host disease (GvHD), solid organ transplantation, type 1 diabetes, and others. In this context, the availability of a robust manufacturing protocol that is able to produce a sufficient number of functional Treg cells represents a fundamental prerequisite for the success of a cell therapy clinical protocol. However, extended workflow guidelines for nonprofit manufacturers are currently lacking. Despite the fact that different successful manufacturing procedures and cell products with excellent safety profiles have been reported from early clinical trials, the selection and expansion protocols for Treg cells vary a lot. The objective of this study was to validate a Good Manufacturing Practice (GMP)-compliant protocol for the production of Treg cells that approaches the whole process with a risk-management methodology, from process design to completion of final product development. High emphasis was given to the description of the quality control (QC) methodologies used for the in-process and release tests (sterility, endotoxin test, mycoplasma, and immunophenotype). RESULTS: The GMP-compliant protocol defined in this work allows at least 4.11 × 109 Treg cells to be obtained with an average purity of 95.75 ± 4.38% and can be used in different clinical settings to exploit Treg cell immunomodulatory function. CONCLUSIONS: These results could be of great use for facilities implementing GMP-compliant cell therapy protocols of these cells for different conditions aimed at restoring the Treg cell number and function, which may slow the progression of certain diseases.

2.
Cancers (Basel) ; 13(24)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34944880

RESUMO

Complete resection of perihilar cholangiocarcinoma (pCCA) is the only potentially curative treatment. Long-term survival data is rare and prognostic analyses are hindered by the rarity of the disease. This study aimed to determine the cure rate and to identify clinicopathological factors that may preclude cure. All consecutive resections for pathologically confirmed pCCA between 2000 and 2009 in 22 centers worldwide were included in a retrospective cohort study. Each center included its retrospective data series. A total of 460 patients were included with a median follow-up of 10 years for patients alive at last follow-up. Median overall survival (OS) was 29.9 months and 10-year OS was 12.8%. Twenty-nine (6%) patients reached 10-year OS. The observed cure rate was 5%. Factors that virtually precluded cure (i.e., below 1%) according to the mixture cure model included age above 70, Bismuth-Corlette type IV tumors, hepatic artery reconstruction, and positive resection margins. Cure was unlikely (i.e., below 3%) in patients with positive lymph nodes or poor tumor differentiation. These factors need to be considered in patient counseling and long-term follow-up after surgery.

3.
J Hepatol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774638

RESUMO

BACKGROUND & AIMS: In Italy, since August 2014, LT candidates with MELD≥30 receive a national allocation priority. This multi-center cohort study aims to evaluate waiting time in the list, dropout rate, and graft survival before and after introducing the macroarea sharing policy. METHODS: 4,238 patients registered from 2010 to 2018 have been enrolled and categorized in an ERA-1 Group (n=2,013; before August 2014) and an ERA-2 Group (n=2,225; during and after August 2014). Cox proportional hazard model was used to estimate the HR of receiving LT or death between the two ERAs. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: MELD≥30 patients had a lower median waiting time in the list for LT (4vs.12 days, p<0.001) and a higher probability to be transplanted (HR=2.27, 95%CI 1.78-2.90; p=0.001) in the ERA-2 when compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio=0.56, 95%CI=0.46-0.68; p=0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high volume center and ERA-2, while MELD≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD≥30 priority allocation was associated with improved patient outcomes, although MELD≥30 had a higher risk of graft loss. The transplant centers volume and competition among centers may have a role in the recipient prioritization and outcome. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: After introducing the Italian national MELD≥30 priority, more LT, fewer dropouts, and shorter waiting times were observed in patients with MELD≥30. However, a higher risk of graft loss still burdens these cases compared to MELD<30. The volume of transplant centers and competitions among centers may have a role in the recipient prioritization and outcome.

4.
HPB (Oxford) ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34642089

RESUMO

BACKGROUND: The Textbook Outcome (TO) is a quality indicator accounting for both efficacy and safety. Herein, we aimed to assess TO in patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). METHODS: All consecutive patients undergoing RFA for HCC between 2014 and 2020, were included. TO was defined as 1) no post-RFA complications or mortality within 30 days after RFA, 2) no prolonged hospital stay 3) no 30-day readmission and 4) the achievement of a complete response (CR) of the target lesion/s at 1-month. RESULTS: Overall, 50.3% of 376 patients fulfilled all the quality indicators to achieve TO. Probabilities of TO achievement decreased in presence of moderate comorbidities (odds ratio[OR]:0.43; 95%C.I.:0.22-0.80;p=0.008), a performance status of 1 (OR: 0.58;95%C.I.:0.37-0.89; p=0.013), the treatment of 2 nodules (OR: 0.71; 95%C.I.:0.41-0.98; p=0.048) or ≥3 nodules (OR: 0.41; 95%C.I.: 0.22 - 0.78; p = 0.007); the treatment of 2-3cm nodules (OR:0.49;95%C.I.:0.31-0.79;p=0.003) or >3cm nodules (OR: 0.36;95%C.I.:0.18-0.73;p=0.004). Risk-stratification provided TO achievement ranging between 77.9% and 14.3%. Patients with TO also had improved survival (p = 0.028). CONCLUSION: About half of patients get TO from RFA. Stratification by clinical and tumoral characteristic should aid provision of RFA in clinical practice, facilitating patient information and providing reference values for future comparative studies.

5.
J Hepatol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34655663

RESUMO

BACKGROUND: To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups. METHODS: Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide. The following benchmark cut-offs for the most relevant outcome parameters were developed: ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively. Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort.

6.
Updates Surg ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34714535

RESUMO

The study's main goal was the diagnostic adequacy of pancreatic endoscopic ultrasonographic (EUS) fine-needle biopsy (FNB) and associated predictive factors. The secondary objective was to define the diagnostic accuracy of EUS-FNB in the diagnosis of pancreatic masses and pancreatic malignancies. None of the studies reported the diagnostic adequacy and accuracy of EUS. We retrospectively identified patients with solid pancreatic lesions that underwent EUS-FNB between 2013, and 2018. We calculated diagnostic adequacy and related factors. Using definitive histology on the surgically resected specimen as the gold standard, we calculated diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNB. We identified a total of 463 procedures. Diagnostic specimens were adequate in 436 procedures (94.1%), while 27 biopsies provided insufficient samples (5.9%). The multivariate analysis showed that lesion size and needle caliper were the only factors influencing diagnostic adequacy. The use of a biopsy needle (OR 0.69, 95% CI 0.30-0.1.63, P 0.400) did not improve sample adequacy. We calculated sensitivity (100%), specificity (93.2%), diagnostic accuracy (93.2%), positive predictive value (97.1%), and negative predictive value (100%) using resected specimen as the gold standard. We found no significant complications. EUS-FNB is a reliable technique for the histological characterization of solid pancreatic masses.

7.
J Artif Organs ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652561

RESUMO

Left ventricular assist device (LVAD) support in donors may contribute in preserving proper haemodynamics and systemic perfusion during organ retrieval thus decreasing the risk of multiple organ injury. This is an option to expand the current organ supply. We report on intra-abdominal organs procurement strategy in a selected LVAD recipient who suffered a fatal cerebrovascular accident at the time of COVID-19 pandemic outbreak. The liver and kidneys grafts have been successfully transplanted.

9.
Colorectal Dis ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523208

RESUMO

AIM: Textbook outcome (TO) is a new surgical quality measure that combines structure, process and surgical outcomes into a single element. Our study aimed to determine the incidence of TO after simultaneous rectal and liver surgery and to use the achievement of TO as a tool to identify the best candidates for these complex procedures. METHODS: In total, 256 patients who underwent simultaneous liver and rectal surgery for Stage IV rectal cancer between January 2004 and August 2019 at five tertiary centres were enrolled. TO was defined as a lack of complication, prolonged length of stay, readmission and death. RESULTS: Mortality rate at 90 days and major morbidity rate were 2.3% and 15.6%, respectively. An overall TO was achieved in 59% of the patients, which is associated with significantly improved overall (median TO 86.3 months vs. no TO 37.4 months) and disease-free (median TO 70.6 months vs. no TO 24.9 months) survival. On multivariate analysis the presence of multi-comorbidities (OR 3.073) was associated with a reduced likelihood of achieving TO. Left lateral sectionectomy/limited resection was a protective factor (OR 0.416). CONCLUSION: TO was achieved in six of 10 patients undergoing simultaneous resections for rectal cancer and liver metastases. Achieving a TO is strongly associated with improved long-term survival. The best candidates for these procedures were patients without multiple comorbidities and those treated with left lateral sectionectomy/limited resection.

12.
Clin Transplant ; 35(11): e14448, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34363412

RESUMO

Grafts from donors with cardiac death (DCD) are subject to warm ischemia time (WIT) due to the no-touch-period (20 min in Italy and 5 min in France). These livers (LT) have higher rates of early allograft dysfunction (EAD), primary non-function (PNF), and ischemic cholangiopathy (IC) compared to LT from brain dead donors (DBD). Normothermic regional perfusion (NRP) is a beneficial strategy to mitigate organ damage; a further approach is the application of ex vivo hypothermic oxygenated perfusion (HOPE) after cold storage (CS). We retrospectively analyzed LTs performed from 2016 to 2019 at three transplant centers using NRP-DCD grafts: Bologna and Milan treated with HOPE (group A), Rennes preserved using CS (group B). No-flow period, total and functional WIT were significantly higher in group A than in group B (30.5±7.7 vs. 20.5±4.1; 56.5±20.4 vs. 39.1±21.6; 41.9±12.5 vs. 25.5±3.7; respectively, P < .05), without differences in the postoperative course. In particular, the two groups had similar rates of EAD (21.1% vs. 25.0%), PNF (5.3% vs. 6.3%), IC (0% vs. 12.5%, P = .112), and non-IC biliary complications (0% vs. 6.3%, P = .457), re-LT (10.5% vs.12.5%). This occurred despite a high rate of UK DCD risk score > 10 (63.2% A vs. 17.6% B, P = .000), which theoretically would make a large number of these transplants "futile." In conclusion, Italian and French groups had similar post-LT outcomes, probably related to the use of HOPE after CS in the case of long WIT.

13.
Liver Transpl ; 27(12): 1758-1766, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34355489

RESUMO

Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our "Superdownstaging" protocol. Patients received yttrium-90 TARE and were enlisted for DDLT in case of complete and sustained (6 months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5-year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P = 0.03). Three out of 5 patients developed recurrence within 1 year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.

14.
World J Surg ; 45(11): 3424-3435, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34313830

RESUMO

BACKGROUND: The aim of the study was to evaluate perioperative outcomes and to evaluate factors influencing rative morbidity and adoption of minimally invasive technique in 1-team (1-T) versus two teams (2-T) management of synchronous colorectal liver metastases. METHODS: Within four referral centers, a group of 234 patients treated in 1-T centers was identified and compared with a group of 253 patients treated in 2-T. A nonparametric bootstrap process was applied to the original cohorts of 1-T group and 2-T group as a resampling method to obtain bootstrapped cohorts (155 patients per group). RESULTS: 33.5% of patients in 1-T boot group and 38.1% in the 2-T boot group were operated by laparoscopic approach. Multivariate analysis revealed that approach to primary tumor (laparoscopic or open) and intraoperative blood loss were independent prognostic factors for morbidity. Team approach did not show any significant correlation with incidence of postoperative complications nor with choice for laparoscopic approach. CONCLUSION: The optimization of team strategy for patients with SCRLM is not solely based on the adoption of a 1-T or 2-T approach, but should instead be based on the implementation of a standard protocol for management of these patients.


Assuntos
Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Perda Sanguínea Cirúrgica , Neoplasias Colorretais/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
15.
Eur Radiol ; 31(12): 8903-8912, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34117911

RESUMO

OBJECTIVES: To evaluate the inter-observer reliability of modified Response Evaluation Criteria In Solid Tumours (mRECIST) of patients with hepatocellular carcinoma (HCC) undergoing neo-adjuvant treatments before liver transplant (LT). The agreement of tumor number, size, transplant criteria, and the radiological-pathological concordance were also assessed. METHODS: A total of 180 radiological studies before/after neo-adjuvant therapies performed on 90 patients prior to LT were reviewed from three expert centers. Kappa-statistic and intraclass correlation (ICC) were evaluated on mRECIST and on tumoral features. Complete radiological response (CR) was compared with complete pathological response (CPR). RESULTS: Before neo-adjuvant therapies, the agreement on tumor number, size, and transplant criteria ranged from moderate (defined as ICC of 0.41-0.60) to almost perfect (ICC of 0.81-0.99), being higher with magnetic resonance imaging (MRI) than CT (0.657-0.899 and 0.422-0.776, respectively). After neo-adjuvant therapies, the agreement decreased, as ICCs ranged between 0.518 and 0.663 with MRI and between 0.508 and 0.677 with CT. Concordant mRECIST pairs were 201 of 270 reviews (76.3%) with a kappa of 0.648 indicating substantial agreement. When the three observers completely agreed on CR, the positive predictive value for CPR was 51.6%. The negative predictive value was 94.2% with a kappa of 0.512 indicating fair agreement between radiology and pathology. CONCLUSIONS: mRECIST agreement was substantial among the three observers involved. The agreement on tumor number, size, and transplant criteria ranged from moderate to almost perfect, with the highest ICCs obtained with MRI before neo-adjuvant therapies. Finally, the predictive value of mRECIST in the diagnosis of CPR was only fair. KEY POINTS: • The review of 180 radiological exams of patients with hepatocellular carcinoma before and after neo-adjuvant therapies showed that the concordance among three different raters on mRECIST diagnosis was substantial. • The inter-observer reliability on fulfilment of transplant criteria slightly decreased when evaluated through CT and after loco-regional therapies. • The radiological diagnosis of complete response after neo-adjuvant therapies was predictive of complete pathological response in only 51.6% of cases.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Reprodutibilidade dos Testes , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos
16.
17.
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
18.
Cancers (Basel) ; 13(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063501

RESUMO

Hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a previous HR is supposed to worsen post-SLT outcomes. Data of patients treated by SLT between 2000 and 2018 at two tertiary referral centers were analyzed. The primary outcome of the study was to analyze the impact of HR on post-LT complications. A Comprehensive Complication Index ≥ 29.6 was chosen as cutoff. The secondary outcome was HCC-related death by means of competing-risk regression analysis. In the study period, 140 patients were included. Patients were transplanted in a median of 23 months after HR (IQR 14-41). Among all the features analyzed regarding the prior HR, only time interval between HR and SLT (time HR-SLT) was an independent predictor of severe complications after LT (OR = 0.98, p < 0.001). According to fractional polynomial regression, the probability of severe complications increased up to 15 months after HR (43%), then slowly decreased over time (OR = 0.88, p < 0.001). There was no significant association between HCC-related death and time HR-SLT at the multivariable competing risks regression model (SHR, 1.06; 95% CI: 0.69-1.62, p = 0.796). This study showed that time HR-SLT was key in predicting complications after LT, without affecting HCC-related death.

20.
Ann Surg Oncol ; 28(12): 7719-7729, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33956275

RESUMO

BACKGROUND: Although Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database. METHODS: Uni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA. RESULTS: Among 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60). CONCLUSIONS: In this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/cirurgia , Bismuto , Colangiocarcinoma/cirurgia , Hepatectomia , Humanos , Tumor de Klatskin/cirurgia , Estudos Retrospectivos
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