Publications by authors named "Gerardo Blanco-Fernández"

33 Publications

Perioperative chemotherapy versus surgery alone for resectable colorectal liver metastases: an international multicentre propensity score matched analysis on long-term outcomes according to established prognostic risk scores.

HPB (Oxford) 2021 May 15. Epub 2021 May 15.

HPB Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain.

Background: There is still uncertainty regarding the role of perioperative chemotherapy (CTx) in patients with resectable colorectal liver metastases (CRLM), especially in those with a low-risk of recurrence.

Methods: Multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010-2015. Patients were divided into two groups according to whether they received perioperative CTx or not and were compared using propensity score matching (PSM) analysis. Then, they were stratified according to prognostic risk scores, including: Clinical Risk Score (CRS), Tumour Burden Score (TBS) and Genetic And Morphological Evaluation (GAME) score.

Results: The study included 967 patients with a median follow-up of 68 months. After PSM analysis, patients with perioperative CTx presented prolonged overall survival (OS) in comparison with the surgery alone group (82.8 vs 52.5 months, p = 0.017). On multivariable analysis perioperative CTx was an independent predictor of increased OS (HR 0.705, 95%CI 0.705-0.516, p = 0.029). The benefits of perioperative CTx on survival were confirmed in patients with CRS and TBS scores ≤2 (p = 0.022 and p = 0.020, respectively) and in patients with a GAME score ≤1 (p = 0.006).

Conclusion: Perioperative CTx demonstrated an increase in OS in patients with CRLM. Patients with a low-risk of recurrence seem to benefit from systemic treatment.
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http://dx.doi.org/10.1016/j.hpb.2021.04.026DOI Listing
May 2021

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Institute of Molecular Pathology Biomarkers, University of Extremadura, 10003 Caceres, Spain.

In certain diseases of the pancreas, pancreatic stellate cells form an important part of fibrosis and are critical for the development of cancer cells. A hypoxic condition develops within the tumor, to which pancreatic stellate cells adapt and are able to proliferate. The consequence is the growth of the tumor. Melatonin, the product of the pineal gland, is gaining attention as an agent with therapeutic potential against pancreatic cancers. Its actions on tumor cells lead, in general, to a reduction in cell viability and proliferation. However, its effects on pancreatic stellate cells subjected to hypoxia are less known. In this study, we evaluated the actions of pharmacological concentrations of melatonin (1 mM-1 µM) on pancreatic stellate cells subjected to hypoxia. The results show that melatonin induced a decrease in cell viability at the highest concentrations tested. Similarly, the incorporation of BrdU into DNA was diminished by melatonin. The expression of cyclins A and D also was decreased in the presence of melatonin. Upon treatment of cells with melatonin, increases in the expression of major markers of ER stress, namely BIP, phospho-eIF2α and ATF-4, were detected. Modulation of apoptosis was noticed as an increase in caspase-3 activation. In addition, changes in the phosphorylated state of p44/42, p38 and JNK MAPKs were detected in cells treated with melatonin. A slight decrease in the content of α-smooth muscle actin was detected in cells treated with melatonin. Finally, treatment of cells with melatonin decreased the expression of matrix metalloproteinases 2, 3, 9 and 13. Our observations suggest that melatonin, at pharmacological concentrations, diminishes the proliferation of pancreatic stellate cells subjected to hypoxia through modulation of cell cycle, apoptosis and the activation of crucial MAPKs. Cellular responses might involve certain ER stress regulator proteins. In view of the results, melatonin could be taken into consideration as a potential therapeutic agent for pancreatic fibrosis.
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http://dx.doi.org/10.3390/ijms22115555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197391PMC
May 2021

Melatonin Modulates the Antioxidant Defenses and the Expression of Proinflammatory Mediators in Pancreatic Stellate Cells Subjected to Hypoxia.

Antioxidants (Basel) 2021 Apr 8;10(4). Epub 2021 Apr 8.

Institute of Molecular Pathology Biomarkers, University of Extremadura, 10003 Caceres, Spain.

Pancreatic stellate cells (PSC) play a major role in the formation of fibrotic tissue in pancreatic tumors. On its side, melatonin is a putative therapeutic agent for pancreatic cancer and inflammation. In this work, the actions of melatonin on PSC subjected to hypoxia were evaluated. Reactive oxygen species (ROS) generation reduced (GSH) and oxidized (GSSG) levels of glutathione, and protein and lipid oxidation were analyzed. The phosphorylation of nuclear factor erythroid 2-related factor (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and the regulatory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα) was studied. The expression of Nrf2-regulated antioxidant enzymes, superoxide dismutase (SOD) enzymes, cyclooxygenase 2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also studied. Total antioxidant capacity (TAC) was assayed. Finally, cell viability was studied. Under hypoxia and in the presence of melatonin generation of ROS was observed. No increases in the oxidation of proteins or lipids were detected. The phosphorylation of Nrf2 and the expression of the antioxidant enzymes catalytic subunit of glutamate-cysteine ligase, catalase, NAD(P)H-quinone oxidoreductase 1, heme oxygenase-1, SOD1, and of SOD2 were augmented. The TAC was increased. Protein kinase C was involved in the effects of melatonin. Melatonin decreased the GSH/GSSG ratio at the highest concentration tested. Cell viability dropped in the presence of melatonin. Finally, melatonin diminished the phosphorylation of NF-kB and the expression of COX-2, IL-6, and TNF-α. Our results indicate that melatonin, at pharmacological concentrations, modulates the red-ox state, viability, and the expression of proinflammatory mediators in PSC subjected to hypoxia.
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http://dx.doi.org/10.3390/antiox10040577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070371PMC
April 2021

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients.

Am J Transplant 2021 Apr 9. Epub 2021 Apr 9.

Department of Hepatology/HPB-surgery/Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain.

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.
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http://dx.doi.org/10.1111/ajt.16599DOI Listing
April 2021

Prospective Study Correlating External Biliary Stenting and Pancreatic Fistula Following Pancreaticoduodenectomy.

J Gastrointest Surg 2021 Mar 25. Epub 2021 Mar 25.

Department of HBP and Liver Transplant Surgery, University Hospital Complex of Badajoz, University of Extremadura, Avda de Elvas, s/n, 06080, Badajoz, Spain.

Background: Postoperative pancreatic fistula (POPF) is the most common complication of pancreaticoduodenectomy (PD). Sometimes POPF is associated with biliary fistula (BF) or "mixed" fistula. The purpose of this study is to assess whether the severity of the fistulae, when present, is decreased with an external biliary stent in place.

Methods: In this single-center study, we assessed patients who underwent elective PD from January 2014 to December 2017. Patients were divided into two groups: standard PD (ST-PD) vs. PD with external biliary stent (PD-BS). Demographic, preoperative, intraoperative, and postoperative variables were analyzed, including complications according to the Clavien-Dindo classification, and those specific to pancreatic surgeries, and mortality rates within 90 days of operation.

Results: A total of 128 patients were included (65 in ST-PD group and 63 in PD-BS group). Postoperative complications occurred in 61.7% of patients (32.8%, Clavien-Dindo ≥ III) and were more common among patients in the PD-BS group (44.4% vs. 23.1%; p = 0.03). POPF was also more common among patients in the PD-BS group (39.7% vs. 18.5%; p = 0.008). No statistically significant differences were found for any other complications.

Conclusion: Based on the results of our study, placement of a transanastomotic external biliary stent does not reduce the rate of pancreatic or biliary fistulae, or their severity; in fact, POPF is more likely when biliary exteriorization is present.

Trial Registration: NCT04654299.
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http://dx.doi.org/10.1007/s11605-021-04983-6DOI Listing
March 2021

Jaundice as a clinical presentation in liver hydatidosis increases the risk of postoperative biliary fistula.

Langenbecks Arch Surg 2021 Jun 2;406(4):1139-1147. Epub 2021 Jan 2.

Department of HBP, General and Digestive Surgery, University Hospital of Alicante, Alicante, Spain.

Purpose: Echinococcosis, also known as hydatidosis, is a zoonosis that is endemic in many countries worldwide. Liver hydatid cysts have a wide variety of clinical manifestations, among which obstructive jaundice is one of the rarer forms. The aims of the study were to analyze the preoperative management of these patients and to record the kind of surgical treatment performed and the short- and long-term postoperative results.

Methods: A retrospective two-center observational study of patients operated upon for liver hydatidosis with initial symptoms of obstructive jaundice. Preoperative characteristics, surgical data, and postoperative complications, including biliary fistula, were recorded.

Results: Of 353 patients operated upon for liver hydatidosis, 44 were included in the study. Thirty-five patients (79.6%) were defined as CE2 or CE3 in the World Health Organization (WHO) classification. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) was performed in 25 patients (56.8%) and identified intrabiliary communication in 29. Radical surgery was carried out in 29 of the total sample (65.9%). Severe postoperative complications (Clavien-Dindo grade IIIA or higher) were recorded in 25% of patients. The factors associated with greater postoperative morbidity were age above 65 (HR 8.76 [95% CI 0.78-97.85]), cyst location (HR 4.77 [95% CI 0.93-24.42]), multiple cysts (HR 14.58 [95% CI 1.42-149.96]), and cyst size greater than 5 cm (HR 6.88 [95% CI 0.95-50]).

Conclusion: The presentation as obstructive jaundice causes greater postoperative morbidity. The main postoperative complication in these cases, despite radical surgery, is biliary fistula. In our series, routine preoperative ERCP did not show any benefit.
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http://dx.doi.org/10.1007/s00423-020-02070-zDOI Listing
June 2021

Implementation of a regional reference center in pancreatic surgery. Experience after 631 procedures.

Cir Esp (Engl Ed) 2020 Dec 17. Epub 2020 Dec 17.

Hospital Universitario de Badajoz, Badajoz, España.

Introduction: The main objective of this study is to determine if our unit meets the quality standards required by the scientific community from the reference centers for pancreatic surgery in terms of peri-operative results. The secondary objectives are to compare the different pancreatic surgery techniques performed in terms of early post-operative morbidity and mortality and to analyze the impact of the resections added in these terms.

Method: Descriptive, retrospective and single-center study, corresponding to the period 2006-2019. The results obtained were compared with the proposed quality standards, by Bassi et al. and Sabater et al., required from the reference centers in pancreatic surgery. The sample was divided according to surgical technique and compared in terms of early post-operative morbidity and mortality, studying the impact of extended vascular and visceral resections. All patients undergoing pancreatic surgery in our unit due to pancreatic, malignant and benign pathology were included, since it was implemented as a reference center. Emergency procedures were excluded.

Results: 631 patients were analyzed. The values ??obtained in the quality standards are in range. The most frequent surgery was cephalic duodenopancreatectomy, which associated higher peri-operative morbidity and mortality rates (p ≤ 0.05). The extended vascular resections impacted the cephalic duodenopancreatectomy group, associating a longer mean stay (p = 0.01) and a higher rate of re-interventions (p = 0.02).

Conclusions: The experience accumulated allows to meet the required quality standards, as well as perform extended resections to pancreatectomy with good results in terms of post-operative morbi-mortality.
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http://dx.doi.org/10.1016/j.ciresp.2020.09.013DOI Listing
December 2020

Preoperative hepatic artery embolization before distal pancreatectomy plus celiac axis resection does not improve surgical results: A Spanish multicentre study.

Surgeon 2020 Oct 3. Epub 2020 Oct 3.

Instituto de Investigación Sanitaria Aragón, Department of Surgery, Hospital Universitari Miguel Servet, Zaragoza, Spain.

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a surgical procedure with high morbidity and mortality performed in patients with locally advanced pancreatic cancer. Preoperative embolization of hepatic artery (PHAE) has been postulated as a technical option to increase resection rate.

Objective: comparison of morbidity and mortality at 90 days, operative time, hospital stay and survival between patients that performed DP-CAR with and without PHAE.

Methods: Observational retrospective multicentre study.

Inclusion Criteria: patient operated in Spanish centers with DP-CAR for pancreatic cancer from April 2004 until 23 June 2018. Preoperative (PHAE, neodjuvant treatment), intraoperative (operative time and blood loss) and postoperative data (morbidity, hospital stay, R0 and survival) were studied. Complications were measured with Clavien classification at 90 days. Specific pancreatic complications were measured using ISGPS classifications. Data were analyzed using R version 3.1.3 (http://www.r-project.org). Level of significance was set at 0.05.

Results: 41 patients were studied. 26 patients were not embolized (NO-PHAE group) and 15 patients received PHAE. Preoperative BMI and percentage of neoadjuvant chemotherapy were the only preoperative variables different between both groups. The operative time in the PHAE group was shorter (343 min) than in the non-PHAE group (411 min) (p < 0.06). Major morbidity (Clavien > IIIa) and mortality at 90 days were higher in the PHAE group than in the non-PHAE group (60% vs 23% and 26.6% vs 11.6% respectively) (p < 0.004). No statistical difference in overall survival was observed between both groups (p = 0.14).

Conclusion: In our study PHAE is not related with less postoperative morbidity. Even more, major morbidity (Clavien III-IV) and mortality was higher in PHAE group.
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http://dx.doi.org/10.1016/j.surge.2020.08.012DOI Listing
October 2020

Distal pancreatectomy with multivisceral resection: A retrospective multicenter study - Case series.

Int J Surg 2020 Oct 26;82:123-129. Epub 2020 Aug 26.

Instituto de Investigación Sanitaria Aragón, Department of Surgery, Hospital Universitario Miguel Servet, Zaragoza, Spain.

Background: Multivisceral resection (MVR) is sometimes necessary to achieve disease-free margins in cancer surgery. In certain patients with pancreatic tumors that invade neighboring organs these must be removed to perform an appropriate oncological surgery. In addition, there is an increasing need to perform resections of other organs like liver not directly invaded by the tumor but which require synchronous removal. The results of MVR in pancreatic surgery are controversial.

Material And Methods: A distal pancreatectomy retrospective multicenter observational study using prospectively compiled data carried out at seven HPB Units. The period study was January 2008 to December 2018. We excluded DP with celiac trunk resection.

Results: 435 DP were performed. In 62 (14.25%) an extra organ was resected (82 organs). Comparison of the preoperative data of MVR and non-MVR patients showed that patients with MVR had lower BMI, higher ASA and larger tumor size. In the MVR group, the approach was mostly laparotomic and spleen preservation was performed only in 8% of the cases, Blood loss and the percentage of intraoperative transfusion were higher in MVR group. Major morbidity rates (Clavien > IIIa) and mortality (0.8vs.4.8%) were higher in the MVR group. Pancreatic fistula rates were practically the same in both groups. Mean hospital stay was twice as long in the MVR group and the readmission rate was higher in the MVR group. Histology study confirmed a much higher rate of malignant tumors in MVR group.

Conclusions: In order to obtain free margins or treat pathologies in several organs we think that DP + MVR is a feasible technique in selected patients; the results obtained are not as good as those of DP without MVR but are acceptable nonetheless. CLINICALTRIALS.

Gov Identifier: NCT04317352.
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http://dx.doi.org/10.1016/j.ijsu.2020.08.024DOI Listing
October 2020

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.

J Hepatol 2021 01 1;74(1):148-155. Epub 2020 Aug 1.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Digestive Diseases, IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain.

Background & Aims: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate.

Methods: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression.

Results: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit.

Conclusions: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged.

Lay Summary: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.
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http://dx.doi.org/10.1016/j.jhep.2020.07.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395653PMC
January 2021

Side-to-side duodenojejunostomy after resection of third and fourth duodenal portions with pancreatic preservation.

Updates Surg 2020 Dec 5;72(4):1105-1113. Epub 2020 Jun 5.

Department of HBP and Liver Transplant Surgery, University Hospital Complex Badajoz, University of Extremadura, Avda de Elvas s/n, 06080, Badajoz, Spain.

Infra-ampullary duodenal lesions are rare and surgical management is controversial. Reconstruction after resection is usually performed by end-to-end or end-to-side duodenojejunostomy. The goal was to analyze our experience, perioperative management, and results after side-to-side duodenojejunostomy. Therefore, we retrospectively evaluated short- and long-term results of surgical resections of third and fourth duodenal portions for several kinds of lesions and reconstruction through duodenojejunostomy performed in our facilities between January 2012 and December 2018. In total, 12 patients were selected for our study, six were male. The median age was 66.3 (IQR: 77.3-59.4). Lesion classification was as follows: 6 cases (50%) of duodenal adenocarcinoma, 4 cases (33.3%) of gastrointestinal stromal tumors (GISTs), and 2 cases (16.7%) of benign pathology. The most frequent clinical presentation was obstruction with vomiting. The surgical technique of choice was resection of third and fourth duodenal portions with a segment of proximal jejunum. Digestive continuity was restored through side-to-side duodenojejunostomy in 11 cases (91.6%). The median operation time was 182.5 min (IQR 237.5-136.3 min). Nine of the 12 patients (75%) did not receive intra- or postoperative blood transfusions. Six patients (50%) experienced complications during post-op. Four of them (33%) experienced major complications (Clavien-Dindo > IIIa) and three required re-op. The median follow-up was 58.3 (95% CI 15-101.5) months. Of the 11 patients with long-term follow-up, 10 have remained asymptomatic during follow-up. The average disease-free survival (DFS) was 43.1 months for adenocarcinoma, and 93 months for GIST. Based on the results of our series, although small, pancreas-sparing duodenectomy could be considered a feasible and safe technique with adequate oncological results. Side-to-side duodenojejunostomy appears to be a safe technique, is easy to perform, and has good functional outcomes. More studies with a larger number of patients are necessary to confirm these findings.
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http://dx.doi.org/10.1007/s13304-020-00823-5DOI Listing
December 2020

Letter in Reply to Pattern of Relapse in Hepatic Hydatidosis and Variables Associated with Its Morbidity and Relapse: Analysis of 238 Cases in a Single Hospital.

J Gastrointest Surg 2020 09 4;24(9):2178-2179. Epub 2020 Jun 4.

Department of HBP and Liver Transplant Surgery, University Complex Hospital Badajoz, University of Extremadura , Avda de Elvas s/n, Badajoz, 06080, Spain.

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http://dx.doi.org/10.1007/s11605-020-04677-5DOI Listing
September 2020

Melatonin modulates red-ox state and decreases viability of rat pancreatic stellate cells.

Sci Rep 2020 04 14;10(1):6352. Epub 2020 Apr 14.

Institute of Molecular Pathology Biomarkers, University of Extremadura, Caceres, Spain.

In this work we have studied the effects of pharmacological concentrations of melatonin (1 µM-1 mM) on pancreatic stellate cells (PSC). Cell viability was analyzed by AlamarBlue test. Production of reactive oxygen species (ROS) was monitored following CM-HDCFDA and MitoSOX Red-derived fluorescence. Total protein carbonyls and lipid peroxidation were analyzed by HPLC and spectrophotometric methods respectively. Mitochondrial membrane potential (ψ) was monitored by TMRM-derived fluorescence. Reduced (GSH) and oxidized (GSSG) levels of glutathione were determined by fluorescence techniques. Quantitative reverse transcription-polymerase chain reaction was employed to detect the expression of Nrf2-regulated antioxidant enzymes. Determination of SOD activity and total antioxidant capacity (TAC) were carried out by colorimetric methods, whereas expression of SOD was analyzed by Western blotting and RT-qPCR. The results show that melatonin decreased PSC viability in a concentration-dependent manner. Melatonin evoked a concentration-dependent increase in ROS production in the mitochondria and in the cytosol. Oxidation of proteins was detected in the presence of melatonin, whereas lipids oxidation was not observed. Depolarization of ψ was noted with 1 mM melatonin. A decrease in the GSH/GSSG ratio was observed, that depended on the concentration of melatonin used. A concentration-dependent increase in the expression of the antioxidant enzymes catalytic subunit of glutamate-cysteine ligase, catalase, NAD(P)H-quinone oxidoreductase 1 and heme oxygenase-1 was detected in cells incubated with melatonin. Finally, decreases in the expression and in the activity of superoxide dismutase were observed. We conclude that pharmacological concentrations melatonin modify the redox state of PSC, which might decrease cellular viability.
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http://dx.doi.org/10.1038/s41598-020-63433-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156707PMC
April 2020

Results of a survey on peri-operative nutritional support in pancreatic and biliary surgery in Spain.

Nutr Hosp 2020 Apr;37(2):238-242

Hospital Universitario Ramón y Cajal.

Introduction: Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (< 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country.
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http://dx.doi.org/10.20960/nh.02895DOI Listing
April 2020

Pancreatic resection for metastatic renal cell carcinoma. A systematic review.

HPB (Oxford) 2020 04 28;22(4):479-486. Epub 2019 Oct 28.

Department of HBP and Liver Transplant Surgery, University Complex Hospital Badajoz, University of Extremadura, Badajoz, Spain.

Background: Renal cell carcinoma (RCC) can lead to secondary pancreatic tumors even years after nephrectomy was performed. Surgical resection in selected patients shows appropriate survival rates.

Methods: A systematic review was performed following PRISMA guidelines. This review finished in May 2019 and included patients with resected pancreatic metastasis(es). The main purpose was to evaluate the results of surgical resection of pancreatic tumors secondary to kidney cancer.

Results: After the screening process of articles, 21 were selected for the systematic review, which included 354 patients, whose disease-free interval (DFI) was 105.11 (0-361.56) months. Of these patients, 34.6% had additional metastases elsewhere at the time of the surgery, and 48.6% were symptomatic. Postoperative morbidity was 40.2%, The 5-year overall survival (OS) rate was 53.9% (26-75).

Conclusion: Pancreatic surgery for the resection of RCC metastasis(es) is considered safe and shows low morbidity and mortality rates among selected patients in medical institutions where this type of procedure is commonly performed.
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http://dx.doi.org/10.1016/j.hpb.2019.10.017DOI Listing
April 2020

Update in pelvic and retroperitoneal sarcoma management: The role of compartment surgery.

Cir Esp (Engl Ed) 2019 Nov 12;97(9):480-488. Epub 2019 Sep 12.

Grupo Tumores Mesenquimales/Sarcomas, AEC, Madrid, España. Electronic address:

Surgery for retroperitoneal sarcomas should be "en bloc" compartmental, which involves resection of unaffected organs. Its upfront use is key, providing a high percentage of resections with negative margins, resulting in a better local control and increased survival in many patients. Preservation of organs should be done in an individualized manner, especially in the pelvic location, and adapted to the histological aggressiveness of the tumor. Preoperative biopsy is able to establish the diagnosis of sarcoma subtype and consequently an adequate perioperative strategy. These patients should be managed by expert surgeons at referral centers with multidisciplinary units and oncology committees. The use of chemotherapy and radiotherapy is not yet well defined, so it is only recommended at referral centers with clinical trials. Currently, this is the only option to offer the best morbidity and mortality rates, as well as possible improvements in the survival of these patients.
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http://dx.doi.org/10.1016/j.ciresp.2019.06.011DOI Listing
November 2019

Postoperative bleeding and biliary leak after liver resection: A cohort study between two different fibrin sealant patches.

Sci Rep 2019 08 19;9(1):12001. Epub 2019 Aug 19.

Department of HBP and liver transplant surgery, Hospital Universitario Infanta Cristina, University of Extremadura, Badajoz, Spain.

Different topical products have been tested in liver resection to get a control of bleeding. This study compares the effectiveness and complications between two haemostatic agents Tachosil versus Hemopatch. A cohort study including patients who underwent liver resection since November 2014 to April 2016 was conducted. The study was performed in a single institution. Demographic variables, intraoperative characteristics and postoperative complications were analysed. A total of 92 patients (50 in Tachosil group and 42 in Hemopatch group) were included. No differences were found in patients who required intraoperative (Tachosil 6 (12%) vs Hemopatch 2 (4.8%); p = 0.28) and postoperative (Tachosil 4 (8%) vs Hemopatch 3 (7.1%); p = 0.87) blood transfusion. There were no differences in length of hospital stay (Tachosil 7.02 ± 4.1 days vs Hemopatch 7.63 ± 9.1; p = 0.67). Overall postoperative complications were similar between both patches (Tachosil 21 (42%) vs Hemopatch 14 (33%); p = 0.48). No differences were found in specific complications, however Hemopatch showed a higher incidence of intraabdominal abscess 5 (11.9%) and vs 0 (0%) p = 0.01.In this study no differences have been found between Hemopatch and Tachosil in the effectiveness and overall postoperative complication after liver resection, although Hemopatch shows a higher incidence of intraabdominal abscess. Further studies are necessary to confirm these findings.
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http://dx.doi.org/10.1038/s41598-019-48529-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700165PMC
August 2019

A survey of Heads of Surgery and Residents on accessibility and employment in liver transplant teams in Spain.

Cir Esp (Engl Ed) 2019 Dec 9;97(10):560-567. Epub 2019 May 9.

Sección de Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Cruces, Bilbao, España; Sección de Trasplantes de la Asociación Española de Cirujanos.

Introduction: The access of surgeons to liver transplant teams in Spain is heterogeneous. This study aims to portray the current human resources of Spanish transplant teams, distribution of transplant duties among team members, how transplant team members acquire their skills, their leaders' view of their future, as well the motivations of Spanish General Surgery residents to choose transplantation as their future career choice.

Methods: Two different surveys were created, one for head surgeons and one for residents, about the number of team members and their training, recruitment, organization of tasks and motivation to work in transplantation. The questionnaires were e-mailed to both the transplant program directors and the surgical residents.

Results: There are on average 8 surgeons in each transplant unit. More than four surgeons perform the hepatectomy in 54.2% of the groups, while the graft implantation is performed by more than 4 surgeons at just 25% of the centers. Forty-two percent of the transplant chiefs advocated a fellowship training system, and 87.5% believe that generational turnover is guaranteed. Out of 525 residents, 101 responded. Regarding training, 12.8% had no interest in transplantation. Concerning their work preferences, 37.6% were not interested in transplantation because it is excessively demanding, and 52.5% would not like to be part of a liver transplant team in the future.

Conclusions: The generational turnover seems to be guaranteed according to liver transplant program directors. The new generations of surgeons generally opt for other areas of surgery other than transplantation. Studies with a greater number of responses are necessary to validate these results.
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http://dx.doi.org/10.1016/j.ciresp.2019.03.018DOI Listing
December 2019

Pattern of Relapse in Hepatic Hydatidosis: Analysis of 238 Cases in a Single Hospital.

J Gastrointest Surg 2020 02 26;24(2):361-367. Epub 2019 Feb 26.

Department of HBP and Liver Transplant Surgery, Hospital Universitario Infanta Cristina, University of Extremadura, Avda de Elvas s/n, 06080, Badajoz, Spain.

Introduction: Hydatidosis is a chronic disease that is endemic and prevalent in certain regions of the world. Surgical treatment is the best option, although its main problem is that there is a high rate of recurrence. The objective of the present study was to assess its therapeutic management and the factors related to its postoperative morbidity and relapse.

Material And Methods: A descriptive and retrospective study was made of 238 patients with hepatic hydatidosis operated from January 2006 to December 2017 at our center. An analysis was made of the variables associated with postoperative morbidity and relapse, and of the temporal pattern of that relapse.

Results: Out of 238 patients, radical surgery was performed in 132 (55.5%) and partial cystectomy in 106 of them (44.3%). The postoperative morbidity was 42% (100/238) and the relapse rate was 7.2% (17/238). The factors associated with greater postoperative morbidity were partial cystectomy (OR, 2.83 (1.47-5.43); p = 0.002), ≥ 2 cysts (OR, 3.22 (1.51-6.86); p = 0.002), and biliary fistula (OR, 4.34 (2.11-8.91); p < 0.0001); and those associated with higher relapse rate were history of hydatidosis (OR, 4.98 (1.76-14.11); p = 0.003) and ≥ 2 cysts (OR, 3.23 (1.14-9.11); p = 0.027). The first relapses appeared after 14 months, with the greatest incidence between 14 and 36 months.

Conclusions: The surgical procedure applied is associated with morbidity but not with that of relapse. The observed relapse pattern demonstrates the need to maintain long-term follow-up, but with no follow-up being necessary in the first year. Broader multicenter and prospective studies are needed to establish more precise recommendations.
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http://dx.doi.org/10.1007/s11605-019-04163-7DOI Listing
February 2020

Hepatic abscess caused by a fishbone: An unusual finding.

Cir Esp (Engl Ed) 2019 Dec 8;97(10):598-600. Epub 2018 Jul 8.

Servicio de Cirugía Hepatobiliopancreática y Trasplante Hepático, Complejo Hospitalario Universitario de Badajoz, Hospital Infanta Cristina, Badajoz, España.

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http://dx.doi.org/10.1016/j.ciresp.2018.05.007DOI Listing
December 2019

Urgent liver transplantation for acute liver failure due Wilson's disease.

Gastroenterol Hepatol 2019 Jun - Jul;42(6):392-393. Epub 2018 Jul 8.

Servicio de Aparato Digestivo, Complejo Hospitalario Universitario Infanta Cristina, Badajoz, España.

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http://dx.doi.org/10.1016/j.gastrohep.2018.05.023DOI Listing
January 2020

Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis.

Sci Rep 2017 09 5;7(1):10420. Epub 2017 Sep 5.

Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.

The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice (AhR-/-) were used to explore whether AhR controls liver regeneration and carcinogenesis by restricting the expansion of stem-like cells and the expression of pluripotency genes. Short-term CCl liver damage was earlier and more efficiently repaired in AhR-/- than in AhR+/+ mice. Stem-like CK14 + and TBX3 + and pluripotency-expressing OCT4 + and NANOG + cells expanded sooner in AhR-/- than in AhR+/+ regenerating livers. Stem-like side population cells (SP) isolated from AhR-/- livers had increased β-catenin (β-Cat) signaling with overexpression of Axin2, Dkk1 and Cyclin D1. Interestingly, β-Cat, Axin2 and Dkk1 also increased during regeneration but more notably in AhR-null livers. Liver carcinogenesis induced by diethylnitrosamine (DEN) produced large carcinomas in all AhR-/- mice but mostly premalignant adenomas in less than half of AhR+/+ mice. AhR-null tumoral tissue, but not their surrounding non-tumoral parenchyma, had nuclear β-Cat and Axin2 overexpression. OCT4 and NANOG were nevertheless similarly expressed in AhR+/+ and AhR-/- lesions. We suggest that AhR may serve to adjust liver repair and to block tumorigenesis by modulating stem-like cells and β-Cat signaling.
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http://dx.doi.org/10.1038/s41598-017-10984-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585208PMC
September 2017

Lemmel's syndrome: Obstructive jaundice secondary to a duodenal diverticulum.

Cir Esp 2017 Nov 22;95(9):550-551. Epub 2017 Mar 22.

Servicio de Cirugía Hepatobiliopancreática y Trasplante Hepático, Hospital Infanta Cristina, Badajoz, España.

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http://dx.doi.org/10.1016/j.ciresp.2017.02.003DOI Listing
November 2017

Leiomyoma of the round ligament of the liver: report of one case.

Rev Esp Enferm Dig 2015 Oct;107(10):644-6

Hospital Infanta Cristina. Badajoz.

Tumoral conditions in the round ligament of the liver are very uncommon and exhibit nonspecific manifestations, hence a high level of suspicion is necessary for their diagnosis. We report the case of a 47-year-old female patient who presented with abdominal pain for several months; imaging studies showed a lesion of indeterminate nature likely connected with the falciform ligament, and only intraoperative findings acknowledged the presence of an apparently benign tumor in the round ligament of the liver, which biopsy confirmed. Following the excision of the round ligament the patient had a favorable course. As this is a pathologically benign lesion we deem its surgical management both advisable and sufficient. However, because of its small prevalence and the scarcity of literature involving this condition, further studies would be needed to provide information on natural history, treatment, and long-term prognosis.
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http://dx.doi.org/10.17235/reed.2015.3725/2014DOI Listing
October 2015

[Inflammatory pseudotumour of the liver. Importance of intra-operative histopathology].

Cir Cir 2015 Mar-Apr;83(2):151-5. Epub 2015 May 16.

Servicio de Cirugía Hepatobiliopancreática y de Trasplante Hepático, Hospital Infanta Cristina, Badajoz, España.

Background: Inflammatory pseudotumour is a rare entity, considered benign, and characterised by inflammatory cell mesenchymal proliferation.

Clinical Case: The case is presented 70 year-old man with fever of unknown origin syndrome. He was diagnosed with liver abscesses (one segment IV, adjacent to gallbladder fundus and segment VI), who progressed slowly after antibiotic treatment. In the absence of a diagnosis, although fine needle puncture-aspiration and different imaging tests were performed, elective surgery was decided. The intra-operative histopathology reported the existence of an inflammatory pseudotumour.

Conclusions: Inflammatory pseudotumours are clinically classified into different types according to their aetiology, varying therapeutic management based on the same. It is very difficult to diagnose because of the absence of symptoms, blood disorders, or specific radiological findings. Definitive diagnosis often requires histopathological confirmation, in most cases by percutaneous liver puncture, but sometimes exploratory laparotomy or even performing a hepatectomy for confirmation is necessary. The natural history of inflammatory pseudotumour is its regression; thus conservative management may be used through regular checks until resolution, or can be treated with antibiotics, anti-inflammatories and even corticosteroids. Surgical resection is indicated for persistent unresolved systemic symptoms despite medical treatment, in those situations where growth is evident, with or without symptoms, when involving the hepatic hilum, and finally, in case where the possibility of malignancy cannot be ruled out.
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http://dx.doi.org/10.1016/j.circir.2015.04.012DOI Listing
April 2016

[Multinodular focal hepatic steatosis].

Cir Esp 2016 Apr 23;94(4):240-1. Epub 2015 Apr 23.

Servicio de Cirugía Hepatobiliar y Trasplante Hepático, Complejo Hospitalario Infanta Cristina, Badajoz, España.

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http://dx.doi.org/10.1016/j.ciresp.2015.02.006DOI Listing
April 2016

Primary Liver PEComa.

Cir Esp 2015 Nov 5;93(9):600-1. Epub 2014 Oct 5.

Servicio de Cirugía Hepatobiliopancreática y Trasplante Hepático, Hospital Infanta Cristina, Badajoz, España.

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http://dx.doi.org/10.1016/j.ciresp.2014.07.011DOI Listing
November 2015

[Non-functioning primary neuroendocrine tumor of the liver with extension to the celiac trunk].

Cir Esp 2015 Jun-Jul;93(6):415-7. Epub 2013 Sep 17.

Servicio de Cirugía Hepatobiliopancreática y Trasplante, Hospital Infanta Cristina, Badajoz, España.

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http://dx.doi.org/10.1016/j.ciresp.2013.06.002DOI Listing
June 2017

[Gastric retention due to a duodenal obstruction secondary to chronic pancreatitis].

Cir Esp 2013 Oct 14;91(8):e49. Epub 2013 May 14.

Servicio de Cirugía Hepatobiliopancreática y Trasplante, Hospital Infanta Cristina, Badajoz, España. Electronic address:

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http://dx.doi.org/10.1016/j.ciresp.2013.01.011DOI Listing
October 2013