Publications by authors named "Luis Sabater"

56 Publications

Multiple small bowel perforations during the treatment of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type.

Br J Haematol 2021 Jun 29;193(5):e39-e42. Epub 2021 Apr 29.

Department of General Surgery, Hospital Clínico, Liver, Biliary and Pancreatic Unit, University of Valencia, Biomedical Research Institute INCLIVA, Valencia, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17229DOI Listing
June 2021

Non-arbitrary minimum threshold of yearly performed pancreatoduodenectomies: National multicentric study.

Surgery 2021 Apr 16. Epub 2021 Apr 16.

Department of Surgery, Liver, Biliary and Pancreatic Unit, Hospital Clínico, University of Valencia, Biomedical Research Institute (INCLIVA), Valencia, Spain.

Background: Annual hospital volume of pancreatoduodenectomies could influence postoperative outcomes. The aim of this study is to establish with a non-arbitrary method the minimum threshold of yearly performed pancreatoduodenectomies in order to improve several postoperative quality outcomes.

Method: Prospective follow-up of patients submitted to pancreatoduodenectomy in participating hospitals during 1 year. The influence of hospital volume on quality outcomes was analyzed by univariable and multivariable models. The minimum threshold of yearly performed pancreatoduodenectomies to improve outcomes was established by Akaike's information criteria.

Results: Data from 877 patients operated in 74 hospitals were analyzed. Of 12 quality outcomes, 9 were influenced by hospital pancreatoduodenectomy volume on multivariable analysis. To decrease the risk of complications and the risk of retrieving an insufficient number of lymph nodes at least 31 pancreatoduodenectomies per year should be performed. To decrease the risk of prolonged length of stay, postoperative death, and affected surgical margins, at least 37, 6, and 14 pancreatoduodenectomies per year should be performed, respectively.

Conclusion: Several postoperative quality outcomes are influenced by the number of yearly performed pancreatoduodenectomies and could be improved by establishing a minimum threshold of procedures. Number of procedures needed to improve quality outcomes has been established by a non-arbitrary method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2021.03.012DOI Listing
April 2021

Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Cancers (Basel) 2021 Feb 27;13(5). Epub 2021 Feb 27.

Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, 46010 Valencia, Spain.

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas's poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13050994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956845PMC
February 2021

What does preoperative three-dimensional image contribute to complex pancreatic surgery?

Cir Esp (Engl Ed) 2021 Jan 27. Epub 2021 Jan 27.

Unidad HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Clínico Universitario de Valencia. Instituto de Investigación Biomédica INCLIVA. Departamento de Cirugía, Universitat de Valencia, Valencia, España.

The possibility of modelling diagnostic images in three dimensions (3D) in pancreatic surgery is a novelty that provides us multiple advantages. A better visualization of the structures allows us a more accurate planning of the surgical technique and makes it easier the surgery in complex cases. We present the case study of a borderline pancreatic head adenocarcinoma patient to illustrate the advantages of 3D modelling in complex pancreatic surgery. The help of 3D technology allowed us to optimally plan the intervention and facilitate surgical resection. The use of this tool could translate into: shorter operative time, fewer intraoperative complications or an increase in R0 resections. The usability of the program used in our case, agile and intuitive, was an added advantage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ciresp.2020.11.021DOI Listing
January 2021

Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.

ESMO Open 2020 11;5(6):e000929

CIBERONC, Instituto de Salud Carlos III, Madrid, Comunidad de Madrid, Spain; Department of Medical Oncology, University of Valencia, Valencia, Spain. Electronic address:

Introduction: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting.

Methods: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient's characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test.

Results: Between August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001).

Conclusion: A neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/esmoopen-2020-000929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684818PMC
November 2020

Surgical treatment of an intraductal papillary mucinous neoplasm of the biliary tract diagnosed by SpyGlass®.

Rev Esp Enferm Dig 2021 Jan;113(1):45-47

Cirugía General y del Aparato Digestivo, Hospital Clínico Universitario de Valencia, España.

We present the case of a 76-year-old male with a history of acute cholecystitis who underwent a scheduled laparoscopic cholecystectomy. Chronic cholecystitis with a thickened cystic duct was observed intraoperatively. The anatomic pathology report found high-grade dysplasia that affected the distal edge of the cystic duct. In view of these findings, an endoscopic retrograde cholangiopancreatography (ERCP) was performed with SpyGlass® and an excrescent lesion suggestive of malignancy adjacent to the cystic-common bile duct junction was observed. A resection of the extrahepatic bile duct was performed with lymphadenectomy of the hepatic hilum and hepaticojejunostomy in a subsequent procedure. The definitive pathology report confirmed pancreaticobiliary intraductal papillary mucinous neoplasia with high-grade dysplasia and free margins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17235/reed.2020.7122/2020DOI Listing
January 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surge.2020.08.012DOI Listing
October 2020

The actual management of colorectal liver metastases.

Minerva Chir 2020 Oct 6;75(5):328-344. Epub 2020 Aug 6.

Unit of Liver, Biliary and Pancreatic Surgery, Department of Surgery, Clinic Hospital, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.

Colorectal cancer is one of the most frequent cancers in the world and between 50% and 60% of patients will develop colorectal liver metastases (CRLM) during the disease. There have been great improvements in the management of CRLM during the last decades. The combination of modern chemotherapeutic and biological systemic treatments with aggressive surgical resection strategies is currently the base for the treatment of patients considered unresectable until few years ago. Furthermore, several new treatments for the local control of CRLM have been developed and are now part of the arsenal of multidisciplinary teams for the treatment of these complex patients. The aim of this review was to summarize and update the management of CRLM, its controversies and relevant evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4733.20.08436-9DOI Listing
October 2020

Impact of type and severity of postoperative complications on long-term outcomes after colorectal liver metastases resection.

J Surg Oncol 2020 Aug 26;122(2):212-225. Epub 2020 Apr 26.

Department of Surgery, Liver, Biliary, and Pancreatic Unit, Biomedical Research Institute INCLIVA, Hospital Clínico University of Valencia, Valencia, Spain.

Background And Objectives: Postoperative complications (POCs) after hepatic resection for colorectal liver metastases (CRLM) adversely affect long-term survival. The aim of this study was to analyze the effect of POC etiology and severity on overall survival (OS) and disease-free survival (DFS).

Methods: A retrospective study of 254 consecutive hepatectomies for CRLM was performed. Univariate and multivariate analyses were performed to determine the effects of demographic, tumor-related and perioperative variables on OS and DFS. A 1:1 propensity score matching (PSM) was then used to compare patients with different POC etiology: infective (Inf-POC), noninfective (Non-inf POC), and no-complications (No-POC).

Results: Inf-POC, Non-inf POC, and No-POC patients represented 18.8%, 19.2%, and 62% of the sample, respectively. In univariate and multivariate analyses infectious POC were independent risk factors for decreased OS and DFS. After PSM, Inf-POC group presented decreased OS and DFS when compared with Non-inf POC (5-year OS 31.8% vs 51.6%; P = .05 and 5-year DFS 13.6% vs 31.9%; P = .04) and with No-POC (5-year OS 29.4% vs 58.7%; P = .03 and 5-year DFS 11.8% vs 39.7%; P = .03). There were no differences between Non-inf POC and No-POC patients. POC severity calculated using the Comprehensive Complications Index did not influence OS and DFS before and after PSM.

Conclusion: The negative oncological impact of POCs after CRLM resection is determined by infective etiology not by severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.25946DOI Listing
August 2020

Response to Comment on "Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy? A Multicenter, Randomized, Controlled Trial".

Ann Surg 2020 Jan 6. Epub 2020 Jan 6.

Department of Surgery, Hospital Clínico, University of Valencia, Biomedical Research Institute INCLIVA, Valencia, Spain Department of Surgery, Hospital Virgen del Rocío, Sevilla, Spain On behalf of all authors.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003773DOI Listing
January 2020

Acute cholecystitis in elderly and high-risk surgical patients: is percutaneous cholecystostomy preferable to emergency cholecystectomy?

J Gastrointest Surg 2020 11 2;24(11):2579-2586. Epub 2019 Dec 2.

Liver, Biliary and Pancreatic Unit, Department of General Surgery, Hospital Clínico, University of Valencia. Biomedical Research Institute INCLIVA, Avd. Blasco Ibañez 17, 46010, Valencia, Spain.

Objective: To investigate whether percutaneous cholecystostomy (PC) for the treatment of acute calculous cholecystitis (ACC) has better results than emergency cholecystectomy (EC) in elderly and high-risk surgical patients.

Methods: Patients ≥ 70 years and/or ≥ ASA-PS 3 with ACC treated with PC or EC between 2005 and 2016 were retrospectively reviewed. Both techniques were compared regarding morbi-mortality, hospital stay, complications and readmissions. A subgroup analysis in higher risk patients (≥ 70 years plus ≥ ASA-PS 3) was also performed. A binary logistic regression analysis for outcome variables to calculate the OR was carried out.

Results: A total of 461 patients were included in the study. The results of PC were worse compared to EC: 30-day mortality (8.6 vs. 1.7%, OR 18.4), 90-day mortality (10.4 vs. 2.1%, OR 10.3), length of stay (days) (13.21 ± 8.2 vs. 7.48 ± 7.67, OR 8.7) and readmission rate (35.1 vs. 12.6%, OR 4.7). Complications were lower for PC (14 vs. 22.6%, OR 0.41), but there were no significant differences in the number of severe complications (Clavien-Dindo ≥ III). Higher-risk subgroup analysis (n = 193; PC = 128, EC = 65) showed similar results to the whole series. Patients with ACC for more than 3 days had more risk of severe complications in both groups (OR 2.26; OR 2.76).

Conclusion: PC was associated with an increased risk of mortality at 30 and 90 days, more readmissions and longer hospital stay. Although PC presents a lower risk of complications, the percentage of severe complications (Clavien-Dindo ≥ III) does not show significant differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-019-04424-5DOI Listing
November 2020

Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy?: A Multicenter, Randomized, Controlled Trial.

Ann Surg 2019 11;270(5):738-746

Department of Surgery, Hospital Virgen del Rocío, Sevilla, Spain.

Objective: To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD).

Background: Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. "Artery-first approach" is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies.

Methods: A multicenter, randomized, controlled trial was conducted in 10 University Hospitals (NCT02803814, ClinicalTrials.gov). Eligible patients were those who presented with pancreatic head adenocarcinoma and periampullary tumors (ampulloma, distal cholangiocarcinoma, duodenal adenocarcinoma). Assignment to each group (ST-PD or AFA-PD) was randomized by blocks and stratified by centers. The primary end-point was the rate of tumor-free resection margins (R0); secondary end-points were postoperative complications and mortality.

Results: One hundred seventy-nine patients were assessed for eligibility and 176 randomized. After exclusions, the final analysis included 75 ST-PD and 78 AFA-PD. R0 resection rates were 77.3% (95% CI: 68.4-87.4) with ST-PD and 67.9% (95% CI: 58.3-79.1) with AFA-PD, P=0.194. There were no significant differences in postoperative complication rates, overall 73.3% versus 67.9%, and perioperative mortality 4% versus 6.4%.

Conclusions: Despite theoretical oncological advantages associated with AFA-PD and evidence coming from low-level studies, this multicenter, randomized, controlled trial has found no difference neither in R0 resection rates nor in postoperative complications in patients undergoing ST-PD versus AFA-PD for pancreatic head adenocarcinoma and other periampullary tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003535DOI Listing
November 2019

The role of endoscopic retrograde cholangiopancreatography in the management of iatrogenic bile duct injury after cholecystectomy.

Rev Esp Enferm Dig 2019 Sep;111(9):690-695

Unidad de Cirugía HBP. Servicio de Cirugía General y del Aparato Digestivo. Departamento de Cirugía. Universitat de Valencia. Valencia, España

Introduction: iatrogenic bile duct injury (IBDI) is a complication with a high morbidity after cholecystectomy. In recent years, endoscopy has acquired a fundamental role in the management of this pathology.

Methods: a retrospective study of IBDI after open cholecystectomy (OC) or laparoscopic cholecystectomy (LC) of patients treated in our center between 1993 and 2017 was performed. Clinical characteristics, type of injury according to the Strasberg-Bismuth classification, diagnosis, repair techniques and follow-up were analyzed.

Results: 46 patients were studied and IBDI incidence was 0.48%, 0.61% for LC and 0.24% for OC. A diagnosis was made intraoperatively in 12 cases (26%) and by endoscopic retrograde cholangiopancreatography (ERCP) in 10 (21.7%) cases. The most common IBDI patient characteristics were acute cholecystitis (20/46, 43.5%), previous admission due to biliary pathology (16/46, 43.2%) and ERCP prior to cholecystectomy (7/46, 18.9%). The most frequent types of IBDI were D (17/46, 36.9%) and A (15/46, 32.6%). The most commonly used treatment was primary suture (13/46, 28.3%) followed by ERCP (11/46, 23.9%) with sphincterotomy and/or stents. In addition, ERCP was performed during the immediate postoperative period in 6 (13%) patients with a surgical IBDI repair in order to resolve immediate complications.

Conclusion: ERCP is useful in the management of IBDI that is not diagnosed intraoperatively. This procedure facilitates the localization of the injured area of the bile duct, therapeutic maneuvers and successful outcomes in postoperative complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17235/reed.2019.6245/2019DOI Listing
September 2019

Impact of Postoperative Complications on Survival and Recurrence After Resection of Colorectal Liver Metastases: Systematic Review and Meta-analysis.

Ann Surg 2019 12;270(6):1018-1027

Department of Surgery, Liver, Biliary and Pancreatic Unit, Hospital Clínico, University of Valencia, Biomedical Research Institute (INCLIVA), Valencia, Spain.

Objective: To study the effect of postoperative complications (POC) on overall survival (OS) and disease-free survival (DFS) after surgical resection of colorectal liver metastases (CRLM).

Summary Background Data: Morbidity rates after liver resection can reach 45%. The negative impact of POC on oncologic outcomes has been reported in various types of cancer, especially colorectal. However, data on the consequences of POC after CRLM resection on long-term survival are scarce.

Methods: Eligible studies examining the association between POC after CRLM resection and OS/DFS were sought using the PubMed and Web of Science databases. A random-effects model was used to calculate pooled effect estimate for OS and DFS hazard ratios (HR), estimating between-study variance with restricted maximum likelihood estimator with Hartung-Knapp adjustment. Subgroup analysis was used to control the effect of POC on OS and DFS for: 1) Method used to define postoperative complications, 2) Exclusion of early postoperative death from survival analysis, 3) Method of data extraction used, and 4) Tumor and treatment characteristics.

Results: Forty-one studies were deemed eligible, including 12,817 patients. POC patients had a significant risk of reduced OS compared with no POC group (HR 1.43 [95% CI: 1.3, 1.57], P < 0.0001). POC had also a negative impact on DFS. The HR for reduced DFS was 1.38 [95% CI 1.27, 1.49], P < 0.0001. The negative impact of POC on survival and recurrence was confirmed in subgroup analysis.

Conclusions: Our findings evidence the negative impact of POC on survival and recurrence after CRLM resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003254DOI Listing
December 2019

Pancreatoduodenectomy with artery-first approach.

Minerva Chir 2019 Jun 2;74(3):226-236. Epub 2019 Jan 2.

Liver, Biliary and Pancreatic Unit, Department of General Surgery, Hospital Clínico, University of Valencia, Spain -

"Artery-first approach" encompasses different aspects for the surgical treatment of pancreatic cancer. It is a surgical technique or set of techniques which share in common the dissection of the main arterial vasculature involved in pancreatic cancer, before any irreversible surgical step is performed. On the other hand it represents the need for a meticulous dissection of the arterial planes and clearing of the retropancreatic tissue between the superior mesenteric artery, the common hepatic artery and portal vein in an attempt to achieve R0 resections. The recent expansion of this approach is based mainly on three factors: venous involvement should not be considered a contraindication for resection, most of the pancreatic resections performed with a standard procedure may be in fact non-oncological (R1) resections and the postero-medial or vascular margin is the most frequently invaded by the tumor. This review aimed to summarize and update the artery-first approach in pancreaticoduodenectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4733.18.07944-0DOI Listing
June 2019

Outcomes after neoadjuvant treatment with gemcitabine and erlotinib followed by gemcitabine-erlotinib and radiotherapy for resectable pancreatic cancer (GEMCAD 10-03 trial).

Cancer Chemother Pharmacol 2018 12 17;82(6):935-943. Epub 2018 Sep 17.

Surgical Department, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.

Background: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.

Methods: Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.

Results: Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009).

Conclusion: The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-018-3682-9DOI Listing
December 2018

Borderline resectable pancreatic cancer. Challenges and controversies.

Cancer Treat Rev 2018 Jul 13;68:124-135. Epub 2018 Jun 13.

CIBERONC Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Spain. Electronic address:

Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by surgery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic cancer, the complexity of its management and controversies and point out where further research and international cooperation for a consensus strategy is urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2018.06.006DOI Listing
July 2018

Outcome quality standards in pancreatic oncologic surgery in Spain.

Cir Esp (Engl Ed) 2018 Jun - Jul;96(6):342-351. Epub 2018 May 19.

Servicio de Cirugía General, Hospital Clínico Universitario de Valencia, Valencia, España; Departamento de Cirugía, Universitat de València, Valencia, España.

Introduction: To establish quality standards in oncologic surgery is a complex but necessary challenge to improve surgical outcomes. Unlike other tumors, there are no well-defined quality standards in pancreatic cancer. The aim of this study is to identify quality indicators in pancreatic oncologic surgery in Spain as well as their acceptable limits of variability.

Methods: Quality indicators were selected based on clinical practice guidelines, consensus conferences, reviews and national publications on oncologic pancreatic surgery between the years 2000 and 2016. Variability margins for each indicator have been determined by statistical process control techniques and graphically represented with the 99.8 and 95% confidence intervals above and below the weighted average according to sample size.

Results: The following indicators have been determined with their weighted average and acceptable quality limits: resectability rate 71% (>58%), morbidity 58% (<73%), mortality 4% (<10%), biliary leak 6% (<14%), pancreatic fistula rate 18% (<29%), hemorrhage 11% (<21%), reoperation rate 11% (<20%) and mean hospital stay (<21 days).

Conclusions: To date, few related series have been published, and they present important methodological limitations. Among the selected indicators, the morbidity and mortality quality limits have come out higher than those obtained in international standards. It is necessary for Spanish pancreatic surgeons to adopt homogeneous criteria regarding indicators and their definitions to allow for the comparison of their results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ciresp.2018.03.002DOI Listing
January 2019

Role of obesity in the release of extracellular nucleosomes in acute pancreatitis: a clinical and experimental study.

Int J Obes (Lond) 2019 01 1;43(1):158-168. Epub 2018 May 1.

Department of Physiology, School of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain.

Background/objectives: A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats.

Methods: DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI). Lipids from pancreatic ascites from lean and obese rats were analyzed and the associated toxicity measured in vitro in RAW 264.7 macrophages. The inflammatory response, extracellular DNA and nucleosomes were determined in lean or obese rats with pancreatitis after peritoneal lavage.

Results: Nucleosome levels in plasma from obese patients with mild pancreatitis were higher than in normal BMI patients; these levels markedly increased in obese patients with moderately severe pancreatitis vs. those with normal BMI. Ascites from obese rats exhibited high levels of palmitic, oleic, stearic, and arachidonic acids. Necrosis and histone 4 citrullination-marker of extracellular traps-increased in macrophages incubated with ascites from obese rats but not with ascites from lean rats. Peritoneal lavage abrogated the increase in DNA and nucleosomes in plasma from lean or obese rats with pancreatitis. It prevented fat necrosis and induction of HIF-related genes in lung.

Conclusions: Extracellular nucleosomes are intensely released in obese patients with acute pancreatitis. Pancreatitis-associated ascitic fluid triggers the release of extracellular nucleosomes in rats with severe pancreatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41366-018-0073-6DOI Listing
January 2019

Is Percutaneous Transhepatic Biliary Drainage Better than Endoscopic Drainage in the Management of Jaundiced Patients Awaiting Pancreaticoduodenectomy? A Systematic Review and Meta-analysis.

J Vasc Interv Radiol 2018 05 13;29(5):676-687. Epub 2018 Mar 13.

Hepatobiliary and Pancreatic Unit, General and Digestive Surgery Department, Hospital Clõnico Universitario de Valencia, Valencia, Spain.

Purpose: To compare postoperative complications in patients who underwent pancreatoduodenectomy after either endoscopic or percutaneous biliary drain (BD).

Material And Methods: Data from studies comparing the rate of postoperative complications in patients who underwent endoscopic BD or percutaneous BD before pancreatoduodenectomy were extracted independently by 2 investigators. The primary outcome compared in the meta-analysis was the risk of postoperative complications. Secondary outcomes were the risks of procedure-related complications, postoperative mortality, postoperative pancreatic fistula, severe complications, and wound infection. For dichotomous variables, the odds ratio (OR) with 95% confidence interval (CI) was calculated.

Results: Thirteen studies, including 2334 patients (501 in the percutaneous BD group and 1833 in the endoscopic group), met the inclusion criteria. Postoperative and procedure-related complication rates were significantly lower in the percutaneous BD group (OR = .7, 95% CI = .52-.94, P = .02 and OR = .44, 95% CI = .23-.84, P = .01, respectively). No significant differences were observed when severe postoperative complications, postoperative mortality, postoperative pancreatic fistula, and wound infection rates were compared.

Conclusions: In patients awaiting pancreatoduodenectomy, preoperative percutaneous BD is associated with fewer procedure-related or postoperative complications than endoscopic drain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2017.12.027DOI Listing
May 2018

mRNA expression profiles obtained from microdissected pancreatic cancer cells can predict patient survival.

Oncotarget 2017 Dec 3;8(62):104796-104805. Epub 2017 Aug 3.

Department of Surgery, University of Valencia, Hospital Clínico Universitario, Instituto de Investigación Sanitaria Clínico de Valencia (INCLIVA), Valencia, Spain.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in developed countries because of its very poor prognosis and high mortality rates. By the time PDAC is usually diagnosed only 20-25% of patients are candidates for surgery, and the rate of survival for this cancer is low even when a patient with PDAC does undergo surgery. Lymph node invasion is an extremely bad prognosis factor for this disease.

Methods: We analyzed the mRNA expression profile in 30 PDAC samples from patients with resectable local disease (stages I and II). Neoplastic cells were isolated by laser-microdissection in order to avoid sample 'contamination' by non-tumor cells. Due to important differences in the prognoses of PDAC patients with and without lymph node involvement (stage IIB and stages I-IIA, respectively), we also analyzed the association between the mRNA expression profiles from these groups of patients and their survival.

Results: We identified expression profiles associated with patient survival in the whole patient cohort and in each group (stage IIB samples or stage I-IIA samples). Our results indicate that survival-associated genes are different in the groups with and without affected lymph nodes. Survival curves indicate that these expression profiles can help physicians to improve the prognostic classification of patients based on these profiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.20076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739601PMC
December 2017

[Recommendations for the diagnosis, staging and treatment of pre-malignant lesions and pancreatic adenocarcinoma].

Med Clin (Barc) 2016 Nov 7;147(10):465.e1-465.e8. Epub 2016 Oct 7.

Servicio de Oncología Médica, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, España.

Background And Objective: Clinical management of adenocarcinoma of the pancreas is complex, and requires a multidisciplinary approach. The same applies for the premalignant lesions that are increasingly being diagnosed. The current document is an update on the diagnosis and management of premalignant lesions and adenocarcinoma of the pancreas.

Patients And Methods: A conference to establish the basis of the literature review and manuscript redaction was organized by the Grupo Español Multidisciplinar en Cáncer Digestivo. Experts in the field from different specialties (Gastroenterology, Surgery, Radiology, Pathology, Medical Oncology and Radiation Oncology) met to prepare the present document.

Results: The current literature was reviewed and discussed, with subsequent deliberation on the evidence.

Conclusions: Final recommendations were established in view of all the above.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.medcli.2016.07.033DOI Listing
November 2016

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

Ann Surg 2016 Dec;264(6):949-958

*Department of Surgery, Hospital Clinico, University of Valencia, Valencia, Spain †Department of Surgery, Complejo Hospitalario Universitario de Vigo, Vigo, Spain ‡Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands §Department of Gastroenterology, Consorci Sanitari de Terrassa, Terrassa, Spain ¶Department of Gastroenterology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain ||Department of Surgery, Università Vita e Salute, Ospedale San Raffaele IRCCS, Milano, Italy **Department of Surgery, Institut de Malalties Digestives I Metabòliques, Hospital Clínic, IDIBAPS, Barcelona, Spain ††Department of Medicine, Pancreas Center, University of Verona, Verona, Italy ‡‡Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. §§Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ¶¶Department of Surgery, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. ||||Department of Surgery, Hospital Universitario de La Princesa, Madrid, Spain ***Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona, Spain †††Unidad de Cirugía Hepato-bilio-pancreática y Trasplante, Hospital Universitari i Politecnic. La Fe, Valencia, Spain ‡‡‡NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK §§§Department of Gastroenterology, Hospital Clinico, University of Valencia, Valencia, Spain ¶¶¶Unit of Digestive Disease, Agencia Sanitaria Costa del Sol, Marbella, Málaga ||||||Department Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy ****Department of Surgery, Hospital Universitario de Guadalajara, Guadalajara, Spain ††††Department of HPB Surgery and Liver Transplantation, Hospital Carlos Haya, Malaga, Spain ‡‡‡‡Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain §§§§Department of Digestive Surgery- Division of HBP Surgery, Hospital Universitario Donostia, San Sebastián, Spain ¶¶¶¶Department of Gastroenterology, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, IDIBAPS, CiberEHD, Barcelona, Spain ||||||||Department of Gastroenterology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain.

Objective: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery.

Background: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients.

Methods: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement.

Results: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement.

Conclusions: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000001732DOI Listing
December 2016

Pancreatic ascites haemoglobin up-regulates the HIF/VEGF pathway in the lung in severe acute pancreatitis.

Free Radic Biol Med 2014 Oct 10;75 Suppl 1:S44. Epub 2014 Dec 10.

School of Pharmacy (University of Valencia), Physiology, Spain.

Extracellular haemoglobin (EHb) is considered a toxic molecule due to its cytotoxicity and peroxidase activity. EHb may release free hemin that increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain cell-free hemoglobin. Our aim was to determine the role of EHb in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end, taurocholate-induced necrotizing pancreatitis in rats was used. EHb levels were quantified in ascites and plasma and the hemolytic action of ascitic fluid was tested. Furthermore, we assessed if peritoneal lavage prevented the increase in EHb levels in plasma during pancreatitis. Finally, hemoglobin was purified from rat erythrocytes and administered i.p. to assess the local and systemic effects of ascitic-associated EHb during acute pancreatitis. EHb levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in cell-free hemoglobin in plasma. The administration of EHb enhanced ascites, dramatically increased abdominal fat necrosis, up-regulated tumor necrosis factor-a, interleukin 1ß and interleukin 6 gene expression and decreased expression of interleukin 10 in abdominal adipose tissue during pancreatitis. EHb enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia inducible factor-related genes [inducible nitric oxide synthase (inos), endothelial nitric oxide synthase (enos) and hexokinase 2] in the lung. EHb also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation and increasing VEGF and leukocyte infiltration in the lung.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2014.10.801DOI Listing
October 2014

[Pseudoaneurysm of the superior mesenteric artery after pancreatoduodenectomy].

Gastroenterol Hepatol 2016 Jun-Jul;39(6):400-2. Epub 2015 Jun 19.

Servicio de Cirugía General y Aparato Digestivo, Departamento de Cirugía, Hospital Clínico Universitario, Valencia, España. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gastrohep.2015.05.003DOI Listing
November 2017

Redox signaling in acute pancreatitis.

Redox Biol 2015 Aug 28;5:1-14. Epub 2015 Jan 28.

Department of Physiology, University of Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Spain. Electronic address:

Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2015.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360040PMC
August 2015

Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

Free Radic Biol Med 2015 Apr 23;81:145-55. Epub 2014 Aug 23.

Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot, Valencia, Spain. Electronic address:

Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation and by increasing VEGF and leukocyte infiltration into the lung.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2014.08.008DOI Listing
April 2015

Prognostic implications of the standardized study of resection margins in pancreatic cancers.

Cir Esp 2014 Oct 28;92(8):532-8. Epub 2014 May 28.

Servicio de Cirugía General, Instituto de Investigación Sanitaria INCLIVA, Departamento de Cirugía, Universitat de València, Valencia, España.

Introduction: Involvement of surgical resection margins is a fundamental prognostic factor in pancreatic oncological surgery. However, there is a lack of standardized histopathology definition. The aims of this study are to investigate the real rate of R1 resections when surgical specimens are evaluated according to a standardized protocol and to study its survival implications.

Patients Y Methods: One hundred consecutive surgically resected patients with pancreatic ductal adenocarcinoma were included in the study. They were further divided in 2 groups: pre-protocol, evaluated before the introduction of the standardized protocol and post-protocol, analyzed with the standardized protocol.

Results: R0 resection rate in the pre-protocol group was 78%, falling to 47% after the introduction of the standardized protocol (p=0,003). The posterior retroperitoneal margin was the most frequently involved margin. In cases with tumors located at the pancreatic head and analyzed according to the standardized protocol R1 involvement negatively affected survival. Median survival in the R0 group was 22 months versus 16 in those with the margin involved (HR: 2.044; IC 95% 1,00-4,16; P=.043).

Conclusions: Standardized evaluation of the retroperitoneal margins in pancreatic cancer increases the rate of R1 patients. In cases with pancreatic cancer located at the pancreatic head involvement of posterior retroperitoneal margin significantly decreases survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ciresp.2013.07.014DOI Listing
October 2014

Disulfide stress: a novel type of oxidative stress in acute pancreatitis.

Free Radic Biol Med 2014 May 20;70:265-77. Epub 2014 Jan 20.

Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot (Valencia), Spain. Electronic address:

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis. Protein cysteinylation was undetectable in pancreas under basal conditions. Targets of disulfide stress were identified by Western blotting, diagonal electrophoresis, and proteomic methods. Cysteinylated albumin was detected. Redox-sensitive PP2A and tyrosine protein phosphatase activities diminished in pancreatitis and this loss was abrogated by N-acetylcysteine. According to our findings, disulfide stress may be considered a specific type of oxidative stress in acute inflammation associated with protein cysteinylation and γ-glutamylcysteinylation and oxidation of the pair cysteine/cystine, but without glutathione oxidation or changes in protein glutathionylation. Two types of targets of disulfide stress were identified: redox buffers, such as ribonuclease inhibitor or albumin, and redox-signaling thiols, which include thioredoxin 1, APE1/Ref1, Keap1, tyrosine and serine/threonine phosphatases, and protein disulfide isomerase. These targets exhibit great relevance in DNA repair, cell proliferation, apoptosis, endoplasmic reticulum stress, and inflammatory response. Disulfide stress would be a specific mechanism of redox signaling independent of glutathione redox status involved in inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2014.01.009DOI Listing
May 2014

Outcome quality standards in pancreatic oncologic surgery.

Ann Surg Oncol 2014 Apr 6;21(4):1138-46. Epub 2014 Jan 6.

Department of Surgery, Hospital Clínico, University of Valencia, Valencia, Spain,

Purpose: To identify quality indicators and establish acceptable quality limits (AQLs) in pancreatic oncologic surgery using a formal statistical methodology.

Methods: Indicators have been identified through systematic literature reviews and guidelines for pancreatic surgery. AQLs were determined for each indicator with confidence intervals of 99.8 and 95 % above and below the weighted average by sample size from the different series examined.

Results: Several indicators have been identified with the following results as AQLs: resectability rate >59 %; morbidity, mortality, and pancreatic fistula rate in pancreaticoduodenectomy <55, <5, and <16 %, respectively; morbidity, mortality, and fistula rate in distal pancreatectomy <53, <4, and <31 %, respectively; number of lymph nodes retrieved >15; R1 resection <46 %; survival at 1, 3, and 5 years >54, >19, and >8 %, respectively.

Conclusions: A series of different indicators for quality surgical care outcome in pancreatic cancer, as well as their limits, have been determined according to a standard methodology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-013-3451-2DOI Listing
April 2014
-->