Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience / Influencia del origen e histopatología tumoral tras la resección de metástasis hepáticas de origen no colorrectal no neuroendocrino. Experiencia unicéntrica

Introduction: It remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM. Method: A retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed. Results: A total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively. Conclusion: Based on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection. (AU)

Introducción: No está totalmente aclarado si la resección hepática está justificada en pacientes con metástasis hepáticas no colorrectales no neuroendocrinas (MHNCNN). Hemos realizado un estudio en un solo centro para analizar la supervivencia global (SG), la supervivencia libre de enfermedad (SLE) y posibles factores pronósticos en pacientes con diferentes tipos de MHNCNN. Método: Se realizó un análisis retrospectivo de todos los pacientes que se sometieron a resección hepática de MHNCNN desde enero de 2006 hasta julio de 2019. Resultados: Se analizaron un total de 62 pacientes. El 82,3% presentó metástasis metacrónicas y el 74,2% fueron unilobares. El sitio original del tumor primario (STP) más frecuente fue mama (24,2%), tracto urinario (19,4%), melanoma (12,9%) y páncreas (9,7%). Las histopatologías tumorales primarias más frecuentes fueron el carcinoma de mama (24,2%), el adenocarcinoma no mamario (21%), el melanoma (12,9%) y el sarcoma (12,9%). El procedimiento quirúrgico realizado con mayor frecuencia fue la hepatectomía menor (72,6%). La resección R0 se logró en el 79,5% de los casos. La tasa de complicaciones mayores fue del 9,7% con una tasa de mortalidad a los 90 días del 1,6%. La tasa de SG / SLE a 1, 3 y 5 años fue de 65% / 28%, 45% / 36% y 46% / 28%, respectivamente. Identificamos la respuesta a la terapia neoadyuvante y el STP como posibles factores pronósticos de SG (p = 0,06) y SLE (p = 0,06) respectivamente. Conclusión: Según los resultados de nuestra serie, la resección de MHNCNN produce resultados beneficiosos en términos de SG y SLE. El STP y la respuesta a la terapia neoadyuvante podrían ser los principales factores pronósticos tras la resección. (AU)

Textbook outcome in the surgical treatment of liver hydatid cyst.

BACKGROUND: Textbook outcome is a composite measure used in surgery to define the ideal postoperative period and to assess the quality of care. The aim of this study was to analyze the incidence of textbook outcome and the factors independently associated with its achievement following surgical treatment of liver hydatid cysts. METHODS: Retrospective cohort study of patients operated on for liver hydatid cysts between January 2006 and December 2021. Textbook outcome was achieved when all the following criteria were fulfilled: no mortality within 90 days, no major complications within 90 days, no hospital readmission within 90 days, and no prolonged hospital stay. Univariable and multivariable analyses were performed to identify factors associated with textbook outcome. RESULTS: During the study period, 296 patients underwent surgery. Textbook outcome was recorded in 65.9% (195/296). Female gender (odds ratio 2.02; P = .010), noncomplicated cyst (odds ratio 3.97, P < .001), and radical surgery (odds ratio 2.26, P = .003) were the variables associated with a higher probability of achieving textbook outcome. CONCLUSION: Textbook outcome may be a useful measure to assess the variations in surgical management between different centers, and to improve quality of care after liver hydatid cysts resection.

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience.

INTRODUCTION: It remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM. METHOD: A retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed. RESULTS: A total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications' rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively. CONCLUSION: Based on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.

Resection of isolated pancreatic metastases from pulmonary neoplasia: a systematic review.

Several types of cancers have been reported to metastasize to the pancreas. Lung cancer with isolated pancreatic metastasis is extremely rare. In selected patients, surgery is advocated. The aim of our study is to carry out a systematic review of the articles published on the surgical treatment of these patients. Our goal was to realize a systematic review in accordance with PRISMA guidelines. We conducted a literature search using MEDLINE (PubMed), EMBASE and SCOPUS databases to identify all studies published from 1967 to 2020 reporting patients with pancreatic resection for metastatic lung cancer to the pancreas. The data of the articles finally selected were represented in tables. The median age of included patients was calculated as well as the median survival. The proportion of patients was calculated according to sex, type of surgery performed and location of the lesion. 3150 articles were included at the beginning. After the screening process, 20 articles were selected for the systematic review. These articles reported data on 23 patients. Presentation was mainly metachronous, with a disease-free interval of 10 (0-54) months. Of these patients, 43.5% were symptomatic at diagnosis and 34.8% had extrapancreatic metastases. Mean overall survival was 17.65 (± 14.56) months. Based in this review, there is limited evidence on the treatment due to the small number of published articles, most of them being case report. Surgical resection of pancreatic metastases from lung cancer could be a safe procedure and it could improve survival rates in selected patients.

Adenosquamous cancer of the pancreas: A multicenter retrospective study / Cancer adenoescamoso de pancreas. Estudio retrospectivo multicéntrico

Introduction: Adenosquamous cancer of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Methods: Multicenter retrospective observational study carried out at three Spanish hospitals. The study period was: January 2010–August 2020. A descriptive analysis of the data was performed, as well as an analysis of global and disease-free survival using the Kaplan–Meier statistic. Results: Of a total of 668 pancreatic cancers treated surgically, twelve were ASCP (1.8%). Patient mean age was 69.2±7.4 years. Male/female ratio was 1:1. The main symptom was jaundice (seven patients). Correct preoperative diagnosis was obtained in only two patients. Nine pancreatoduodenectomies and three distal pancreatosplenectomies were performed. 25% had major complications. Mean tumor size was 48.6±19.4mm. Nine patients received adjuvant chemotherapy. Median survival time was 5.9 months, and median disease-free survival was 4.6 months. 90% of patients presented recurrence. Ten of the twelve patients in the study (83.3%) died, with disease progression being the cause in eight. Of the two surviving patients, one is disease-free and the other has liver metastases. Conclusion: ASCP is a very rare pancreatic tumor with aggressive behavior. It is rarely diagnosed preoperatively. The best treatment, if feasible, is surgery followed by the standard chemotherapy regimens for pancreatic adenocarcinoma.(AU)

Introducción: El cáncer adenoescamoso de páncreas (CPAS) es un subtipo de cáncer de páncreas agresivo e infrecuente que combina un componente glandular y escamoso, y presenta baja supervivencia. Métodos: Estudio observacional retrospectivo multicéntrico realizado en tres hospitales españoles. El período de estudio fue: enero 2010 - agosto 2020. Se realizó un análisis descriptivo de los datos, así como un análisis de supervivencia global y libre de enfermedad mediante Kaplan-Meier. Resultados: De un total de 668 cánceres de páncreas tratados quirúrgicamente, doce fueron CPAS (1,8%). La edad media de los pacientes fue de 69,2±7,4 años. La proporción hombre /mujer fue de 1: 1. El síntoma principal fue la ictericia (siete pacientes). Se obtuvo un diagnóstico preoperatorio correcto en solo dos pacientes. Se realizaron nueve duodenopancretectomías cefálicas y tres pancreatoesplenectomías distales. El 25% tuvo complicaciones mayores. El tamaño medio del tumor fue de 48,6±19,4mm. Nueve pacientes recibieron quimioterapia adyuvante. La mediana de supervivencia fue de 5,9 meses y la mediana de supervivencia libre de enfermedad fue de 4,6 meses. El 90% de los pacientes presentó recidiva. Diez de los doce pacientes del estudio (83,3%) fallecieron, y la progresión de la enfermedad fue la causa en ocho. De los dos pacientes que sobrevivieron, uno está libre de enfermedad y el otro tiene metástasis hepáticas. Conclusión:El CPAS es un tumor pancreático muy raro y de comportamiento agresivo. Rara vez se diagnostica antes de la operación. El mejor tratamiento, si es posible, es la cirugía seguida de los regímenes de quimioterapia estándar para el adenocarcinoma de páncreas.(AU)

Surgical treatment of liver hydatid cyst in elderly patients: A propensity score-matching retrospective cohort study.

BACKGROUND: Cystic echinococcosis is a clinically complex chronic parasitic disease and a major socioeconomic problem in endemic areas. The safety of liver resection in elderly patients is often debated among medical professionals. We analyzed the postoperative morbidity and mortality rates of elderly patients who underwent surgery at our unit. METHODS: We retrospectively evaluated patients with liver hydatid cysts which were surgically removed at our unit. Patients were divided into two groups: Group 1 (patients < 70 years), and Group 2 (patients ≥ 70 years). Propensity score matching (PSM) and comparative analyses between groups were performed. RESULTS: The unmatched cohort consisted of 279 patients (Group 1: 244; Group 2: 35). After PSM, we compared the outcomes for 56 patients from Group 1 to 31 patients from Group 2. A higher rate of severe complications was observed in Group 2 (25.8% vs 5.36%, p = 0.014). No difference was found in the rates of infectious, cardiorespiratory, or hemorrhagic complications between both groups, and in the mortality rate either (0.00% vs 6.45%, p = 0.124). CONCLUSIONS: Liver surgery in selected elderly patients is safe and practicable. The low postoperative morbidity rate in these patients is acceptable, albeit higher, due to their comorbidities.

Prognostic value of pre-operative systemic immune-inflammation index and platelet to lymphocyte ratio in peritoneal carcinomatosis of ovarian origin.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the impact of systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) on the survival outcomes of patients who underwent to cytoreductive surgery (CRS) and HIPEC for ovarian peritoneal carcinomatosis. METHODS: A retrospective analysis of 68 cases following surgery at our department between 2015 and 2020 was performed. Receiver Operating Characteristic (ROC) curve was used with Youden index to calculate the optimal cutoff values for SII, PLR and NLR. RESULTS: Univariate analysis revealed that high preoperative values of SII, PLR and NLR were correlated with worse overall survival (OS) and disease-free survival (DFS) in these patients. In the multivariable analysis, high SII was recognized as an independent prognostic factor for OS (CI 95%: 0.002- 3.835, p = 0.097) and high PLR was recognized as an independent prognostic factor for DFS (CI 95%: 0.253-2.248, p = 0.007). CONCLUSION: SII and PLR could be useful prognostic tools to predict outcomes of patients who underwent to CRS and HIPEC for ovarian peritoneal carcinomatosis.

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID).

BACKGROUND: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. METHODS: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. RESULTS: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). CONCLUSIONS: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival.

Adenosquamous cancer of the pancreas: A multicenter retrospective study.

INTRODUCTION: Adenosquamous cancer of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. METHODS: Multicenter retrospective observational study carried out at three Spanish hospitals. The study period was: January 2010-August 2020. A descriptive analysis of the data was performed, as well as an analysis of global and disease-free survival using the Kaplan-Meier statistic. RESULTS: Of a total of 668 pancreatic cancers treated surgically, twelve were ASCP (1.8%). Patient mean age was 69.2±7.4 years. Male/female ratio was 1:1. The main symptom was jaundice (seven patients). Correct preoperative diagnosis was obtained in only two patients. Nine pancreatoduodenectomies and three distal pancreatosplenectomies were performed. 25% had major complications. Mean tumor size was 48.6±19.4mm. Nine patients received adjuvant chemotherapy. Median survival time was 5.9 months, and median disease-free survival was 4.6 months. 90% of patients presented recurrence. Ten of the twelve patients in the study (83.3%) died, with disease progression being the cause in eight. Of the two surviving patients, one is disease-free and the other has liver metastases. CONCLUSION: ASCP is a very rare pancreatic tumor with aggressive behavior. It is rarely diagnosed preoperatively. The best treatment, if feasible, is surgery followed by the standard chemotherapy regimens for pancreatic adenocarcinoma.

Implementación de un centro de referencia regional en cirugía pancreática. Experiencia tras 631 procedimientos / Implementation of a regional reference center in pancreatic surgery. Experience after 631 procedures

Introducción: El objetivo principal de este estudio es determinar si la Unidad de Cirugía Hepato-Bilio-Pancreática y Trasplante Hepático del Hospital Universitario de Badajoz cumple los estándares de calidad exigidos por la comunidad científica a los centros de referencia de cirugía pancreática (CP) en términos de resultados perioperatorios. Los objetivos secundarios consisten en comparar las diferentes técnicas de CP realizadas en función de la morbimortalidad postoperatoria precoz y analizar el impacto de las resecciones extendidas en dichos términos. Método: Estudio descriptivo, retrospectivo y unicéntrico, correspondiente al periodo 2006-2019. Se compararon los resultados obtenidos con los estándares de calidad propuestos por Bassi et al. y Sabater et al., exigidos a los centros de referencia en cirugía pancreática. La muestra se dividió según técnica quirúrgica y se compararon en términos de morbimortalidad postoperatoria precoz, estudiando el impacto de las resecciones vasculares y viscerales extendidas. Se incluyeron todos los pacientes sometidos a cirugía pancreática en nuestra unidad por patología pancreática, maligna y benigna, desde que ésta se implementó como centro de referencia. Se excluyeron las realizadas de urgencia. Resultados: Se analizaron 631 pacientes. Los valores obtenidos en los estándares de calidad se encuentran en rango. La cirugía más frecuente fue duodenopancreatectomía cefálica, la cual asoció mayor tasa de morbimortalidad perioperatoria (p ≤ 0,05). Las resecciones vasculares añadidas impactaron en el grupo de duodenopancreatectomía cefálica asociando mayor estancia media (p = 0,01) y mayor tasa de reintervención (p = 0,02). Conclusiones: La experiencia acumulada permite cumplir con los estándares de calidad exigidos, así como realizar resecciones extendidas a la pancreatectomía con buenos resultados en términos de morbimortalidad postoperatoria. (AU)

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.

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

INTRODUCTION: The main objective of this study is to determine whether 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 pancreaticoduodenectomy, which associated higher peri-operative morbidity and mortality rates (P ≤ .05). The extended vascular resections impacted the pancreaticoduodenectomy group, associating a longer mean stay (P = .01) and a higher rate of re-interventions (P = .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 morbidity and mortality.

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

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.

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

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.

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

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.

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

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.

Implementation of a regional reference center in pancreatic surgery. Experience after 631 procedures. / Implementación de un centro de referencia regional en cirugía pancreática. Experiencia tras 631 procedimientos.

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.

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

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.