Publications by authors named "Diego Lopez-Guerra"

17 Publications

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hospital Universitario de Badajoz, Badajoz, España.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hepatic abscess caused by a fishbone: An unusual finding.

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

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

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

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

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

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

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

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

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

Hospital Infanta Cristina. Badajoz.

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

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

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

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

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

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

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

[Bezoar after ingestion of metallic foreign bodies].

Cir Cir 2011 Sep-Oct;79(5):464-7

Servicio de Cirugía General y del Aparato Digestivo, Hospital Infanta Cristina, Badajoz, España.

Background: Ingestion of foreign bodies represents a common feature in psychiatric patients and prisoners. Bezoar is a conglomeration of partially or undigested foreign material in the gastrointestinal tract. These are classified into several types according to the materials which they are composed of, the least frequent being metals. There are few cases reported in the literature.

Clinical Case: We report a case of a patient with a pathological history of mental disorder. The patient complained of abdominal pain 24 h prior, and there were no other symptoms. Physical examination revealed pain in the upper quadrant without peritoneal irritation. Laboratory tests were normal and plain x-ray of the abdomen showed several metallic foreign bodies, some sharp, >5 cm in length and with intestinal prolongation. Surgical intervention was performed several hours later: gastrotomy to remove the gastric bezoar that was composed of several screws, nails, scrap metal, lighters, clothespins, radio antennas and one coin. Four metallic foreign bodies were found in the small bowel after reviewing the abdominal cavity, so enterotomy was also performed to remove them. Postoperative course was uneventful.

Conclusions: Surgical treatment must be considered in cases of multiple, large, sharp objects or complications. An exhaustive study of the case is essential to avoid delay in treatment and potential complications.
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July 2012