Intraductal papillary mucinous neoplasm: a new entity among biliary tract neoplasms.

Biliary tract intraductal papillary mucinous neoplasms (BT-IPMN) are a rare entity that develop within the bile duct lumen and are recognized as a precursor of invasive carcinoma in up to 40-80 % of cases.

Hepatic epithelioid hemangioendothelioma: a rare vascular tumor with an unpredictable diagnosis.

We present the case of a 58-year-old female with no relevant medical or surgical history, who was referred to our hospital with a solitary hepatic lesion. She presented a slightly abnormal liver function in a routine blood test: ALT 71 U/l (range 0-33), AST 40 U/l (range 0-32) and GGT 71 U/l (range 0-40), with no symptoms. Ultrasound imaging showed a 3-cm-size focal lesion with a peripheral hypoechoic rim in the right hepatic lobe. Abdominal computed tomography (CT) scan after contrast injection revealed a subcapsular hypodense lesion in segment VII with capsular retraction. Other extrahepatic lesions were not seen.

Villous adenoma of the choledocho: an infrequent pathology of the main bile duct.

We present the case of a patient with obstructive jaundice due to a polylobulated lesion at the middle common bile duct that is identified as a villous adenoma of the main bile duct. This entity is infrequent with few references in the bibliography. It is a benign pathology but with risk of malignancy, so the diagnosis and resection is essential for adequate treatment.

Lower gastrointestinal bleeding as a form of presentation in an adult case of Abernethy syndrome.

We report the case of a 29-year-old patient who presented with a short history of lower gastrointestinal bleeding. A diagnosis of Abernethy syndrome was made (congenital extrahepatic portosystemic shunt) after this uncommon clinical presentation. The prevalence of this congenital malformation is very low and usually manifests during the pediatric age, according to previously published reports.

[Multicentre study on hepatic adenomas]. / Estudio multicéntrico sobre adenomas hepáticos.

INTRODUCTION: Hepatic adenomas (HA) are benign tumours which can present serious complications, and as such, in the past all were resected. It has now been shown that those smaller than 3 cm not expressing ß-catenin only result in complications in exceptional cases and therefore the therapeutic strategy has been changed. MATERIAL AND METHOD: Retrospective study in 14 HPB units. INCLUSION CRITERIA: patients with resected and histologically confirmed HA. STUDY PERIOD: 1995-2011. RESULTS: 81 patients underwent surgery. Age: 39.5 years (range: 14-75). Sex: female (75%). Consumption of oestrogen in women: 33%. Size: 8.8 cm (range, 1-20 cm). Only 6 HA (7.4%) were smaller than 3 cm. The HA median was 1 (range: 1-12). Nine patients had adenomatosis (>10HA). A total of 51% of patients displayed symptoms, the most frequent (77%) being abdominal pain. Eight patients (10%) began with acute abdomen due to rupture and/or haemorrhage. A total of 67% of the preoperative diagnoses were correct. Surgery was scheduled for 90% of patients. The techniques employed were: major hepatectomy (22%), minor hepatectomy (77%) and one liver transplantation. A total of 20% were performed laparoscopically. The morbidity rate was 28%. There were no cases of mortality. Three patients had malignisation (3.7%). The follow-up period was 43 months (range 1-192). Two recurrences were detected and resected. DISCUSSION: Patients with resected HA are normally women with large lesions and oestrogen consumption was lower than expected. Its correct preoperative diagnosis is acceptable (70%). The major hepatectomy rate is 25% and the laparoscopy rate is 20%. There was a low morbidity rate and no mortality.

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma.

The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.

Functional Characterisation of Bile Metagenome: Study of Metagenomic Dark Matter.

Gallbladder metagenome involves a wide range of unidentified sequences comprising the so-called metagenomic dark matter. Therefore, this study aimed to characterise three gallbladder metagenomes and a fosmid library with an emphasis on metagenomic dark matter fraction. For this purpose, a novel data analysis strategy based on the combination of remote homology and molecular modelling has been proposed. According to the results obtained, several protein functional domains were annotated in the metagenomic dark matter fraction including acetyltransferases, outer membrane transporter proteins, membrane assembly factors, DNA repair and recombination proteins and response regulator phosphatases. In addition, one deacetylase involved in mycothiol biosynthesis was found in the metagenomic dark matter fraction of the fosmid library. This enzyme may exert a protective effect in Actinobacteria against bile components exposure, in agreement with the presence of multiple antibiotic and multidrug resistance genes. Potential mechanisms of action of this novel deacetylase were elucidated by molecular simulations, highlighting the role of histidine and aspartic acid residues. Computational pipelines presented in this work may be of special interest to discover novel microbial enzymes which had not been previously characterised.

Ventral Portal Vein Over Gallbladder and Pancreas---An Exceptional Anatomical Variation Found in a Liver Transplant Patient: A Case Report.

BACKGROUND: Anatomic variations are well known in the liver hilum. A rare precholecystic, preduodenal, prepancreatic portal vein is described as found in a liver transplant candidate. Precholecystic location of portal vein is an exceptional finding and does not seem to have been previously described. It is associated with a preduodenal portal vein. Its position is challenging, as its surface can be mistaken with the gallbladder wall. We present the case of a patient candidate to liver transplantation. In the preoperative studies, a portal thrombosis was suspected, with recanalization by collaterals, but also a malformation was suggested. The patient had a primary biliary cirrhosis. Other findings included agenesis of inferior vena cava on the right side. During operation, the portal vein was found over the gallbladder and fixed to it, making it at first difficult to distinguish one from the other. CONCLUSIONS: A precholecystic portal vein is a rare finding that poses a challenge for the surgeon. It must be ruled out in the preoperative workout.

The human gallbladder microbiome is related to the physiological state and the biliary metabolic profile.

BACKGROUND: The microbial populations of the human intestinal tract and their relationship to specific diseases have been extensively studied during the last decade. However, the characterization of the human bile microbiota as a whole has been hampered by difficulties in accessing biological samples and the lack of adequate methodologies to assess molecular studies. Although a few reports have described the biliary microbiota in some hepatobiliary diseases, the bile microbiota of healthy individuals has not been described. With this in mind, the goal of the present study was to generate fundamental knowledge on the composition and activity of the human bile microbiota, as well as establishing its potential relationship with human bile-related disorders. RESULTS: Human bile samples from the gallbladder of individuals from a control group, without any record of hepatobiliary disorder, were obtained from liver donors during liver transplantation surgery. A bile DNA extraction method was optimized together with a quantitative PCR (qPCR) assay for determining the bacterial load. This allows the selection of samples to perform functional metagenomic analysis. Bile samples from the gallbladder of individuals suffering from lithiasis were collected during gallbladder resection and the microbial profiles assessed, using a 16S rRNA gene-based sequencing analysis, and compared with those of the control group. Additionally, the metabolic profile of the samples was analyzed by nuclear magnetic resonance (NMR). We detected, for the first time, bacterial communities in gallbladder samples of individuals without any hepatobiliary pathology. In the biliary microecosystem, the main bacterial phyla were represented by Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Significant differences in the relative abundance of different taxa of both groups were found. Sequences belonging to the family Propionibacteriaceae were more abundant in bile samples from control subjects; meanwhile, in patients with cholelithiasis members of the families Bacteroidaceae, Prevotellaceae, Porphyromonadaceae, and Veillonellaceae were more frequently detected. Furthermore, the metabolomics analysis showed that the two study groups have different metabolic profiles. CONCLUSIONS: Our results indicate that the gallbladder of human individuals, without diagnosed hepatobiliary pathology, harbors a microbial ecosystem that is described for the first time in this study. Its bacterial representatives and metabolites are different from those detected in people suffering from cholelithiasis. In this regard, since liver donors have been subjected to the specific conditions of the hospital's intensive care unit, including an antibiotic treatment, we must be cautious in stating that their bile samples contain a physiologically normal biliary microbiome. In any case, our results open up new possibilities to discover bacterial functions in a microbial ecosystem that has not previously been explored.

Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations.

CONTEXT: SDHB mutations are found in an increasing number of neoplasms, most notably in paragangliomas and pheochromocytomas (PPGLs). SDHB-PPGLs are slow-growing tumors, but ∼50% of them may develop metastasis. The molecular basis of metastasis in these tumors is a long-standing and unresolved problem. Thus, a better understanding of the biology of metastasis is needed. OBJECTIVE: This study aimed to identify gene methylation changes relevant for metastatic SDHB-PPGLs. DESIGN: We performed genome-wide profiling of DNA methylation in diverse clinical and genetic PPGL subtypes, and validated protocadherin γ-C3 (PCDHGC3) gene promoter methylation in metastatic SDHB-PPGLs. RESULTS: We define an epigenetic landscape specific for metastatic SDHB-PPGLs. DNA methylation levels were found significantly higher in metastatic SDHB-PPGLs than in SDHB-PPGLs without metastases. One such change included long-range de novo methylation of the PCDHA, PCDHB, and PCDHG gene clusters. High levels of PCDHGC3 promoter methylation were validated in primary metastatic SDHB-PPGLs, it was found amplified in the corresponding metastases, and it was significantly correlated with PCDHGC3 reduced expression. Interestingly, this epigenetic alteration could be detected in primary tumors that developed metastasis several years later. We also show that PCDHGC3 down regulation engages metastasis-initiating capabilities by promoting cell proliferation, migration, and invasion. CONCLUSIONS: Our data provide a map of the DNA methylome episignature specific to an SDHB-mutated cancer and establish PCDHGC3 as a putative suppressor gene and a potential biomarker to identify patients with SDHB-mutated cancer at high risk of metastasis who might benefit from future targeted therapies.

Mismatch repair protein MSH2, cytokeratin 18 and cytokeratin 20 expression: clinicopathological correlation and prognostic value in colorectal cancer patients.

BACKGROUND/AIMS: The survival of patients with colorectal cancer has not varied appreciably in recent years. The knowledge that genetic factors and disruption in apoptosis could play a role in the etiology and prognosis of patients with sporadic colorectal cancer has opened up new lines of research. We have studied a group of patients with colorectal cancer and the possible influence on the prognosis of immunohistochemical MSH2, M30 cytodeath and cytokeratin 20 expression. METHODOLOGY: Forty-nine consecutive patients with unselected colorectal cancer treated by resection and with a minimum follow-up period of 5 years. Tumor specimens were evaluated by an inmunohistochemical method for MSH2, cytokeratin 18 (M30 cytodeath) and cytokeratin 20 expression and correlated with epidemiological, clinicopathological and survival data. RESULTS: Thirty-four patients were resected with curative intention. At the end of the follow-up period, 25 (51%) had died, the majority (21) in relation to tumor progression, the overall median survival period being 47.9 months (95% CI = 27-86.6). Only vascular invasion, (lower median values), (p = 0.04) was related to MSH2 expression and tumor stage (p = 0.02) with cytokeratin 20. Patients' survival was related to tumoral stage (p = 0.04) and vascular invasion (p = 0.002). MSH2 expression, apoptosis (M30 cytodeath) and cytokeratin 20 staining did not influence the prognosis of patients. CONCLUSIONS: A change in the percentage of tumoral staining cells for MSH2, M30 cytodeath and cytokeratin 20 is frequent in patients with colorectal cancer. Only vascular invasion was correlated with MSH2 expression and stage of disease with cytokeratyn 20. Survival was related to TNM stage and vascular invasion, but not to MSH2, M30 cytodeath or cytokeratin 20 expressions.

Inflammatory pseudotumor of spleen: a case report.

INTRODUCTION: Inflammatory pseudotumor of spleen is an extremely rare benign condition of uncertain etiology that presents with nonspecific symptoms or as an incidental finding in patients studied by other processes. Since the first description in 1984 by Cotelingam and Jaffe, only 114 cases have been reported. PRESENTATION OF CASE: We present a case of a fifty-six years old woman with a splenic injury in ultrasound and computed tomography. The patient undergoes laparoscopic splenectomy and the histologic study of the specimen revealed findings consistent with inflammatory pseudotumor of spleen. DISCUSSION: This rare entity whose pathogenesis is still unknown, can present with nonspecific symptoms. Radiologic studies may lead the diagnosis being useful CT and MRI. The definitive diagnosis is established with the histological findings, characterized by the presence of inflammatory cells with areas of necrosis and fibrosis. There are multiple differentials diagnoses: metastasis, lymphoma, splenic infarction, hemangiomas, vascular malformations, lymphangioma, plasmacytoma, reactive lymphoid hyperplasia, abscess and infectious granulomatous processes; therefore suspicion of malignant neoplasm must be considered, being indicated splenectomy to confirm the diagnosis. CONCLUSION: Inflammatory pseudotumor of spleen is a benign disease, in which diagnostic approach must bear in mind the possibility of a malignant lesion. For this reason, the surgical approach is appropriate to confirm the diagnosis and rule out malignancy with histology.

Glucagonoma syndrome: a case report.

INTRODUCTION: Glucagonoma syndrome is a rare paraneoplastic phenomenon, with an estimated incidence of one in 20 million, characterized by necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, cheilitis, steatorrhea, diarrhea, venous thrombosis and neuropsychiatric disturbances in the setting of a glucagon-producing alpha-cell tumor of the pancreas. Necrolytic migratory erythema is the presenting manifestation in the majority of cases, so its early suspicion and correct diagnosis is a key factor in the management of the patient. CASE PRESENTATION: We present the case of a 70-year-old Caucasian woman with glucagonoma syndrome due to an alpha-cell tumor located in the tail of the pancreas, successfully treated with surgical resection. CONCLUSION: Clinicians should be aware of the unusual initial manifestations of glucagonoma. Early diagnosis allows complete surgical resection of the neoplasm and provides the only chance of a cure.

Treatment of Liver Trauma: Operative or Conservative Management.

BACKGROUND: The liver is one of the most frequently damaged organs when abdominal trauma occurs. Currently, a conservative management constitutes the treatment of choice in patients with hemodynamic stability. The aim of this study is to evaluate the results of an operative and conservative management of 143 patients with liver injury treated in a single institution. METHODS: A retrospective study of the patients admitted with the diagnosis of liver trauma was performed from 1992-2008. The patients were classified according to the intention to treatment: Group I, operative management; Group II, conservative management. Variables analyzed included demographic data, injury classification, associated lesions, surgical treatment, transfusions, morbi-mortality, and hospital stay. We established two periods (1992-1999; 2000-2008) in order to compare diagnosis and management. RESULTS: A total of 143 patients were analyzed. Thirty-one percent correspond to severe injuries. Conservative treatment was followed in 60.8 % with surgery undertaken in 14.9 % of patients from this group due to failure of conservative treatment. Immediate surgery was carried out in 38.2 %. Total mortality was 14 %. Morbidity (35.7-38.5 %) in the group of immediate surgery and failure of conservative management is similar, but not in mortality (28.6-15.4 %). In the second group (2000-2008) there are more patients with conservative treatment, with a low percentage of failure of this treatment and morbi-mortality. CONCLUSIONS: Conservative treatment is an adequate treatment in a great number of patients. Failure of conservative treatment did not show a higher incidence of complications or mortality but it should be performed in centers with experienced surgeons.

[Obesity in the history of surgery]. / La obesidad en la historia de la cirugía.

Obesity is a problem that is reaching epidemic proportions throughout the world and bariatric surgery is now a rapidly growing technique. However existence of obesity in humans has been recognized for thousands of years, as statues dating from the Stone Age period appear to provide the earliest depictions. Hippocrates (466-355 b.C.) and Galen (131-201 a.C.) had a clear understanding of the condition, its consequences and medical treatment. On the other hand bariatric surgery was a xx century treatment, but at the end of the xix century it was known that the massive loss of small bowel or gastric resection after ulcer surgery resulted in persistent weight loss. Malabsorption and gastric restriction in isolation, or more commonly in combination, remain the main options to surgical control of weight. Unfortunately surgery as a non etiological treatment is an imperfect model to treat an incurable disease: morbid obesity. Prevention and better knowledge of disease would allow a tailored medical or surgical approach.