Neuroendocrine tumours of the ampulla of Vater: clinico-pathological features, surgical approach and assessment of prognosis

BACKGROUND/AIMS: Neuroendocrine tumours occur very rarely in the ampulla of Vater and their clinical behaviour is unknown. The aim of this study is to assess the clinico-pathological features, surgical approach and prognosis of these patients. METHODS: Six patients with neuroendocrine tumours of the ampulla of Vater treated with curative intent surgery at a single centre were retrospectively analysed. A univariate analysis of potential prognostic factors was also performed (data provided from the present study and literature review). RESULTS: Pancreaticoduodenectomy was curative in all the patients. Overall and disease-free survival rates were significantly better for G1/G2 tumours (p = 0.006 and p = 0.004, respectively). Although frequent, lymph node metastases did not influenced both overall (p = 0.760) and disease-free survival rates (p = 0.745). No significant differences of survival were observed in patients with ENETS stage I/II disease, as compared to ENETS stage III disease (p = 0.169 and p = 0.137, respectively). No differences were observed according to UICC staging system (p = 0.073 and p = 0.177, respectively). Tumours that are less than 2 cm or limited to the ampulla appear to have a better prognosis. CONCLUSION: The WHO 2010 classification appear to accurately predict patient prognosis, while the ENETS or UICC staging systems have a limited value (especially in regard to lymph node metastases). Radical surgery (i.e. pancreaticoduodenectomy with lymphadenectomy) should be the standard approach in most patients with NET of the ampulla of Vater because this procedure removes all the potential tumour-bearing tissue

Diagnostic and Therapeutic Challenges in Nonparasitic Liver Cysts

Nonparasitic hepatic cysts constitute a heterogeneous group of disorders. A proper diagnosis of hepatic cyst is necessary in order to adopt the best treatment. The term hepatic cyst usually refers to simple hepatic cysts. Nonparasitic hepatic cysts are also linked to genetic disorders such as polycystic liver disease (PLD) with/without autosomal dominant polycystic kidney disease (ADPKD) or Caroli disease. Generally, patients with nonparasitic hepatic cysts less than 3 cm are asymptomatic. These cysts become symptomatic when are large, multiple, or complicated. Percutaneous abdominal ultrasound is the best imaging modality to diagnose hepatic cysts but must be completed by other imaging and serological tests. It is important to differentiate simple hepatic cyst from hydatid cyst, cystadenoma, and cystadenocarcinoma before proceeding with the treatment. Sometimes the diagnosis is very challenging. Asymptomatic single liver cysts need only surveillance, but symptomatic and complicated ones require therapeutic intervention. Percutaneous aspiration of the cyst under ultrasound guidance is a mini-invasive procedure generally associated with sclerotherapy. The highest success rates were reported for laparoscopic or open cyst fenestration. Liver transplantation is indicated for patients with severe PLD

Challenging Issues in Hepatic Adenoma

Hepatic adenoma is known as a benign lesion encountered mainly in female patients and classically linked to the administration of oral contraceptives. In the last decade, the risk factors for its occurrence have changed and so did the sex ratio. The histopathological classification of hepatic adenomas was found to be related with certain genetic mutations that determine the risk for malignancy. The diagnosis of hepatic tumor is correlated with clinical and imaging data in an effort not only to rule out other tumors but also to distinguish the subtype of adenoma, which is very important for the management of the patient. The ultimate diagnosis is established by pathologists by routine histopathological and specific immunohistochemical staining. There are two major issues that pathologists need to recognize: the presence of β-catenin gene mutation and/or malignant degeneration. The best imaging examination is considered to be MRI. However, along with MRI, ultrasound and computer tomography have proved themselves to be effective not only in evaluating the number, size, localization, and complications of hepatic adenomas, but also in identifying their subtype. A detailed presentation of characteristics of all groups of hepatic adenoma is provided. The means of management of hepatic adenomas are documented and decisional algorithm is explained, based on certain criteria

Transplantul hepatic ortotopic de la donator decedat la adult. Experienţa Centrului de Chirurgie Generală şi transplant hepatic Fundeni

Studiul de faţă analizează experienţa Centrului de Chirurgie Generală şi Transplant Hepatic din Institutul Clinic Fundeni în transplantul hepatic ortotopic cu ficat întreg de la donator decedat la adult (THO), din aprilie 2000 până în aprilie 2006. În această perioadă au fost realizate 45 de THO – 20 femei şi 25 de bărbaţi, cu vârste cuprinse între 19-57 de ani (medie de 45 ani).Indicaţiile pentru transplantare au fost: ciroză VHB – 11, ciroză VHB VHD – 6, ciroză VHC – 13 (2 cu hepatocarcinom), ciroză VHB VHC – 2, ciroză VHB VHD etanol – 1, ciroză biliară primitivă – 5, boala Wilson – 2, ciroză toxic-nutriţională – 2, ciroza toxică non-alcoolică – 1, ciroză autoimună – 1, colangită sclerogenă primitivă – 1. Cu trei excepţii, la care s-a folosit tehnica clasică de transplantare, ficatul a fost grefat după tehnica Belghiti. Complicaţiile postoperatorii locale au survenit la 19 bolnavi (42,22%), iar generale la 19 (42,22%); complicaţiile tardive au fost înregistrate la 20 pacienţi (44,44%), iar recidiva bolii la 7 pacienţi (15,55%). Mortalitatea intraoperatorie şi postoperatorie imediată a fost de 6,66% (3 din 45 pacienţi). La peste 30 de zile de la TH, au decedat alţi cinci pacienţi (11,11%). Patru pacienţi (8,88%) au decedat la distanţă de momentul transplantului prin boală venoocluzivă, prin cancer bronho-pulmonar şi prin infarct miocardic -2. Patruzeci si doi de pacienţi au supravieţuit perioadei postoperatorii (93,33%) şi 33 peste un an (73,33%). THO reprezintă metoda principală de transplantare hepatică, cu o morbiditate şi mortalitate acceptabile

Insights into Epigenetic Changes Related to Genetic Variants and Cells-of-Origin of Pancreatic Neuroendocrine Tumors: An Algorithm for Practical Workup

Current knowledge on the molecular landscape of pancreatic neuroendocrine tumors (PanNETs) has advanced significantly. Still, the cellular origin of PanNETs is uncertain and the associated mechanisms remain largely unknown. DAXX/ATRX and MEN1 are the three most frequently altered genes that drive PanNETs. They are recognized as a link between genetics and epigenetics. Moreover, the acknowledged impact on DNA methylation by somatic mutations in MEN1 is a valid hallmark of epigenetic mechanism. DAXX/ATRX and MEN1 can be studied at the immunohistochemical level as a reliable surrogate for sequencing. DAXX/ATRX mutations promote alternative lengthening of telomeres (ALT) activation, determined by specific fluorescence in situ hybridization (FISH) analysis. ALT phenotype is considered a significant predictor of worse prognosis and a marker of pancreatic origin. Additionally, ARX/PDX1 expression is linked to important epigenomic alterations and can be used as lineage associated immunohistochemical marker. Herein, ARX/PDX1 association with DAXX/ATRX/MEN1 and ALT can be studied through pathological assessment, as these biomarkers may provide important clues to the mechanism underlying disease pathogenesis. In this review, we present an overview of a new approach to tumor stratification based on genetic and epigenetic characteristics as well as cellular origin, with prognostic consequences

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC

Circulating Angiogenic Markers in Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review

Background: Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no biomarker has showed satisfying accuracy in predicting outcome or response to treatment. Methods: We conducted a systematic review to determine relevant circulating biomarkers for angiogenesis in neuroendocrine tumors. We searched three databases (Pubmed, Embase, Web of Science) using the keywords “neuroendocrine” and “biomarkers”, plus specific biomarkers were searched by full and abbreviated name. From a total of 2448 publications, 11 articles met the eligibility criteria. Results: VEGF is the most potent and the most studied angiogenic molecule, but results were highly controversial. Placental growth factor, Angiopoietin 2 and IL-8 were the most consistent markers in predicting poor outcome and aggressive disease behavior. Conclusions: There is no robust evidence so far to sustain the use of angiogenic biomarkers in routine practice, although the results show promising leads

A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Renal involvement is a frequent complication of systemic lupus erythematosus (SLE). It occurs in up to two-thirds of patients, often early during the disease course, and is the most important predictor of the morbidity and mortality of SLE patients. Despite tremendous improvements in the approach of the lupus nephritis (LN) therapy, including the recent approval of two new disease-modifying therapies, up to 50% of patients do not obtain a renal response and up to 25% will eventually progress to end-stage renal disease (ESRD) within 10 years of diagnosis. Given the lack of correlation between clinical features and histological lesions, there is an increasing need for a histology-guided approach to the management of patients with LN. Apart from the initial diagnosis of type and severity of renal injury in SLE, the concept of a repeat kidney biopsy (either in a for-cause or a per-protocol scenario) has begun to gain increasing popularity in the nephrology community. Herein, we will provide a comprehensive overview of the most important areas of utility of the kidney biopsy in patients with LN

Comparative RNA-Sequencing Analysis Reveals High Complexity and Heterogeneity of Transcriptomic and Immune Profiles in Hepatocellular Carcinoma Tumors of Viral (HBV, HCV) and Non-Viral Etiology

Background and Objectives: Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is the leading cause of cancer-related mortality. It arises and progresses against fibrotic or cirrhotic backgrounds mainly due to infection with hepatitis viruses B (HBV) or C (HCV) or non-viral causes that lead to chronic inflammation and genomic changes. A better understanding of molecular and immune mechanisms in HCC subtypes is needed. Materials and Methods: To identify transcriptional changes in primary HCC tumors with or without hepatitis viral etiology, we analyzed the transcriptomes of 24 patients by next-generation sequencing. Results: We identified common and unique differentially expressed genes for each etiological tumor group and analyzed the expression of SLC, ATP binding cassette, cytochrome 450, cancer testis, and heat shock protein genes. Metascape functional enrichment analysis showed mainly upregulated cell-cycle pathways in HBV and HCV and upregulated cell response to stress in non-viral infection. GeneWalk analysis identified regulator, hub, and moonlighting genes and highlighted CCNB1, ACTN2, BRCA1, IGF1, CDK1, AURKA, AURKB, and TOP2A in the HCV group and HSF1, HSPA1A, HSP90AA1, HSPB1, HSPA5, PTK2, and AURKB in the group without viral infection as hub genes. Immune infiltrate analysis showed that T cell, cytotoxic, and natural killer cell markers were significantly more highly expressed in HCV than in non-viral tumors. Genes associated with monocyte activation had the highest expression levels in HBV, while high expression of genes involved in primary adaptive immune response and complement receptor activity characterized tumors without viral infection. Conclusions: Our comprehensive study underlines the high degree of complexity of immune profiles in the analyzed groups, which adds to the heterogeneous HCC genomic landscape. The biomarkers identified in each HCC group might serve as therapeutic targets

Impact of Hepatitis B Virus on Clinicopathological Features and Outcomes After Resection for Pancreatic Adenocarcinoma

Part of the data were presented at the International Symposium for Pancreatic Cancer 2014 (July 3-5, 2014, Verona, Italy).International audienceBackground/ Aim: Chronic hepatitis B virus (HBV) infection is sometimes considered a risk factor for pancreatic cancer (PDAC), but the prognostic value of its presence has only rarely been investigated. The present study aimed to explore the impact of HBV after resection for PDAC. Materials and Methods: According to HBV surface antigen seroreactivity, 343 patients were classified as having non-viral or HBV-related cases of PDAC. Clinicopathological data and outcomes were comparatively assessed between the groups. Results: Chronic HBV infection was observed in 16 patients (4.5%). No significant differences between the HBV and non-viral cases of PDAC were observed. Tumor diameters (3.4 vs. 3.0, p=0.092) and stages at diagnosis (31 vs. 14% T1-T2, p=0.082) tended to differ between the groups, albeit without reaching significance. Completion of adjuvant therapy (63 vs. 54%, p=0.612), as well as median overall survival (15 vs. 17 months, p=0.346) was similar in the HBV and non-viral PDAC groups. Conclusion: HBV-positive and virus-free patients with PDAC generally shared the same demographic, clinical and pathological profiles. HBV did not appear to have a detrimental effect on either early or long-term outcomes after resection for PDAC. Future studies searching for occult infection might, however, shed a different light on the role of HBV in PDAC