Nikolaos Vassos

Coexistence of gastrointestinal stromal tumours (GIST) and malignant neoplasms of different origin: Prognostic implications

BACKGROUND Over the past decade, several changes occurred in diagnostics, treatment and understanding of pathogenesis of gastrointestinal stromal tumours (GIST). However, their coexistence with other malignancies of different histogenetic origin remains a challenging issue. METHODS Patients diagnosed with GIST in a 10-years period were identified retrospectively and clinical history and findings thoroughly explored for the presence of associated other malignancies. Follow up data were obtained and analysed for prognostic impact of the concurrent malignancy and/or GIST. RESULTS Thirty seven (27 males, 10 females) of 86 GIST-patients (43%) had another malignancy. Mean age was 70 years. Associated malignancies were gastrointestinal (n = 29; 69%), renal-/urological (n = 5; 12%), haematological (n = 4; 9.5%), cutaneous (n = 3; 7%) and thyroid (n = 1; 2.5%) in origin. Majority of GISTs occurred in stomach (65%) and small intestine (30.6%) and most (78%) were asymptomatic incidental findings during diagnostic or therapeutic procedures for associated malignancies. GIST size ranged from 0.1 cm to 9 cm (mean, 2.2 cm) and all of them had a low (<5/50 HPFs) or no mitotic activity. Thirty-one tumours (84%) were of no/very low/low risk and 6 were of intermediate risk. During follow-up (range 3-160 months, mean; 60 months), one patient suffered from distant metastases of GIST. Seven patients (19%) died of associated malignancies and three patients (8%) of other non-tumour-associated cause, but none died of GIST. CONCLUSION Coexistence of GIST with other malignancies is higher than previously reported and should draw attention of clinicians towards these incidental findings. Prognosis in these patients is usually determined by other malignancy and not significantly influenced by GIST. Therefore treatment algorithms should be focused on prognostically relevant malignancy.

MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma

Objective Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases. Methods We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE) tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR. Results All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01). MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01). No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01). Conclusion In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

A novel complex KIT mutation in a gastrointestinal stromal tumor of the vermiform appendix

Gastrointestinal stromal tumors of the vermiform appendix are rare. To date, only 11 cases have been reported in the English literature. Here, we present a new case of appendiceal gastrointestinal stromal tumor associated with complete situs inversus. A 48-year-old man was operated on due to appendicitis-like symptoms. Laparotomy revealed a ruptured conglomerate tumor in the lower abdomen associated with extensive peritoneal adhesions. Histology showed a spindle cell gastrointestinal stromal tumor with prominent sclerosis and calcification without low mitotic activity. The tumor cells expressed strongly CD117 and CD34. The mutation analysis revealed a heterozygous deletion/insertion involving exon 11 of KIT (pK558_V559delNNins). Because the tumor was ruptured intraoperatively, a high risk was assigned according to the revised National Institute of Health criteria and adjuvant therapy with imatinib mesylate was recommended. The patient is currently alive without evidence of progression 27 months after surgery.

What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the Liver. Is There Any Place for Surgery

Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.

Prognostic and diagnostic value of procalcitonin in the post-transplant setting after liver transplantation

Introduction The aim of the study was to assess the diagnostic accuracy of procalcitonin (PCT) as a marker for complications and as a prognostic factor for mortality after liver transplantation. Material and methods Liver transplant patients between January 2007 and April 2011 were prospectively included in the study. Procalcitonin serum concentration was recorded before, 6 h after reperfusion and then daily. Postoperative clinical course was prospectively analyzed from admission to discharge. Main surgical data such as operating procedure, type of reperfusion, operating and ischemic times, high urgency (HU) status and MELD score at the time of transplantation were also recorded. Results Sixteen patients with initial PCT > 5 ng/ml suffered ≥ 1 complication (p = 0.03). However, there was no association between the level of the 1st peak PCT and the further postoperative course or the occurrence of complications. Patients in whom a 2nd PCT peak occurred had a significantly higher risk for a complicated course, for a complicated sepsis course and for mortality (p < 0.0001). Warm ischemic time over 58 min, operating time over 389 min and HU status were significant independent factors for a complicated postoperative course (p < 0.001, p < 0.001 and p = 0.03 respectively). Conclusions Based on our results, we believe that PCT course and the occurrence of a 2nd peak seem to possess important diagnostic and prognostic power in the post-transplant setting after liver transplantation.

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine‐mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10−04) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10−09). On chromosome 5p13 we found cis‐eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10−11). On chromosome 8q24 we observed cis‐eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10−47). In addition, we found trans‐eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10−09). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk‐conferring GC pathomechanisms.

Intra-abdominal localized hyaline-vascular Castleman disease: imaging characteristics and management of a rare condition.

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology and one of the uncommon causes of nonneoplastic lymphadenopathy. Earlier synonyms of CD included angiofollicular lymph node hyperplasia, giant lymph node hyperplasia, lymphoid hamartoma, benign lymphoma and follicular lymphoreticuloma. This disease was first reported by Castleman et al. in 1954 [1] and later defined by Castleman et al. in 1956 in a series of 13 patients with unicentric hyaline vascular CD presenting with large thymoma-like masses in the anterior mediastinum [2]. The condition was later found to be occasionally associated with hypochromic anemia, hypergammaglobulinemia and bone marrow plasmacytosis [3, 4]. By the late 1960s and the early 1970s, the histological features of the different forms of the disease and the classification in current use had been established [5, 6]. The disease features three main histopathological presentations: hyaline vascular, plasma cell-rich, and mixed variants [6, 7]. The exact incidence of CD is unknown. Association of certain forms of the disease with the human immunodeficiency virus (HIV) and human herpes virus-8 (HHV-8) infections has been long recognized. In 1985, Lachant et al. reported on 2 patients with the acquired immunodeficiency syndrome (AIDS) who developed multicentric CD followed by Kaposi sarcoma [8]. In 1995, Soulier et al. reported frequent coincidence of HHV-8 in 31 patients with multicentric CD [9].