Genomic and genetic alterations influence the progression of gastric cancer

Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.

Biliary tree gastrinomas in multiple endocrine neoplasia type 1 syndrome

AIM:To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic.METHODS:Between January 1992 and June 2012,28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1(MEN1)syndrome underwent surgery at our institution.This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome(ZES).Surgical treatment consisted of duodenopancreatectomy(DP)or total pancreatectomy(TP).Regional lymphadenectomy was always performed.Any hepatic tumoral lesions found were removed during surgery.In MEN1 patients,removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia.One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors.This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree.RESULTS:Seventeen MEN1 patients affected with ZES were analyzed.The mean age was 40 years.Fifteen patients underwent DP and two TP.On histopathological examination,duodeno pancreatic endocrine tumors were found in all 17 patients.Eighty-one gastrinomas were detected in the first three portions of the duodenum.Only one gastrinoma was found in the pancreas.The mean number of gastrinomas per patient was 5(range 1-16).Malignancy was established in 12 patients(70.5%)after lymph node,liver and omental metastases were found.Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s).In two cases,the ectopic gastrinoma was removed at the same time as pancreatic surgery,while in the third case,the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES.CONCLUSION:These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery.

Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis(FAP) and any relationship with epithelial proliferation/apoptosis markers.METHODS: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression(labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low(LGD)and high-grade dysplasia(HGD), adenocarcinoma(AC). One-way analysis of variance, corrected by Bonferroni's test, and Pearson's correlation test were applied for statistical analysis.RESULTS: ER-beta showed a progressive decline: normal tissue(23.5 ± 4.9), LGD(21.1 ± 4.8), HGD(9.3 ± 3.5), AC(7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls(23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue(24.8 ± 5.6) to AC(52.0 ± 8.2); the expression in normal tissue was similar to controls(22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson's correlation test showed a direct relationship between ER-b and TUNEL LI(r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI(r =- 0.7257, P < 0.0001). The co-expression of ER-b and caspase 3 declined progressively from normal to neoplastic tissue.CONCLUSION: This study confirmed that ER-b is strongly decreased in duodenal FAP carcinomas, declining in a multiple step fashion, thereby suggesting a putative anti-carcinogenic effect. ER-α showed the opposite trend. ER-b/caspase 3 co-expression suggests this hormone's possible involvement in apoptosis. Hormonal influences in FAP duodenal tumorigenesis, and modulation of these as a possible chemoprevention strategy, may be a promising approach.

Peripancreatic paraganglioma:Lesson from a round table

We described the case of a peripancreatic paraganglioma(PGL)misdiagnosed as pancreatic lesion.Surgical exploration revealed an unremarkable pancreas and a large well-defined cystic mass originating at the mesocolon root.Radical enucleation of the mass was performed,preserving the pancreatic tail.Histologically,a diagnosis of PGL was rendered.Interestingly,two previously unreported mutations,one affecting the KDR gene in exon 7 and another on the JAK3 gene in exon 4 were detected.Both mutations are known to be pathogenetic.Imaging and cytologic findings were blindly reviewed by an expert panel of clinicians,radiologists,and pathologists to identify possible causes of the misdiagnosis.The major issue was lack of evidence of a cleavage plane from the pancreas at imaging,which prompted radiologists to establish an intraparenchymal origin.The blinded revision shifted the diagnosis towards an extrapancreatic lesion,as the pancreatic parenchyma showed no structural alterations and no dislocation of the Wirsung duct.Ex post,the identified biases were the emergency setting of the radiologic examination and the very thin mesocolon sheet,which hindered clear definition of the lesion borders.Original endoscopic ultrasonography diagnosis was confirmed,emphasizing the intrinsic limit of this technique in detecting large masses.Finally,pathologic review favored a diagnosis of PGL due to the morphological features and immonohistochemical profile.Eighteen months after tumor excision,the patient is asymptomatic with no disease relapse evident by either radiology or laboratory tests.Our report strongly highlights the difficulties in rendering an accurate preoperative diagnosis of PGL.

A New Early Gastric Cancer after Subtotal Gastric Resection for Early Cancer: Case Report and Review of the Literature

Although the prognosis of early gastric cancer (EGC) is considered to be satisfactory, some patients experience tumor relapse after curative surgery. Both pathogenesis and risk factors of recurrence remain unclear. We describe a case report of a 49-year-old male who underwent subtotal gastric resection D2A for angular gastric cancer. Histological examination revealed gastric adenocarcinoma with low grade of differentiation and colloid areas, intramucosal, and absence of neoplastic proliferation in the surgical margins, in omental stroma and in the six examined lymph nodes (pT1, pN0). 11 years later, the same patient underwent D2 total gastrectomy for gastric cancer in the remnant stomach. New histological examination revealed again gastric adenocarcinoma, intramucosal, medium degree of differentiation, no documentable neoplastic proliferation within the limits of surgical resection, in the thirty-three examined lymph nodes and in the omentum (pT1, pN0).