Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours: analyses according to the WHO 2010 classification.

OBJECTIVE: Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications. MATERIAL AND METHODS: One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated. RESULTS: Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate. CONCLUSION: Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery.

Combination of hepatocellular markers is useful for prognostication in gastric hepatoid adenocarcinoma.

Hepatoid or α-fetoprotein (AFP)-producing adenocarcinomas of stomach growing in a solid pattern are highly aggressive tumors. It is difficult to detect hepatoid differentiation solely based on findings from hematoxylin and eosin stainings, especially in small biopsy specimens. Gastric adenocarcinomas with hepatoid differentiation should be distinguished from solid-type gastric adenocarcinoma because of their different biological behavior. We immunohistochemically analyzed hepatocellular markers (AFP, glypican 3, and Hepatocyte paraffin 1 [HepPar-1]) and possible markers of gastric hepatoid adenocarcinoma (Sal-like protein 4 [SALL4] and palate, lung, and nasal epithelium carcinoma-associated protein [PLUNC]) to detect hepatoid differentiation in 45 gastric hepatoid adenocarcinomas and 47 nonhepatoid solid-type poorly differentiated adenocarcinomas. There were a higher incidence of vascular invasion (P = .0055) and distant metastasis (P = .0458) in hepatoid adenocarcinoma than in nonhepatoid adenocarcinoma. AFP, SALL4, HepPar-1, and glypican 3 were significantly higher in hepatoid adenocarcinoma than in nonhepatoid adenocarcinoma. All 5 markers were positive in both the hepatoid/solid and the tubular component. In hepatoid adenocarcinoma, the frequency of distant metastasis was significantly higher in SALL4-negative cases than in SALL4-positive cases (P = .0381). HepPar-1 was associated with liver metastasis (P = .0452). PLUNC was correlated with lymph node metastasis (P = .0375). There was a significant difference in the survival rate between HepPar-1-positive and HepPar-1-negative groups (P = .0437). The coexpression of PLUNC and SALL4 and the other coexpression of HepPar-1 and PLUNC were associated with poorer prognosis (P = .0181 and P = .0443, respectively). AFP, SALL4, HepPar-1, and glypican 3 are useful for the detection of hepatoid differentiation. A combination of PLUNC, HepPar-1, and SALL4 could be a reliable prognostic indicator in hepatoid adenocarcinoma of the stomach.

Aberrant activation-induced cytidine deaminase expression is associated with mucosal intestinalization in the early stage of gastric cancer.

Although Helicobacter pylori is a risk factor for gastric cancer (GC), its detailed carcinogenesis remains unclear. Recently, aberrant expression of activation-induced cytidine deaminase (AID) was demonstrated in gastric epithelium with H. pylori infection and seems to cause the accumulation of mutation. This investigation aims to elucidate whether or not AID expression plays an important role in the carcinogenesis of early GC. We examined the correlation between immunohistochemical AID expression and histological characteristics, including pre-existing chronic gastritis and cellular mucin phenotype in 138 cases of intramucosal GC. Furthermore, we investigated the relationship between AID, p53 protein, and ß-catenin. The low degree of polymorphonuclear neutrophil activity, and the high degree of glandular atrophy and intestinal metaplasia were significantly correlated with the high levels of AID expression in non-neoplastic mucosa (P = 0.007, P ≤ 0.001, and P = 0.003). With regard to mucin phenotype of carcinoma, the intestinal phenotype tended to have the higher AID expression levels (P = 0.052). AID showed close correlations with Cdx2 and nuclear staining of ß-catenin (P = 0.003, P = 0.034). As for p53 protein, no correlation was found with AID expression. Our findings suggest that aberrant AID expression is correlated with persistent inflammatory condition induced by H. pylori infection and may contribute to the development of GC through an inflammatory condition and intestinalization.