Background/Purpose
Recurrence of ampullary neoplasms after endoscopic papillectomy (EP) has not been well elucidated. This study aimed to clarify the predictive factors for recurrences after EP. We ...also aimed to investigate the retreatment of the recurrent lesions and their outcomes.
Methods
This multicenter, retrospective cohort study included 96 patients with ampullary neoplasms who underwent EP at four tertiary centers between January 2000 and October 2018.
Results
The pathological diagnoses of resected specimens confirmed adenoma in 62 and adenocarcinoma in 34 patients (six Tis, 24 T1a, three T1b, one inconclusive). Complete resection was confirmed for 79 patients (82.3%). Recurrent lesions were observed in 13 patients (13.5%) during a median follow‐up of 3 months (1‐36 months) after EP. The predictive factors of recurrence were piecemeal resection, and non‐negative horizontal or vertical margin in univariate analysis. Non‐negative vertical margin was the only independent predictive factor of recurrence in the multivariate analysis. The recurrent lesions were treated endoscopically in 11 patients. Recurrence after the endoscopic retreatments was observed in one patient.
Conclusions
Complete resection with negative vertical margin is an important factor in preventing the recurrence of ampullary neoplasms after EP. Endoscopic retreatments are also feasible for recurrent lesions.
Highlight
Takahashi and colleagues analyzed endoscopic papillectomy data from 96 patients. The complete resection and recurrence rates were 82.3% and 13.5%, respectively. A non‐negative vertical margin was an independent predictive factor of recurrence. Complete resection and a negative vertical margin are important factors in preventing the recurrence of ampullary neoplasms after endoscopic papillectomy.
A 54-year-old man was admitted to our hospital for examination and treatment of a duodenal elevated lesion. Esophagogastroduodenoscopy revealed a submucosal tumor with a diameter of about 20mm ...located at the duodenal main papilla. Endoscopic ultrasonography showed a 20×17 mm, hypoechoic tumor that was located in the submucosa without any sign of invasion to adjacent structures. We observed no lymph node nor distant metastases in any images. Accordingly, we performed endoscopic snare papillectomy in this patient. After excision, pathological examination revealed that this tumor was a gangliocytic paraganglioma (GP) and that we had removed the tumor completely. Because of its benign nature, we should remove GP by a less invasive therapy such as endoscopic papillectomy for complete biopsy. To our knowledge, reports on GP excised endoscopically are rare; therefore, we report this case.
SHPS-1 is a receptor-type glycoprotein that binds and activates the protein-tyrosine phosphatases SHP-1 and SHP-2, and thereby
negatively modulates intracellular signaling initiated by various cell ...surface receptors coupled to tyrosine kinases. SHPS-1
also regulates intercellular communication in the neural and immune systems through its association with CD47 (integrin-associated
protein) on adjacent cells. Furthermore, recent studies with fibroblasts derived from mice expressing an SHPS-1 mutant that
lacks most of the cytoplasmic region suggested that the intact protein contributes to cytoskeletal function. Mice homozygous
for this SHPS-1 mutation have now been shown to manifest thrombocytopenia. These animals did not exhibit a defect in megakaryocytopoiesis
or in platelet production. However, platelets were cleared from the bloodstream more rapidly in the mutant mice than in wild-type
animals. Furthermore, peritoneal macrophages from the mutant mice phagocytosed red blood cells more effectively than did those
from wild-type mice; in addition, they exhibited an increase both in the rate of cell spreading and in the formation of filopodia-like
structures at the cell periphery. These results indicate that SHPS-1 both contributes to the survival of circulating platelets
and down-regulates the macrophage phagocytic response.
SHPS-1 is a receptor-like protein that undergoes tyrosine phosphorylation and binds SHP-2, an SH2 domain-containing protein tyrosine phosphatase, in response to insulin and other mitogens. The ...overexpression of wild-type SHPS-1, but not of a mutant SHPS-1 in which all four tyrosine residues in its cytoplasmic region were mutated to phenylalanine, markedly enhanced insulin-induced activation of mitogen-activated protein kinase in Chinese hamster ovary cells that overexpress the human insulin receptor. Mutation of each tyrosine residue individually revealed that the major sites of tyrosine phosphorylation of SHPS-1 in response to insulin are Tyr449 and Tyr473. In addition, mutation of either Tyr449 or Tyr473 abolished the insulin-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Surface plasmon resonance analysis showed that glutathioneS-transferase fusion proteins containing the NH2-terminal or COOH-terminal SH2 domains of SHP-2 bound preferentially to phosphotyrosyl peptides corresponding to the sequences surrounding Tyr449 or Tyr473, respectively, of SHPS-1. Furthermore, phosphotyrosyl peptides containing Tyr449 or Tyr473 were effective substrates for the phosphatase activity of recombinant SHP-2 in vitro. Together, these results suggest that insulin may induce phosphorylation of SHPS-1 at Tyr449 and Tyr473, to which SHP-2 then binds through its NH2-terminal and COOH-terminal SH2 domains, respectively. SHPS-1 may play a crucial role both in the recruitment of SHP-2 from the cytosol to a site near the plasma membrane and in increasing its catalytic activity, thereby positively regulating the RAS-mitogen-activated protein kinase signaling cascade in response to insulin.
Stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1), a transmembrane-type protein-tyrosine phosphatase, is thought to inhibit integrin signaling by mediating the dephosphorylation of ...focal adhesion-associated proteins. Adenovirus-mediated overexpression of wild-type SAP-1, but not that of a catalytically inactive mutant of this enzyme, has now been shown to induce apoptosis in NIH 3T3 fibroblasts. This effect of SAP-1 was dependent on cellular caspase activities and was preceded by inactivation of two serine-threonine protein kinases, Akt and integrin-linked kinase (ILK), both of which function downstream of phosphoinositide (PI) 3-kinase to promote cell survival. Coexpression of constitutively active forms of PI 3-kinase or Akt (which fully restored Akt and ILK activities) resulted in partial inhibition of SAP-1-induced cell death. Furthermore, expression of a dominant negative mutant of PI 3-kinase did not induce cell death as efficiently as did SAP-1, although this mutant inhibited Akt and ILK activities more effectively than did SAP-1. Overexpression of SAP-1 had no substantial effect on Ras activity. These results suggest that SAP-1 induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway.