Predictive factor of recurrence after endoscopic papillectomy for ampullary neoplasms.

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.

Efficacy of long-term 4.0 g/day mesalazine (Pentasa) for maintenance therapy in ulcerative colitis.

BACKGROUND: High-dose (4.0 g/day) mesalazine is typically used for induction therapy, but its efficacy as maintenance therapy remains to be determined. We conducted a multicenter retrospective study to investigate the efficacy of continuous treatment with 4.0 g/day of mesalazine. MATERIAL/METHODS: Japanese ulcerative colitis (UC) patients receiving acute induction therapy with 4.0 g/day mesalazine were enrolled and followed. Those who clinically improved or who achieved clinical remission were categorized into 2 sub-groups according to the median duration of treatment with 4.0 g/day of mesalazine. The clinical relapse frequency and the time to relapse were analyzed. RESULTS: We enrolled 180 patients with active UC, and then 115 patients who clinically improved or who achieved clinical remission after treatment with 4.0 g/day mesalazine were categorized into 2 sub-groups according to the median of treatment duration: a short-term treatment group (≤105 days, n=58) and a long-term treatment group (>105 days, n=57). Overall, 45 (39.1%) patients relapsed: 28 (48.3%) in the short-term treatment group and 17 (29.8%) in the long-term treatment group. This difference was statistically significant (p<0.05). The relapse-free rate in the long-term treatment group was significantly higher than that in the short-term treatment group (p<0.05). The mean time to relapse in the long-term treatment group was significantly longer than that in the short-term treatment group (425.6±243.8 days vs. 277.4±224.5 days; p<0.05). CONCLUSIONS: Long-term continuous treatment with high-dose mesalazine (4.0 g/day) may be more effective than short-term treatment for maintenance of remission in UC patients.

Endoscopic snare papillectomy with biliary and pancreatic stent placement for tumors of the major duodenal papilla.

BACKGROUND: This study aimed to evaluate the feasibility, safety, and follow-up results of endoscopic papilletomy (ESP) with pancreatic and biliary duct stent placement for ampullary tumors. The therapeutic approach to benign ampullary tumors remains unsettled. The ESP procedure is a curative treatment option for benign papillary tumors, but ESP raises concerns about a relatively high risk for procedure-related complications such as pancreatitis. A pancreatic stent may protect against complications. METHODS: Between September 2000 and June 2008, 36 patients with ampullary tumors confined to the mucosa and no intraductal tumor growth underwent ESP. The preprocedural diagnostic tools included endoscopic ultrasound, transpapillary intraductal ultrasound, and endoscopic retrograde cholangiopancreatography. Pancreatic and biliary stent placement was attempted if feasible. Endoscopic follow-up evaluation was conducted periodically as surveillance for recurrence. RESULTS: En bloc ESP was achieved for 94% of lesions with a median size of 14 mm. There were 26 adenomas including 4 high-grade intraepithelial neoplasias (HGINs), 5 carcinomas in adenoma, and 3 intramucosal cancers. Complete resections with tumor-free lateral and basal margins was achieved for 81% of the cases. During the median follow-up period of 14 months, there was one recurrent adenoma, which was successfully eradicated by a repeat ESP. A pancreatic stent was placed in 35 cases and a biliary stent in 29 cases. Mild acute pancreatitis and bleeding, managed endoscopically, occurred in 3 cases each (8%). CONCLUSION: The ESP procedure can be feasible for benign ampullary adenoma, HGIN, and noninvasive cancer without intraductal tumor growth. Prophylactic stent placement in the pancreatic and bile ducts may reduce procedure-related complications.

Autoimmune pancreatitis with extreme elevation of DUPAN-2.

An 80-year-old woman was admitted to our hospital with complaints of jaundice and liver dysfunction. She was found to have a high titer of serum IgG4, positive rheumatoid factor and marked elevation of DUPAN-2 (11,148 U/ml). Computed tomography showed swelling of the pancreas, and endoscopic retrograde cholangiopancreatography revealed diffuse irregular narrowing of the main pancreatic duct, which are typical findings of autoimmune pancreatitis. There was no evidence of malignancy. Administration of 30 mg/day of prednisolone was started. Computed tomography showed significant regression in the size of the pancreas, and the stenosis of the main pancreatic duct was improved on ERCP. The serum level of DUPAN-2 was also markedly decreased after the treatment.

Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1.

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.

Induction of apoptosis by stomach cancer-associated protein-tyrosine phosphatase-1.

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.