HDAC Inhibitors as Epigenetic Regulators

Extent of the pancreatectomy was arguable while the result of SASI test was not well informative, to remove possible functional PNET and possible future malignant lesions, total pancreatectomy was performed. corticosteroid injection, coupled with pancreatoduodenectomy were performed to improve the individuals symptoms and to treat pancreatic tumors. The histology of multiple tumors in the duodenum and pancreas were all consistent with neuroendocrine tumors. His hypergastrinemia subsided and he remained asymptomatic in his gastrointestinal tract after these treatments. Summary For esophageal stenosis in case of MEN1/ZES, anti-secretory therapy and endoscopic dilatation with corticosteroid injection could be recommended. However, in refractory instances with repeated and/or severe complications due to high acid secretion, surgical treatment could be considered as an option. gene is acknowledged in 80C90% of familial cases and in about 65% of sporadic cases [1]. They are sometimes associated with gastrinomas [Zollinger-Ellison syndrome (ZES)] [1], which induce gastric hypersecretion and cause not only gastroduodenal ulcers but also reflux esophagitis [2], in combination with hypercalcemia due to hyperparathyroidism. Heartburn is usually a typical symptom of reflux esophagitis and is acknowledged in about 50% of cases of MEN1. Anti-acid therapies, such as proton pump inhibitors (PPI) and H2 receptor antagonists, are effective [2]. MEN1 with ZES also develops dysphagia due to esophageal strictures in a small proportion (9%) [2], and their endoscopic treatment has rarely been reported. This report presents a case of MEN1 with ZES that developed esophageal strictures which were successfully treated with repetitive procedures of endoscopic dilation with local steroid injection combined with duodenectomy and total pancreatectomy. Case presentation A 43-year-old man frequented the nearest hospital for examination of his increasing complaints of nausea and diarrhea for 4?years and recent development of dysphagia. He had a history of duodenal ulcer perforation, and underwent omental patching surgery 4?years earlier, followed by oral treatment with a PPI (30?mg/day of lansoprazole). Octreotide analog was not used. Upper gastrointestinal endoscopy (UGE) exhibited reflux erosive esophagitis with severe esophageal stricture. Plain computed tomography (CT) showed a urinary tract stone and a pancreatic mass. Despite continuous anti-acid therapy, perforation of the small intestine developed, and he underwent closure surgery. Using the selective arterial secretagogue injection (SASI) test, a response by calcium injection was obtained when examined from the superior mesenteric artery, which connects to the feeding arteries to either the pancreatic head, body, or tail. However, it was not obtained by the examinations from the gastroduodenal artery and splenic artery. The patient was referred to the study hospital to further investigate the suspected diagnosis of MEN1. Blood examination revealed an elevated level of serum gastrin (3000?pg/mL, normal: 200?pg/mL), glucagon (253?pg/mL, normal: 70C174?pg/mL), calcium (10.9?mg/dL, normal: 8.5C10.2?mg/dL) and intact-parathyroid hormone (PTH) (104?pg/mL, normal: PTPRQ 10C65?pg/mL). Enhanced CT exhibited multiple highly vascular lesions within the pancreas (head to tail) and duodenum, with up to 20?mm in the pancreas (Fig.?1). UGE exhibited healing of the esophageal erosion, however the stenosis at the lower esophagus, approximately 4?mm in diameter and 5?cm in length, became so severe that only a slim endoscope (Olympus GIF-XP260, Tokyo, Japan), but not a standard scope (Olympus GIF-H260), could pass through. Multiple gastroduodenal ulcer scars were observed. In the second portion of the duodenum, a submucosal tumor, 12?mm in size, was also recognized (Fig.?2). Open in a separate window Fig. 1 Enhanced computed tomography showing multiple highly vascular tumors within the pancreas and the duodenum; a well demarcated duodenal tumor protruding into the lumen (a), a tumor at the head (b), body (c), and tail (d) of the pancreas Open in a separate windows Fig. 2 Endoscopic view of the esophageal stenotic portion (a), dilation with a balloon catheter (b), corticosteroid injection by a needle (c), at the last observation (d), and the duodenal submucosal tumor (e) Considering these findings associated with hypergastrinemia, it was planned to treat the esophageal stricture and neuroendocrine tumors.Blood examination revealed an elevated level of serum gastrin (3000?pg/mL, normal: 200?pg/mL), glucagon (253?pg/mL, normal: 70C174?pg/mL), calcium (10.9?mg/dL, normal: 8.5C10.2?mg/dL) and intact-parathyroid hormone (PTH) (104?pg/mL, normal: 10C65?pg/mL). and he remained asymptomatic in his gastrointestinal tract after these treatments. Conclusion For esophageal stenosis in case of MEN1/ZES, anti-secretory therapy and endoscopic dilatation with corticosteroid injection could be recommended. However, in refractory cases with repetitive and/or severe complications due to high acid secretion, surgical treatment could be considered as an option. gene is acknowledged in 80C90% of familial cases and in about 65% of sporadic cases [1]. They are sometimes associated with gastrinomas [Zollinger-Ellison syndrome (ZES)] [1], which induce gastric hypersecretion and cause not only gastroduodenal ulcers but also reflux esophagitis [2], in combination with hypercalcemia due to hyperparathyroidism. Heartburn is usually a typical symptom of reflux esophagitis and is acknowledged in about 50% of cases of MEN1. Anti-acid therapies, such as proton pump inhibitors (PPI) and H2 receptor antagonists, are effective [2]. MEN1 with ZES also develops dysphagia due to esophageal strictures in a small proportion (9%) [2], and their endoscopic treatment has rarely been reported. This report presents a case of MEN1 with ZES that developed esophageal strictures which were successfully treated with repetitive procedures of endoscopic dilation with local steroid injection combined with duodenectomy and total pancreatectomy. Case presentation A 43-year-old man frequented the nearest hospital for examination of his increasing complaints of nausea and diarrhea for 4?years and recent development of dysphagia. He had a history of duodenal ulcer perforation, and underwent omental patching surgery 4?years earlier, followed by oral treatment with a PPI (30?mg/day of lansoprazole). Octreotide analog was not used. Upper gastrointestinal endoscopy (UGE) exhibited reflux erosive esophagitis with severe esophageal stricture. Plain computed tomography (CT) showed a urinary tract stone and a pancreatic mass. Despite continuous anti-acid therapy, perforation of the small intestine developed, and he underwent closure surgery. Using the selective arterial secretagogue injection (SASI) test, a response by calcium injection was obtained when examined from the superior mesenteric artery, which connects to the feeding arteries to either the pancreatic head, body, or tail. However, it was not obtained by the examinations from the gastroduodenal artery and splenic artery. The patient was referred to the study hospital to further investigate the suspected diagnosis of MEN1. Blood examination revealed an elevated level of serum gastrin (3000?pg/mL, normal: 200?pg/mL), glucagon (253?pg/mL, normal: 70C174?pg/mL), calcium (10.9?mg/dL, normal: 8.5C10.2?mg/dL) and intact-parathyroid hormone (PTH) (104?pg/mL, normal: 10C65?pg/mL). Enhanced CT exhibited multiple highly vascular lesions within Kartogenin the pancreas (head to tail) and duodenum, with up to 20?mm in the pancreas (Fig.?1). UGE exhibited healing of the esophageal erosion, however the stenosis at the lower esophagus, approximately 4?mm in diameter and 5?cm in length, became so severe that only a slim endoscope (Olympus GIF-XP260, Tokyo, Japan), but not a standard scope (Olympus GIF-H260), could pass through. Multiple gastroduodenal ulcer scars were observed. In the second portion of the duodenum, a submucosal tumor, 12?mm in size, was also recognized (Fig.?2). Open in a separate windows Fig. 1 Enhanced computed tomography showing multiple highly vascular tumors within the pancreas and the duodenum; a well demarcated duodenal tumor protruding into the lumen (a), a tumor at the head (b), body (c), and tail (d) of the pancreas Open in a separate windows Fig. 2 Endoscopic view of the esophageal stenotic portion (a), dilation with a balloon catheter (b), corticosteroid injection by a needle (c), at the last observation (d), and the Kartogenin duodenal submucosal tumor (e) Considering these findings associated with hypergastrinemia, it was planned to treat the esophageal stricture and neuroendocrine tumors prior to the treatment of the hyperparathyroidism. Balloon Kartogenin dilator treatment (CRETM, 15C18?mm, Boston Scientific, Marlborough, MA, U.S.A.) (Fig.?2) was repeated 16 occasions, before and after the total pancreatectomy with duodenectomy, until the disappearance of the esophageal stricture. The interval between each procedure was almost once a week for the first 10 procedures, except for the month of the surgical period, followed by two weeks for the 11th-12th procedures, and one to three months for the 13th-16th procedures. Balloon dilation was done for 30C60 s with pressure stepped up as in the following: limited up to 1 1.5C2?atm for the initial five methods, 3C4?atm for another five methods, and 4C5?atm for the rest of the procedures. Since complete dilation had not been Kartogenin obtained before 5th treatment, 50?mg (5?ml) of triamcinolone acetonide (Kenacort-A, Bristol-Myers Squibb, NY, U.S.A.) was injected towards the.