Barrett's esophagus is considered a precancerous lesion of esophageal adenocarcinoma (EAC). Long‐segment Barrett's esophagus, which is generally associated with intestinal metaplasia, has a higher ...rate of carcinogenesis than short‐segment Barrett's esophagus, which is mainly composed of cardiac‐type mucosa. However, a large number of cases reportedly develop EAC from the cardiac‐type mucosa which has the potential to involve intestinal phenotypes. There is no consensus regarding whether the definition of Barrett's epithelium should include intestinal metaplasia. Basic researches using rodent models have provided information regarding the origins of Barrett's epithelium. Nevertheless, it remains unclear whether differentiated gastric columnar epithelium or stratified esophageal squamous epithelium undergo transdifferentiation into the intestinal‐type columnar epithelium, transcommittment into the columnar epithelium, or whether the other pathways exist. Reflux of duodenal fluid including bile acids into the stomach may occur when an individual lies down after eating, which could cause the digestive juices to collect in the fornix of the stomach. N‐nitroso‐bile acids are produced with nitrites that are secreted from the salivary glands, and bile acids can drive expression of pro‐inflammatory cytokines via EGFR or the NF‐κB pathway. These steps may contribute significantly to carcinogenesis.
Background
We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model).
Aims
We aimed to investigate ...the characteristics and histogenesis of PACM using a reflux model.
Methods
A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach–jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2.
Results
In all reflux model rats, PACM was observed proximal to the glandular stomach–jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083.
Conclusions
PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration.
Background
Rat gastroduodenal reflux models have been used for analyzing Barrett’s carcinogenesis. Mice seem to be more useful than rats for studies targeting genes.
Methods
We induced gastroduodenal ...contents reflux by esophagojejunostomy using C57BL/6J mice. Mice were divided into a standard diet and high-fat diet groups and kept for 60 weeks. Bile was sampled from the gallbladder to analyze bile acid fractions, and the esophagus was removed for a histological investigation. Human esophagogastric junction adenocarcinoma cells (OE19) were exposed to taurocholic acid (TCA), after which cell proliferative activity was measured. Rat esophageal cancer cell lines, ESCC-DR and ESCC-DRtca with higher malignant potential induced by continuous TCA exposure, were used to perform comprehensive genetic analysis (CGH).
Results
Barrett’s epithelium onset occurred in all mice, and no differences in histological changes were noted between the standard diet and high-fat diet groups. However, no development of adenocarcinoma was noted. Most of the mouse bile acid was taurine conjugates. In the experiment using OE-19 cells, TCA promotes cell proliferation in a dose-dependent manner. Array CGH analysis revealed a large number of chromosomal abnormalities in the ESCC-DR, in addition to genetic abnormalities such as in the UGT2B gene, the substrate of which is bile acid. TCA administration resulted in more chromosomal abnormalities being detected.
Conclusions
We showed the effects of TCA in cancer progression in vitro. However, Barrett’s adenocarcinoma onset rates differ between mice and rats despite undergoing similar reflux stimulation including taurine-conjugated bile acids being detected in mouse bile juice. These results suggest that host factors seem to influence Barrett’s carcinogenesis.
Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was ...achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years.
A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression.
To the best of our knowledge, this is the longest treatment with regorafenib without tumor progression ever reported. A reduced dosage of regorafenib at induction may ameliorate the cutaneous and hepatic toxicity associated with its use.
This case involved a 76-year-old woman found to have occult blood in her stool. The patient underwent further testing in the form of lower gastrointestinal tract endoscopy, which revealed type Ip ...polyps in the descending colon. These were diagnosed as hyperplastic polyps, so a polypectomy was performed, but poorly differentiated adenocarcinoma and mucinous carcinoma were found in most of the resection specimens. Margins were positive, so further resection of the bowel was performed. Preoperative image findings also suggested para-aortic lymph node metastasis, therefore para-aortic lymph node dissection was also performed. Residual tumor cells were not found in the resected intestine but para-aortic lymph node metastasis was present, so the final diagnosis was adenocarcinoma, por2, muc>tub2 type 0-Ip, pSM (>5,000 μm), int, INFb, ly0, v1, M1 Stage IV. Characteristic endoscopic findings in this case indicated that lesions had invaded deep into the submucosa and had resulted in distal lymph node metastasis. The cross-sectional morphology of these lesions and their relationship to histological findings are described here, along with a discussion of some of the literature.
Objective : To investigate the effects of obesity on perioperative outcomes in laparoscopic surgery for right-sided colon cancer. Subjects and methods : The subjects were 80 patients who underwent ...laparoscopic surgery for right-sided colon cancer between April 2010 and December 2013. They were classified into obese and non-obese groups using a body mass index (BMI) of ≥25 kg/m2 and a visceral fat area (VFA) on X-ray computed tomography (CT) of ≥100 cm2 as reference values. Patient background characteristics and perioperative outcomes were investigated retrospectively. Results : No significant intergroup differences were found for patient background characteristics or postoperative outcomes. As for surgical outcomes, operative time was significantly longer (P=0.026) and intraoperative blood loss was significantly higher (P=0.025) in the high VFA group, but no significant intergroup differences were observed by BMI classification. Conclusion : In laparoscopic surgery for right-sided colon cancer, VFA, which reflects the amount of visceral fat, was considered a better obesity-related indicator than BMI for accurately predicting the level of surgical difficulty.
A 73-year-old man who consulted our hospital with a chief complaint of upper abdominal pain was admitted with a diagnosis of acute pancreatitis. An image of a localized irregular narrow segment was ...observed in the main pancreatic duct of the pancreatic head upon ERCP, with a poorly contrasting region measuring 8 mm in size, corresponding to the narrow segment observed on abdominal CT. A blocked main pancreatic duct and common bile duct were observed in the vicinity of the pancreaticobiliary duct upon MRCP. Based on the laboratory finding, pancreaticoduodenectomy and right nephrectomy were performed with a preoperative diagnosis of pancreatic cancer and right renal cell cancer. As no malignant findings were observed in the resected specimen, and only plant tissue was found in the main pancreatic duct in histopathological laboratory findings, it was diagnosed as obstructive pancreatitis caused by a foreign substance in the main pancreatic duct. The mechanism of the appearance of the foreign substance in the main pancreatic duct was unknown in this case because the patient had no history of drug use that was likely to influence the function of the papillary sphincter muscle or a history of choledocholithiasis, and because no evident morphological defects in the duodenal papilla were found through imaging.
A 74-year-old male with epigastric pain was found to have an increased inflammatory response and elevated serum and urine amylase levels. The patient was diagnosed as having acute pancreatitis. ...Abdominal CT scan revealed dilation of the main pancreatic duct and lower portion of the bile duct, as well as a hypodensity in the tail of the pancreas. The patient developed peritoneal signs, and another abdominal CT scan was performed. The patient was diagnosed as having peritonitis due to a perforated gallbladder ; percutaneous transhepatic gall bladder drainage and abdominal drainage were required. Preoperatively, the patient was diagnosed as having an intraductal papillary mucinous neoplasm. Once the patient was stabilized, a cholecystectomy, a distal pancreatectomy, and a splenectomy were performed. The pancreatic tumor was on pathology diagnosed as an intraductal papillary-mucinous adenoma mixed type, 24 mm×21 mm in size. There are no reports of patients with an intraductal papillary mucinous neoplasm developing a perforated gallbladder. In the current patient, there was an increase in the pressure in the pancreaticobiliary ducts caused by mucus produced by the tumor, as well as cholestasis and pancreatobiliary reflux ; this could have led to the perforation.
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