[A Case of Gastric Submucosal Tumor at Esophagogastric Junction Resected by Endoscopic Intragastric Surgery].

We report a case in which a gastric submucosal tumor at the esophagogastric junction was resected by endoscopic intragastric surgery with minimally invasive and function-preserving. A 30s-year-old man was referred to our hospital because of an abnormal findings pointed by a barium examination at a health check up. Upper gastrointestinal endoscopy and endoscopic ultrasound revealed a submucosal tumor approximately 60 mm in size on the posterior wall of the gastric fundus. Endoscopic ultrasound-fine needle aspiration was carried out and pathological result was a leiomyoma. The tumor was an intraluminal and extraluminal growth extending from the dorsal esophagus to the cardiac region, but considering the patient's young age, we decided to perform endoscopic intragastric surgery to preserve the function of stomach. A 30 mm median incision was made above the umbilicus, and the anterior wall of the gastric body was incised and the intragastric surgery was started using the double protector method. The mucosal surface of the tumor was located at the fundus, but the tumor developed into the dorsal aspect of the lower esophageal muscle layer. The tumor was carefully dissected and resected by intragastric manipulation. Postoperative oral contrast examination revealed no obvious stenosis, and gastric peristalsis was normal.

The malignant potential of pancreatic intraductal papillary mucinous neoplasm is reflected in expression levels of fucosylated glycans in α1 -acid glycoprotein.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasm (IPMN) involves multiple histopathological stages from benign to malignant lesions. Further, a biomarker to diagnose the malignant IPMN (IPMC) is clinically relevant. Recently, we found that serum fucosylated α1 -acid glycoprotein (fAGP) level markedly elevated along with disease progression in large cohorts of patients with various cancers. METHODS: The fAGP level was retrospectively analyzed in preoperative sera from 109 patients with IPMN, and the clinical relevance of fAGP was compared with currently available predictors as standard. RESULTS: The fAGP level in IPMC was found to be significantly higher than in benign IPMN (P = .0012). At a cutoff value of 27.04 U/µg, its sensitivity, specificity, and accuracy for IPMC were determined to be 83.61%, 65.96%, and 75.93%, respectively. Multivariate analyses revealed that the fAGP level was the only independent risk factor for predicting IPMC. Additionally, a combination of the fAGP level and 18 F-fluorodeoxyglucose uptake on the PET/CT imaging in the lesions seemed to offer the best diagnosis of IPMN. Accordingly, 27 of the 28 patients who were positive in both tests had IPMC, while patients who are negative had benign IPMN. CONCLUSIONS: The fAGP level appeared to be a relevant biomarker for malignant potential of IPMN.

N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma.

In pancreatic cancer, methyltransferase-like 3 (METTL3), a N(6)-methyladenosine (m6A) methyltransferase, has a favorable effect on tumors and is a risk factor for patients' prognosis. However, the details of what genes are regulated by METTL3 remain unknown. Several RNAs are methylated, and what genes are favored in pancreatic cancer remains unclear. By epitranscriptomic analysis, we report that polo-like kinase 1 (PLK1) is an important hub gene defining patient prognosis in pancreatic cancer and that RNA methylation is involved in regulating its cell cycle-specific expression. We found that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) binds to m6A of PLK1 3' untranslated region and is involved in upregulating PLK1 expression and that demethylation of this site activates the ataxia telangiectasia and Rad3-related protein pathway by replicating stress and increasing mitotic catastrophe, resulting in increased radiosensitivity. This suggests that PLK1 methylation is essential for cell cycle maintenance in pancreatic cancer and is a new therapeutic target.

Inhibition of Clusterin Represses Proliferation by Inducing Cellular Senescence in Pancreatic Cancer.

BACKGROUND: The outcome of pancreatic ductal adenocarcinoma (PDAC) is unsatisfactory, and the identification of novel therapeutic targets is urgently needed. Clinical studies on the antisense oligonucleotide that targets clusterin (CLU) expression have been conducted and have shown efficacy in other cancers. We aimed to investigate the effects of CLU in PDAC and the underlying mechanisms with a view to the clinical application of existing drugs. METHODS: We knocked down CLU in PDAC cells and evaluated changes in cell proliferation. To elucidate the mechanism responsible for these changes, we performed western blot analysis, cell cycle assay, and senescence-associated ß-galactosidase (SA-ß-gal) staining. To evaluate the clinical significance of CLU, immunohistochemistry was performed, and CLU expression was analyzed in specimens resected from PDAC patients not treated with preoperative chemotherapy. RESULTS: Knockdown of CLU significantly decreased cell proliferation and did not induce apoptosis, but did induce cellular senescence by increasing the percentage of G1-phase and SA-ß-gal staining-positive cells. A marker of DNA damage such as γH2AX and factors related to cellular senescence, such as p21 and the senescence-associated secretory phenotype, were upregulated by knockdown of CLU. CLU expression in resected PDAC specimens was located in the cytoplasm of tumor cells and revealed significantly better recurrence-free survival and overall survival in the CLU-low group than in the CLU-high group. CONCLUSIONS: We identified that CLU inhibition leads to cellular senescence in PDAC. Our findings suggest that CLU is a novel therapeutic target that contributes to the prognosis of PDAC by inducing cellular senescence.

ACAT-1-Regulated Cholesteryl Ester Accumulation Modulates Gemcitabine Resistance in Biliary Tract Cancer.

BACKGROUND: Biliary tract cancer (BTC) has few choices of chemotherapy, including gemcitabine, therefore exploring the mechanisms of gemcitabine resistance is important. We focused on lipid metabolism because biliary tract epithelial cells are essential in cholesterol and bile acid metabolism and the messenger RNA (mRNA) microarray analysis showed high acyl coenzyme A: cholesterol acyltransferase 1 (ACAT-1) expression in BTC gemcitabine-resistant (GR) cell lines. We hypothesized that aberrant accumulation of cholesteryl ester (CE) regulated by ACAT-1 could modulate GR in BTC. METHODS: CE accumulations were measured in human BTC cell lines, and the relationships between CE levels, ACAT-1 expressions, and gemcitabine sensitivity were analyzed. We performed a small-interfering RNA (siRNA)-mediated knockdown and biochemical inhibition of ACAT-1 in BTC cell lines and alterations of gemcitabine sensitivity were evaluated. To evaluate the clinical significance of ACAT-1 in regard to GR, immunohistochemistry was performed and ACAT-1 expressions were analyzed in resected BTC specimens. RESULTS: CE levels were correlated with ACAT-1 expressions and GR in four human BTC cell lines. siRNA-mediated knockdown of ACAT-1 in two independent GR cell clones as well as ACAT-1 inhibitor treatment significantly increased gemcitabine sensitivity; knockdown of ACAT-1: 5.63- and 8.02-fold; ACAT-1 inhibitor: 8.75- and 9.13-fold, respectively. ACAT-1 expression in resected BTC specimens revealed that the disease-free survival of the ACAT-1 low-intensity group (median 2.3 years) had a significantly better outcome than that of the ACAT-1 high-intensity group (median 1.1 years) under gemcitabine treatment after surgery (*p < 0.05). CONCLUSIONS: Our findings suggest that CE and ACAT-1 might be a novel therapeutic target for GR in BTC.

Enterococcus spp. have higher fitness for survival, in a pH-dependent manner, in pancreatic juice among duodenal bacterial flora.

BACKGROUND AND AIM: Bacterial infection is involved in the progression of many gastrointestinal diseases, including those of pancreas; however, how and which bacteria colonize in pancreatic juice and tissue have yet to be elucidated. Recently, we reported that Enterococcus faecalis exists in the pancreatic juice and tissues of patients with chronic pancreatic disease. Here, we investigated the survival of E. faecalis in duodenal juice with different pH conditions. METHODS: Pancreatic juice samples from 62 patients with cancers of the duodeno-pancreato-biliary region were evaluated for the presence of E. faecalis. 16S ribosomal RNA polymerase chain reaction and 16S-based metagenome analyses were performed to determine the bacterial composition. The survival of E. faecalis in various pancreatic juice conditions was evaluated. RESULTS: Of 62 samples, 27% (17/62) were positive for Enterococcus spp., among which 71% (12/17) contained E. faecalis. Enterococcus spp. showed the highest fitness for survival in alkaline pancreatic juice among various bacterial species. The microbiome of pancreatic juice from patients with pancreatic and bile duct cancer showed diversity, but Enterococcus spp. were enriched among duodenal tumors and intraductal papillary mucinous neoplasms. CONCLUSIONS: Alkalinity is one of the important factors for the selective survival of E. faecalis among microbiota. E. faecalis can colonize the pancreatic duct when the pancreatic juice condition is altered.

[A Case of Giant Mesenteric Lymphangioma in an Adult].

A 26-year-old man with left inguinal pain and frequent urination was examined. An abdominal ultrasound revealed a cystic lesion. In further examinations, CT and MRI showed a large cystic lesion of about 20 cm in size, connected to mesenteric- derived blood vessels. We suspected a huge mesenteric lymphangioma and decided to perform a laparotomy. A tumor was seen in the mesentery of the jejunum and adhered to the duodenum widely. The tumor could be removed safely without resection of the duodenum by first sucking the contents and shrinking the tumor. The final pathological diagnosis was mesenteric lymphangioma. Adult mesenteric lymphangiomas measuring larger than 20 cm are relatively rare. We review the case in the context of the relevant literature.

[A Case of Gastric Anisakiasis That Required Differentiation from Scirrhous Gastric Cancer].

A 36-year-old woman visited a previous doctor with lower abdominal pain and nausea. Her former doctor's upper gastrointestinal endoscopy and CT scan showed giant folds and wall thickening of the lower body of the stomach, and she was referred on suspicion of scirrhous gastric cancer. Similar findings were found on enhanced CT at our hospital. Endoscopic findings performed several days later showed red and thickened mucosa at the cardia, but no wall thickening and giant fold, and there were no findings suggestive of scirrhous gastric cancer. Biopsy showed no atypical cells, and a large number of eosinophils appeared in the lesion at the cardia. Eosinophilia and anisakis IgE antibody were positive and a diagnosis of gastric anisakiasis was made. She was eating grilled horse mackerel the day before her stomachache. At the same time, pruritus and edema around her right knee also appeared, and a dermatologist diagnosed her with anisakis-related eosinophil edema. One month later, CT scan and endoscopy were almost normal. A young woman referred on suspicion of scirrhous gastric cancer experienced a rare case diagnosed with gastric anisakiasis.

[Radical Resection Was Achieved Using a Liver-First Approach for Simultaneous Liver Metastasis from Rectal Cancer-A Case Report].

The patient was a 70s male. A fecal occult blood test showed a positive reaction, and colonoscopy was performed. Under a diagnosis of rectal cancer, he was referred to our hospital. Detailed examination revealed solitary liver metastasis measuring 60 mm and involving the S4 to S1 areas of the liver. A strategy to perform systemic chemotherapy in advance was adopted. Five courses of FOLFOXIRI therapy were conducted, and a partial response(PR)was achieved, suggesting that the tumor is resectable. Extended left/caudal lobectomy was performed. There was no complication, and the patient was discharged. After 4 months, laparoscopic low anterior resection and temporary ileostomy were conducted. According to the TNM staging, the grade was evaluated as ypT2N0. On histological response evaluation, the grade was evaluated as 1a. The stoma was closed. During the 1.5-year follow-up after initial treatment, there has been no relapse. We encountered a patient with simultaneous liver metastasis from rectal cancer in whom the use of a liver-first approach(LFA)after systemic chemotherapy facilitated radical resection. The present case suggested that the LFA contributes to a rise in the resection rate, further improving the prognosis.

[Radiofrequency Ablation for Colorectal Liver Metastases].

AIM: The significance of radiofrequency ablation(RFA)for colorectal liver metastases(CRLM)remains to be elucidated. Therefore, this retrospective study aimed to evaluate the therapeutic efficacy of RFA for local recurrence of CRLM. SUBJECTS: Between June 2005 and June 2017, we retrospectively examined 63 patients(137 nodules)with CRLM who underwent RFA. RESULTS: The local recurrence rate was 36.5%, and the median local recurrence free survival(LRFS)was 26.3 months. We compared treatment background between the 2 groups with(50 nodules)and without(87 nodules)local recurrence. In the multivariate analysis, tumor size of the ablated lesion and method for ablation(direct tumor puncture)were independent risk factors for local recurrence. Receiver operating characteristic curve for tumor size of the ablated lesion showed an optimal cutoff value for tumor size of 1.8 cm(AUC=0.734, 95%CI: 0.612-0.855, p<0.0001). CONCLUSIONS: RFA for effective control of local recurrence of CRLM might be suitable for selected patients with tumor size of ablated lesion ofC1.8 cm and no touch ablation method.