• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.1
• /
• pp.373-376
• /
• 2015

Background: EVA1A (eva-1 homolog A) is a novel gene that regulates programmed cell death through autophagy and apoptosis. Our objective was to investigate the expression profiles and potential role of EVA1A in normal and neoplastic human pancreatic tissues. Materials and Methods: The expression pattern of EVA1A in normal pancreatic tissue was examined by indirect immunofluorescence and confocal microscopy. Protein levels in paraffin-embedded specimens from normal and diseased pancreatic and matched non-tumor tissues were evaluated by immunohistochemistry. Results: EVA1A colocalized with glucagon but not with insulin, demonstrating production in islet alpha cells. Itwas strongly expressed in chronic pancreatitis, moderately or weakly expressed in the plasma membrane and cytoplasm in pancreatic acinar cell carcinoma, and absent in normal pancreatic acinar cells. Although the tissue architecture was deformed, EVA1A was absent in the alpha cells of pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, mucinous cystadenomas, solid papillary tumors and pancreatic neuroendocrine tumors. Conclusions: EVA1A protein is specifically expressed in islet alpha cells, suggesting it may play an important role in regulating alpha-cell function. The ectopic expression of EVA1A in pancreatic neoplasms may contribute to their pathogenesis and warrants further investigation.

• Annals of Hepato-Biliary-Pancreatic Surgery
• /
• v.27 no.2
• /
• pp.141-150
• /
• 2023

Pancreatic carcinosarcoma is a very rare malignancy with a poor prognosis. Because of these characteristics, a treatment strategy for it has not been established yet. The aim of this study was to establish a therapeutic strategy for pancreatic carcinosarcoma. We reviewed data of a 65-year-old female patient who was diagnosed with pancreatic carcinosarcoma through endoscopic ultrasound-guided fine needle aspiration biopsy before surgery. For literature review, we searched PubMed using terms of "Pancreatic" or "Pancreas" and "carcinosarcoma" or "carcinosarcomatous". The patient received 11 cycles of neoadjuvant treatment with leucovorin, fluorouracil, irinotecan, oxaliplatin and pembrolizumab because the tumor was borderline resectable. She underwent stereotactic ablative body radiotherapy (SABR) with 35 Gy in 5 fractions, followed by robotic pylorus-preserving pancreaticoduodenectomy. After surgery, the patient received adjuvant chemotherapy in the same regimen as before surgery. She is alive without any recurrence. Among 48 patients within 33 available papers, the median survival time was 15 months. The survival rate of patients who received adjuvant chemotherapy tended to be higher than that of those who did not receive adjuvant chemotherapy, although the difference was not statistically significant (median survival, 47 vs. 15 months; p = 0.485). Three patients who received neoadjuvant chemotherapy had a survival period of 13-23.5 months. Surgery with lymphadenectomy, adjuvant therapy, and neoadjuvant therapy are thought to help improve survival outcomes. Modern treatment approaches for conventional pancreatic ductal adenocarcinoma could be applied to pancreatic carcinosarcoma.

• Journal of Trauma and Injury
• /
• v.24 no.2
• /
• pp.111-117
• /
• 2011

Purposes: Pancreatic injury is rare in abdominal trauma patients (3%~12%). but it could result in significant morbidity and even mortality. Early and adequate decision making are very important in the management of patients with traumatic pancreatic injury. The purpose of this study was to assess the kinds of management and outcome through the review of our experience of pancreatic injury with multiple trauma. Methods: We reviewed 17 patients with traumatic pancreas injury via electronic medical records from Jan. 2002 and April. 2011. We collected demographic findings; the type, location and grade of pancreas injury, the treatment modality, and patient's outcomes, such as complications, length of hospital stay (LOS), and mortality. Results: Total 17 patients were reviewed, and man was 13 (88%). Traffic accident was the most common cause of injury. Pancreas neck was the most common injured site, and occured in 5 patients. Ductal injury was detected in 7 cases. Eleven patients were treated by surgical procedure, and in this group, 3 patients underwent the endoscopic retrograde pancreas drainage procedure coincidently. ERPD was tried in 8 patients, and failed in 2 patients. The major complications were post-traumatic fluid collection and abscess which accounted for 70 % of all patients. The hospital stay was 35.9 days, and it was longer in patient with ductal injury ($38.0{\pm}18.56$ vs. $34.5{\pm}33.68$ days). Only one patient was died due to septic shock associated with an uncontrolled retroperitoneal abscess. Conclusion: Early diagnosis is the most important factor to apply the adequate treatment option and to manage the traumatic pancreas injury. Aggressive treatment should be considered in patients with a post-operative abscess.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.7
• /
• pp.2719-2724
• /
• 2015

Objective: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Results: Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Conclusions: Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC.

• Journal of the Korean Society of Radiology
• /
• v.82 no.5
• /
• pp.1297-1303
• /
• 2021

Pancreatic collision tumors are rare neoplasm, and cases consisting of ductal adenocarcinoma with a neuroendocrine tumor, intraductal papillary mucinous neoplasm with a neuroendocrine tumor, and solid pseudopapillary neoplasm with a neuroendocrine tumor have been reported. We report a case of a rapidly growing pancreatic collision tumor consisting of desmoid-type fibromatosis and mucinous cystic neoplasm in a 30-year-old pregnant female. To the best of our knowledge, this is the first reported case of a pancreatic collision tumor consisting of desmoid-type fibromatosis and mucinous cystic neoplasm.

• Annals of Hepato-Biliary-Pancreatic Surgery
• /
• v.26 no.1
• /
• pp.84-90
• /
• 2022

Backgrounds/Aims: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) remains a dreadful complication. Duct-to-mucosa pancreaticojejunostomy (DTMPJ) is a commonly performed anastomosis after PD. This study aims to evaluate whether there is a size limit of pancreatic duct below which POPF rate increases significantly after DTMPJ. Methods: A retrospective study was performed from a database with prospectively collected data on consecutive patients undergoing DTMPJ. Results: Between the years 2003 and 2019, a total of 288 patients with DTMPJ were recruited. POPF occurred in 56.3% of the patients, of which 43.8% were biochemical leak, 8.7% were grade B, and 1.4% were grade C. Overall operative morbidity was 51.4%, of which 19.1% were major complications. Five patients (1.7%) died within 90 days of operation. Patients with grade B/C POPF had significantly soft pancreas (p < 0.001), smaller duct size (p = 0.031), and a diagnosis of carcinoma of the pancreas (p = 0.027). When a clinically significant POPF rate was analysed based on the pancreatic duct diameter, pancreatic duct size ≤ 1 mm had the highest POPF rate (35.7%). There was a significant difference in POPF rate between adjacent ductal diameter ≤ 1 mm and > 1 mm to 2 mm (35.7% vs 13.3%; p = 0.040). Multivariable analysis showed that for the soft pancreas, pancreatic duct diameter ≤ 1 mm was the only significant predictive factor for POPF (p = 0.027). Conclusions: DTMPJ can be safely performed for pancreatic duct > 1 mm without significantly increased POPF risk.

• Molecules and Cells
• /
• v.37 no.12
• /
• pp.888-898
• /
• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

• Journal of the Korean Society of Radiology
• /
• v.82 no.3
• /
• pp.638-653
• /
• 2021

Purpose To compare the recurrence pattern, disease-free survival (DFS), and overall survival (OS) after curative surgery for pancreatic ductal adenocarcinoma (PDAC) in patients who underwent preoperative evaluation with CT alone or in combination with MRI, and to compare the prognosis according to the first recurrence site. Materials and Methods We retrospectively evaluated 152 patients who underwent R0 resection of PDAC. Preoperative CT or combined CT and MRI were performed for 103 and 49 patients, respectively. Two radiologists recorded the location and date of the first recurrence in consensus. The recurrence pattern, DFS, and OS were compared between the two groups. OS was analyzed according to the first recurrence site. Results In both groups, liver metastasis was the most common recurrence pattern. DFS (p = 0.247) or OS (p = 0.067) showed no significant difference between the two groups. OS according to the first recurrence site was the lowest for liver metastasis, followed by locoregional recurrence (p < 0.001). Conclusion There were no significant differences in the recurrence pattern, DFS, or OS between patients evaluated with preoperative CT alone or with CT and MRI after curative resection of PDAC. Liver metastasis was the most common tumor recurrence pattern with the lowest OS.

• Korean Journal of Radiology
• /
• v.23 no.11
• /
• pp.1055-1066
• /
• 2022

Objective: The clinical relevance of myosteatosis has not been well evaluated in patients with pancreatic ductal adenocarcinoma (PDAC), although sarcopenia has been extensively researched. Therefore, we evaluated the prognostic value of muscle quality, including myosteatosis, in patients with resectable PDAC treated surgically. Materials and Methods: We retrospectively evaluated 347 patients with resectable PDAC who underwent curative surgery (mean age ± standard deviation, 63.6 ± 9.6 years; 202 male). Automatic muscle segmentation was performed on preoperative computed tomography (CT) images using an artificial intelligence program. A single axial image of the portal phase at the inferior endplate level of the L3 vertebra was used for analysis in each patient. Sarcopenia was evaluated using the skeletal muscle index, calculated as the skeletal muscle area (SMA) divided by the height squared. The mean SMA attenuation was used to evaluate myosteatosis. Diagnostic cutoff values for sarcopenia and myosteatosis were devised using the Contal and O'Quigley methods, and patients were classified according to normal (nMT), sarcopenic (sMT), myosteatotic (mMT), or combined (cMT) muscle quality types. Multivariable Cox regression analyses were conducted to assess the effects of muscle type on the overall survival (OS) and recurrence-free survival (RFS) after surgery. Results: Eighty-four (24.2%), 73 (21.0%), 75 (21.6%), and 115 (33.1%) patients were classified as having nMT, sMT, mMT, and cMT, respectively. Compared to nMT, mMT and cMT were significantly associated with poorer OS, with hazard ratios (HRs) of 1.49 (95% confidence interval, 1.00-2.22) and 1.68 (1.16-2.43), respectively, while sMT was not (HR of 1.40 [0.94-2.10]). Only mMT was significantly associated with poorer RFS, with an HR of 1.59 (1.07-2.35), while sMT and cMT were not. Conclusion: Myosteatosis was associated with poor OS and RFS in patients with resectable PDAC who underwent curative surgery.

• Journal of Trauma and Injury
• /
• v.24 no.2
• /
• pp.136-142
• /
• 2011

Purpose: Blunt pancreatic injury has a high mortality rate, especially if adequate management is delayed. Although many guidelines exist for diagnosis and treatment, there is no consensus to date. Therefore, we analyzed the role of endoscopic retrograde cholangiopancreatography (ERCP) as a diagnostic and therapeutic tool for the treatment of traumatic pancreatic injury. Methods: We retrospectively reviewed the electronic medical records (EMR) database at Asan Medical Center (Seoul, South Korea) to identify all patients diagnosed with trauma to the pancreas between June 2003 and December 2010. Clinical and operative findings, CT (computed tomography) images, and ERCP findings were assessed. Results: A total of 40 patients were evaluated in this study. Of these, 14 patients underwent diagnostic ERCP, and 26 did not. Of the 14 patients who underwent diagnostic ERCP, 5 were found to have normal pancreatic ducts, thereby preventing a needless laparotomy in these patients. Of the patients diagnosed with ductal injury, four were treated with endoscopic intervention, and four underwent an exploratory laparotomy. The remaining patient was treated with radiologic intervention (percutaneous drainage) to manage pancreatic pseudocyst formation. Conclusion: Our findings suggest that ERCP is a beneficial diagnostic and therapeutic modality for the treatment of traumatic pancreatic injury.