Impact of Nrf2 overexpression on cholangiocarcinoma treatment and clinical prognosis

Purpose@#Nrf2 regulates antioxidant protein expression and protects against drug toxicity and oxidative stress, whereas Keap1 controls Nrf2 activity. The Keap1-Nrf2 pathway affects the prognosis of various cancers, however, its effect on cholangiocarcinoma chemoresistance and prognosis remains unclear. This study aimed to determine whether the Keap1-Nrf2 pathway affects chemoresistance and prognosis of distal cholangiocarcinoma. @*Methods@#We investigated the correlation between Nrf2 and Keap1 expression and clinical characteristics and prognosis in 91 patients with distal cholangiocarcinoma who underwent curative surgery. Immunohistochemical staining was performed on paraffin blocks using primary antibodies against Nrf2 and Keap1. The relationship between Keap1 and Nrf2 protein expression levels, and clinical characteristics and prognosis was examined. @*Results@#Nrf2 expression was not associated with overall survival in patients who did not receive adjuvant chemotherapy (P=0.994). Among patients receiving adjuvant chemotherapy, the Nrf2 low expression group had a significantly longer median overall survival than the Nrf2 high expression group in Kaplan-Meier survival analysis (P=0.019). In multivariate analysis, high expression of Nrf2 was confirmed as an independent poor prognostic factor in the group receiving adjuvant chemotherapy (P=0.041). @*Conclusion@#This study suggests that Nrf2 overexpression reduces the efficacy of adjuvant chemotherapy in distal cholangiocarcinoma.

Imaging Findings of an Intraluminal Duodenal Diverticulum Associated with Adult Duodeno-Duodenal Intussusception and Recurrent Pancreatitis: A Case Report

Intraluminal duodenal diverticulum (IDD) is a rare congenital abnormality, consisting of a sac-like mucosal lesion in the duodenum. Cases of IDD can present with gastrointestinal bleeding, duodenal obstruction, or pancreatitis. Here, we report a rare case of a 25-year-old female presenting with IDD complicated by duodeno-duodenal intussusception and recurrent pancreatitis. The diagnosis was based on findings from radiologic examinations (CT and MRI), upper gastrointestinal series (barium swallow), and gastroduodenofiberscopy. Laparoscopic excision of the presumed duodenal duplication was performed. The subsequent histopathologic evaluation of the excised sac revealed normal mucosa on both sides, but the absence of a proper muscle layer confirmed the diagnosis of IDD. Radiologic detection of a saccular structure in the second portion of the duodenum can indicate IDD with duodeno-duodenal intussusception as the lead point

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP)

Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Risk factors of recurrence following common bile duct exploration for choledocholithiasis

Purpose@#The purpose of this study was to investigate the recurrence factors of choledocholithiasis after common bile duct (CBD) exploration. @*Methods@#From January 2000 to December 2018, we retrospectively reviewed 253 patients who underwent CBD exploration surgery. We excluded 100 cases who had residual stone, combined major surgery, or follow-up loss after surgery. Total of 153 patients were included, and we investigated the recurrence factors of choledocholithiasis. Various variables such as patients’ demographics, gallstones, preoperative endoscopic treatment, and laboratory data were analyzed to find factors related to recurrent choledocholithiasis. @*Results@#The median follow-up period was 20.6 months (range 4.7–219 months), and 27 patients (17.6%) had experienced recurrent choledocholithiasis. Univariate analysis showed that the following variables were associated with recurrence of choledocholithiasis; preoperative leukocytosis (white blood cell ≥ 11,000/µL), open procedure, T tube insertion, long hospital duration, and long operation time. Logistic regression multivariate analysis identified preoperative leukocytosis (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.21–9.73; p = 0.021), open procedure (OR, 5.54; 95% CI, 4.73–6.35; p = 0.037), and T-tube insertion (OR, 2.82; 95% CI, 1.04–7.65; p = 0.042) as independent predictors of recurrent choledocholithiasis. @*Conclusion@#Because of delayed recurrence of choledocholithiasis, it is recommended to continue follow-up of patients after CBD exploration surgery. Laparoscopic surgery was observed to be associated with a reduction in recurrence. The preoperative leukocytosis and clinical conditions in which open surgery is performed could be associated with recurrence of choledocholithiasis. However, further study is necessary to validate the result.

Nutritional risk factors are associated with postoperative complications after pancreaticoduodenectomy

PURPOSE: The purpose of this study was to investigate whether the indicators of nutritional risk screening tool are associated with postoperative complications following pancreaticoduodenectomy (PD). METHODS: We investigated whether nutritional risk is associated with postoperative complications based on the medical records of 128 patients who underwent PD from 2010. The tool was composed of 6 risk factors: albumin, total lymphocyte count, body mass index, weight loss, dietary intake loss, and nutritional symptoms. The patients were divided into 2 groups: a nutritional risk group and a nonrisk group. The rates of general complications and postoperative pancreatic fistula (POPF) were investigated according to this nutritional status. RESULTS: There were 65 patients who did not have any risk factors. However, 63 patients had one risk factor or more. In the nonrisk group, the overall complication rate and serious complication rate were 30.8% and 15.4%, respectively. If there were one or more risk factors, the overall and serious complication rates were 59.5% and 41.3%, respectively (P = 0.001 and P = 0.001, respectively). The rate of clinically relevant POPF (grade B or C) was 9.2% in the nonrisk group. However, this rate was 23.8% in the NRS risk group (P = 0.029). In multivariate analysis, the NRS risk group was a significant factor of clinically relevant POPF (odds ratio, 9.878; 95% confidence interval, 1.527–63.914; P = 0.016). CONCLUSION: There were statistically significant associations between complications and nutritional indicators. A comprehensive analysis of nutritional parameters will help predict postoperative complications.

Bile duct segmental resection versus pancreatoduodenectomy for middle and distal common bile duct cancer

PURPOSE: To compare survival outcomes between bile duct segmental resection (BDR) and pancreatoduodenectomy (PD) for the treatment of middle and distal bile duct cancer. METHODS: From 1997 to 2013, a total of 96 patients who underwent curative intent surgery for middle and distal bile duct cancer were identified. The patients were divided into 2 groups based on the type of operation; 20 patients were included in the BDR group and 76 patients were in the PD group. We retrospectively reviewed the clinical outcomes. RESULTS: The number of lymph nodes (LNs) was significantly greater in patients within the PD group compared to the BDR group. The total number of LNs was 6.5 ± 8.2 vs. 11.2 ± 8.2 (P = 0.017) and the number of metastatic LNs was 0.4 ± 0.9 vs. 1.0 ± 1.5 (P = 0.021), respectively. After a median follow-up period of 24 months (range, 4–169 months), the recurrence-free survival of the PD group was superior to that of the BDR group (P = 0.035). In the patients with LN metastases, the patients undergoing PD had significantly better survival than the BDR group (P < 0.001). CONCLUSION: Surgeons should be cautious in deciding to perform BDR for middle and distal common bile duct cancer. PD is recommended if LN metastases are suspected.

Extended versus peripancreatic lymph node dissection for the treatment of left-sided pancreatic cancer

PURPOSE: The pathways of lymphatic metastases differ according to the tumor location in pancreatic cancer patients. However, it is unclear whether extended lymph node dissection (LND) is essential for all left-sided pancreatic cancer. The aim of this study is to evaluate the survival outcomes according to the extent of LND and tumor location in patients with left-sided pancreatic cancer. METHODS: January 2005 to December 2013, we retrospectively identified 107 patients who underwent curative intent surgery for left-sided pancreatic cancer. The left-sided pancreatic cancer was defined as a tumor located in pancreatic body or tail. The extent of LND was divided into 2 groups: extended LND and peripancreatic LND. The extended LND group included celiac and superior mesenteric LNs. RESULTS: We included 107 patients with left-sided pancreatic cancer; 59 patients with pancreatic body cancer and 48 patients with pancreatic tail cancer. The median follow-up period was 17 months (range, 3–110 months). Fifty patients with pancreatic body cancer and 30 patients with pancreatic tail cancer underwent extended LND. In patients with pancreatic body cancer, extended LND was associated with improved disease-free survival (DFS) (P = 0.010) and overall survival (P = 0.014). However, extended LND was not associated with DFS in patients with pancreatic tail cancer. CONCLUSION: Extended LND could improve survival in patients with pancreatic body cancer. However, extended LND had no survival benefit for the treatment of pancreatic tail cancer.

Validation of international consensus guideline 2012 for intraductal papillary mucinous neoplasm of pancreas

PURPOSE: Intraductal papillary mucinous neoplasm (IPMN) has variable malignant potential ranging from premalignant intraductal lesions to malignant neoplasms with invasive carcinoma. To help physicians managing patients with IPMN, International consensus guidelines was made in 2006 and revised in 2012. This study was designed to evaluate the clinical usefulness of guidelines and to validate. METHODS: From October 1996 to December 2011, we retrospectively reviewed the data of 230 patients who underwent pancreatic resection for IPMN. Univariate and multivariable analyses were used to identify significant predictors of malignancy in IPMN. RESULTS: Of the 230 patients, 62 patients (27%) were diagnosed with invasive carcinoma. Jaundice (P < 0.001; 95% confidence interval [CI], 3.086-40.010) main pancreatic duct diameter equal to or greater than 10 mm (P < 0.001; 95% CI, 1.723-6.673) and also abdominal pain (P < 0.001; 95% CI, 4.363-22.600) show statistical significance in univariate and multivariate analysis. "High-risk stigmata" was statistical powerful predictors of malignancy than "worrisome features". International consensus guidelines 2012 had improvement on specificity but deterioration of sensitivity. CONCLUSION: Revised guidelines seemed to bring about an improvement of weak side of Sendai criteria. Abdominal pain, jaundice, main pancreas duct greater than 10 mm can be clinical variables to predict malignancy.

Safety and Feasibility of Single Incision Laparoscopic Spleen Preserving Distal Pancreatectomy

PURPOSE: Single-incision laparoscopic distal pancreatectomy (SIL-DP) has recently been attempted in the treatment of left-sided benign neoplasms of the pancreas. This study was conducted to evaluate the perioperative outcomes of SIL-DP compared with conventional laparoscopic DP (CL-DP). METHODS: Patients who received laparoscopic DP from a single surgeon for benign pancreatic neoplasm from January 2012 to January 2014 were included. The patients were divided into two groups, SIL-DP and CL-DP. We used four trocars for CL-DP and a custom-made glove port for SILDP and analyzed the conversion cases separately. Perioperative outcomes were compared between types of surgery. RESULTS: SIL-DP was attempted in 13 patients, five of whom required conversion to CL-DP or dual-incision surgery. CL-DP was attempted in 27 patients and all were successful without open conversion. The spleen was preserved in all patients who underwent SIL-DP without conversion, in four of five (80%) in the conversion group, and 21 (78%) of those who underwent CL-DP. The complication rate was 13% in the SIL-DP-only group, 60% in the conversion group, and 19% in the CL-DP group. The operation time, estimated blood loss, numeric pain intensity score, and hospital duration were similar in the SIL-DP and CL-DP groups. CONCLUSION: SIL-DP was associated with a moderate need for an additional port, and the complication rate was high in the conversion group. Our findings indicate that SIL-DP should be attempted carefully. Further studies are needed to evaluate the lon g term follow-up outcomes of SIL-DP.

The safety and risk factors of major hepatobiliary pancreatic surgery in patients older than 80 years

PURPOSE: Recently, the number of elderly patients has increased due to a longer life expectancy. Among these elderly patients, more octogenarians will be diagnosed with major hepatobiliary pancreatic (HBP) diseases. Therefore, we need to evaluate the safety and risk factors of major HBP surgery in patients older than 80 years. METHODS: From January 2000 to April 2015, patients who underwent major HBP surgery were identified. The patients were divided into 2 groups according to their age at the time of surgery: Group O (≥80 years) and group Y (<80 years). The patient characteristics and intra- and postoperative outcomes were retrospectively investigated in the 2 groups. RESULTS: The median age was 84 years (range, 80–95 years) in group O and 61 years (range, 27–79 years) in group Y. group O had worse American Society of Anesthesiologists (ASA) physical status (ASA ≥ III: 23% vs. 7%, P = 0.002) and was associated with a higher rate of hypertension and heart problems as comorbidities. There were significant differences in albumin and BUN, favoring group Y. The length of intensive care unit stay was longer in group O, whereas the overall complication and mortality rates did not show statistical difference. But, there was a significant difference in systemic complication of both Clavien-Dindo classification grade ≥II and ≥III as complications were divided into surgical site complication and systemic complication. CONCLUSION: Major HBP surgery can be performed safely in patients older than 80 years if postoperative management is appropriately provided.