Search

Background: Process-based quality metrics are important for improving long-term outcomes after surgical resection. We sought to develop a practical surgical quality score for patients diagnosed with pancreatic ductal adenocarcinoma undergoing curative-intent resection., Methods: Patients who underwent surgical resection for pancreatic ductal adenocarcinoma between 2010 and 2017 were identified using the National Cancer Database. Five surgical quality metrics were defined: minimally invasive approach, adequate lymphadenectomy, negative surgical margins, receipt of adjuvant therapy, and no prolonged hospitalization. Log-rank test and multivariable Cox regression analysis were used to determine the association of quality metrics with overall survival., Results: A total of 38,228 patients underwent curative-intent resection for pancreatic ductal adenocarcinoma. Median age at diagnosis was 68 years (interquartile range = 61-75), and roughly half the cohort was male (n = 19,562; 51.2%). Quality metrics were achieved on a varied basis: minimally invasive approach (n = 5,701; 14.9%), adequate lymphadenectomy (n = 27,122; 80.0%), negative surgical margin (n = 29,248; 76.5%), receipt of adjuvant therapy (n = 26,006; 68.0%), and absence of prolonged hospitalization (n = 26,470; 69.2%). An integer-based surgical quality score from 0 (no quality metrics) to 16 (all quality metrics) was calculated. Patients with higher scores had progressively better overall survival. Median overall survival differed substantially among the score categories (score = 0-4 points, 8.7 [8.0-9.6] months; 5-8 points, 17.5 [16.9-18.2] months; 9-12 points, 22.1 [21.6-22.8] months; and 13-16 points, 30.8 [30.2-31.3] months; P <  .001). On multivariable analysis, risk-adjusted mortality hazards decreased in a stepwise manner with higher scores (0-4 points: reference; 5-8 points: multivariable adjusted hazard ratio = 0.60; 95% CI, 0.57-0.63; 9-12 points: adjusted hazard ratio = 0.49; 95% CI, 0.47-0.52; 13-16 points: and adjusted hazard ratio = 0.37; 95% CI, 0.34-0.40; all P < .001)., Conclusion: Adherence to quality metrics may be associated with improved overall survival. Efforts aimed at increasing compliance with quality metric measures may help optimize long-term outcomes among patients undergoing surgical resection for pancreatic ductal adenocarcinoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer., Methods: 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were OS and treatment completion., Results: Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1-, 3-, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1-, 3-, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively)., Conclusion: Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Mesopancreas resection is a crucial but difficult procedure when performing pancreaticoduodenectomy. This study evaluated the influence of mesopancreas thickness on surgical outcomes in patients undergoing pancreaticoduodenectomy., Methods: We measured the thickness of the fat tissue on the right side of the superior mesenteric artery from the dorsal margin of the confluence of the superior mesenteric vein and portal vein to the ventral margin of the left renal vein on preoperative contrast-enhanced computed tomography and defined it as the mesopancreas thickness. We evaluated the correlation between mesopancreas thickness and intraoperative and postoperative variables in 357 patients who underwent pancreaticoduodenectomy., Results: Multivariate analysis revealed that a thick mesopancreas was significantly associated with a long operative time (β = 10.361; 95% confidence interval, 0.370-20.353, p = 0.042), high estimated blood loss (β = 36.038; 95% confidence interval, -27.192-99.268, p = 0.013), and a low number of resected lymph nodes (β = -1.551; 95% confidence interval, -2.662--0.439, p = 0.006). This analysis further revealed that thick mesopancreas was a significant risk factor for overall morbidity (odds ratio 2.170; 95% confidence interval 1.340-3.520, p = 0.002), major morbidity (odds ratio 2.430; 95% confidence interval 1.360-4.340, p = 0.003), and a longer hospital stay (β = 2.386; 95% confidence interval 0.299-4.474, p = 0.025)., Conclusion: A thick mesopancreas could predict a longer operation time, higher estimated blood loss, fewer resected lymph nodes, more frequent overall and major morbidities, and a longer hospital stay in patients who underwent pancreaticoduodenectomy more precisely than the body mass index., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult., Methods: Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated., Results: In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure., Conclusions: PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Pancreatic cancer (PDAC) requires a multimodality approach. We sought to define the association between social determinants of health (SDOH) and delayed or nonreceipt of adjuvant chemotherapy (aCT) among patients undergoing PDAC resection., Methods: Data on patients who underwent PDAC resection between 2014 and 2020 were identified from Medicare Standard Analytic Files and merged with the county-level social vulnerability index (SVI). Mediation analysis defined the association between SVI subthemes and aCT receipt., Results: Among 24 078 patients, 47.7% received timely aCT, 17.7% received delayed aCT, and 34.6% did not receive any aCT. High SVI was associated with delay (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.10-1.34) and nonreceipt of aCT (OR 1.30, 95% CI 1.20-1.41) (both p < 0.05). 73.1% of the variation in timely aCT receipt was directly attributable to SVI, whereas 26.9% of the effect was due to indirect mediators including hospital volume (6.4%), length-of-stay (7.9%) and postoperative complications (12.6%). Socioeconomic status (delayed aCT: OR 1.25, 95% CI 1.13-1.38; nonreceipt aCT: OR 1.25, 95% CI 1.15-1.36) and household composition and disability (delayed aCT: OR 1.30, 95% CI 1.17-1.43; nonreceipt aCT: OR 1.19, 95% CI 1.09-1.29) were associated with receipt of aCT (both p < 0.001)., Conclusions: Most of the disparities in receipt of aCT after PDAC surgery are driven by underlying SDOH such as SVI., (© 2023 Wiley Periodicals LLC.)

Background: Optimal preoperative biliary drainage for patients with pancreatic cancer before pancreatoduodenectomy remains unclear. This study aimed to investigate the comparison of efficacy and safety between a metallic stent (MS) and a plastic stent (PS)., Methods: Comparative studies on the use of MS and PS for pancreatic cancer before pancreatoduodenectomy were systematically searched using the MEDLINE and Web of Science databases. Pre- and postoperative data also were extracted. Random-effects meta-analyses were performed to compare post-endoscopic retrograde cholangiopancreatography (ERCP) complications as well as intra- and postoperative outcomes between the two arms of the study, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 percent confidence intervals (CIs)., Results: The study analyzed 12 studies involving 683 patients. Insertion of MS was associated with a lower incidence of re-intervention (OR, 0.06; 95% CI 0.03-0.15; P < 0.001), increased post-ERCP adverse events (OR, 2.22; 95% CI 1.13-4.36; P = 0.02), and similar operation time (MD, 18.0 min; 95% CI -29.1 to 65.6 min; P = 0.46), amount of blood loss (MD, 43.0 ml; 95% CI -207.1 to 288.2 ml; P = 0.73), and surgical complication rate (OR, 0.78; 95% CI 0.53-1.15; P = 0.21). The cumulative stent patency rate after 3 months was higher in the MS group than in the PS group (70-100 % vs 30.0-45.0 %)., Conclusion: For biliary drainage in patients with pancreatic cancer during this era of multidisciplinary treatment, MS use might be the first choice because MS provides a more durable biliary drainage and a similar risk of postoperative outcomes compared with PS., (© 2023. Society of Surgical Oncology.)

Background: Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection., Methods: Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test., Results: GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044)., Conclusions: Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET., (© 2023. The Author(s).)

Introduction: While Medicaid Expansion (ME) has improved healthcare access, disparities in outcomes after volume-dependent surgical care persist. We sought to characterize the impact of ME on postoperative outcomes among patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC) at high-volume (HVF) versus low-volume (LVF) facilities., Methods: Patients who underwent resection for PDAC were identified from the National Cancer Database (NCDB; 2011-2018). HVF was defined as ≥20 resections/year. Patients were divided into pre- and post-ME cohorts, and the primary outcome was textbook oncologic outcomes (TOO). Difference-in-difference (DID) analysis was used to assess changes in TOO achievement among patients living in ME versus non-ME states., Results: Among 33,764 patients who underwent resection of PDAC, 19.1% (n = 6461) were treated at HVF. Rates of TOO achievement were higher at HVF (HVF: 45.7% vs. LVF: 32.8%; p < 0.001). On multivariable analysis, undergoing surgery at HVF was associated with higher odds of achieving TOO (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.49-1.72) and improved overall survival (OS) [hazard ratio (HR) 0.96, 95% CI 0.92-0.99]. Compared with patients living in non-ME states, individuals living in ME states were more likely to achieve TOO on adjusted DID analysis (5.4%, p = 0.041). Although rates of TOO achievement did not improve after ME at HVF (3.7%, p = 0.574), ME contributed to markedly higher rates of TOO among patients treated at LVF (6.7%, p = 0.022)., Conclusions: Although outcomes for PDAC remain volume-dependent, ME has contributed to significant improvement in TOO achievement among patients treated at LVF. These data highlight the impact of ME on reducing disparities in surgical outcomes relative to site of care., (© 2023. Society of Surgical Oncology.)

Background: Access to high-quality cancer care is affected by environmental exposures and structural inequities. This study sought to investigate the association between the environmental quality index (EQI) and achievement of textbook outcomes (TO) among Medicare beneficiaries over the age of 65 who underwent surgical resection for early-stage pancreatic adenocarcinoma (PDAC)., Methods: Patients diagnosed with early-stage PDAC from 2004 to 2015 were identified using the SEER-Medicare database and combined with the US Environmental Protection Agency's EQI data. High EQI category indicated poor environmental quality, whereas low EQI indicated better environmental conditions., Results: A total of 5,310 patients were included, of which 45.0% (n = 2,387) patients achieved TO. Median age was 73 years and more than half were female (n = 2,807, 52.9%), married (n = 3,280, 61.8%), and resided in the Western region of the US (n = 2,712, 51.1%). On multivariable analysis, patients residing in moderate and high EQI counties were less likely to achieve a TO (referent: low EQI; moderate EQI: OR 0.66, 95% CI 0.46-0.95; high EQI: OR 0.65, 95% CI 0.45-0.94; p < 0.05). Increasing age (OR 0.98, 95%CI 0.97-0.99), racial minorities (OR 0.73, 95% CI 0.63-0.85), having a Charlson co-morbidity index > 2 (OR 0.54, 95%CI 0.47-0.61) and stage II disease (OR 0.82, 95%CI 0.71-0.96) were also associated with not achieving a TO (all p < 0.001)., Conclusion: Older Medicare patients residing in moderate or high EQI counties were less likely to achieve an "optimal" TO after surgery. These results demonstrate that environmental factors may drive post-operative outcomes among patients with PDAC., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Racial/ethnic disparities in pancreatic adenocarcinoma (PDAC) outcomes may relate to receipt of National Comprehensive Cancer Network (NCCN) guideline-compliant care. We assessed the association between treatment at minority-serving hospitals (MSH) and receipt of NCCN-compliant care., Patients and Methods: Patients who underwent resection of early-stage PDAC between 2006 and 2019 were identified from the National Cancer Database (NCDB). MSH was defined as the top decile of facilities treating minority ethnicities (Black and/or Hispanic). Factors associated with receipt of NCCN-compliant care and its impact on overall survival (OS) were assessed., Results: Among 44,873 patients who underwent resection of PDAC, most were treated at non-MSH (n = 42,571, 94.9%), while a smaller subset were treated at MSH (n = 2302, 5.1%). Patients treated at MSH were more likely to be at a younger median age (MSH 66 years versus non-MSH 67 years), Black or Hispanic (MSH 58.4% versus non-MSH 12.0%), and not insured (MSH 7.8% versus non-MSH 1.6%). While 71.7% (n = 31,182) of patients were compliant with NCCN care, guideline-compliant care was lower at MSH (MSH 62.5% versus non-MSH 72.2%). On multivariable analysis, receiving care at MSH was associated with not receiving guideline-compliant care [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.74]. At non-MSH, non-white patients had lower odds of receiving guideline-compliant PDCA care (OR 0.85, 95% CI 0.78-0.91). Failure to comply was associated with worse overall survival (OS) [hazard ratio (HR) 1.50, 95% CI 1.46-1.54, all p < 0.001]., Conclusions: Patients with PDAC treated at MSH and minorities treated at non-MSH were less likely to receive NCCN-compliant care. Failure to comply with guideline-based PDAC treatment was associated with worse OS., (© 2023. Society of Surgical Oncology.)

Aim: The number of surgeries for pancreatic ductal adenocarcinoma (PDAC) in older adults has been rising. This study aimed to evaluate the technical and oncological safety of pancreatectomy for older adults aged ≥75 years with PDAC by retrospectively comparing their short- and long-term outcomes with those of younger adults aged <75 years., Methods: Data were collected from 117 patients who underwent pancreatectomy for PDAC in our department. The indication for surgery regarding patient characteristics was considered according to each patient's American Society of Anesthesiologists physical status and Eastern Cooperative Oncology Group Performance Status Scale. Data of older adults (n = 32) were compared with those of younger adults (n = 85), and comprised patient background, surgical factors, postoperative course, histopathological factors and prognostic factors. Additionally, prognostic nutritional index values preoperatively and at 1 and 6 months postoperatively were compared between the two groups., Results: Although American Society of Anesthesiologists physical status and comorbidities were worse in older adults, there were no significant differences in surgical factors, postoperative courses and histopathological factors between the two groups. The overall complication rate tended to be higher in older adults (40.6%) than in younger adults (29.4%). There were no differences in median lengths of recurrence-free survival and overall survival (older adults vs younger adults: 12 vs 13 months, P = 0.545, and 26 vs 20 months, P = 0.535, respectively) between the two groups. Furthermore, no significant differences were found in prognostic nutritional index preoperatively to 6 months after surgery., Conclusion: With careful determination of surgical indications, pancreatectomy for PDAC can be carried out with acceptable post-pancreatectomy morbidity in younger adults. Geriatr Gerontol Int 2023; 23: 531-536., (© 2023 Japan Geriatrics Society.)

Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable disease; mPD, progressive disease. Of 61 patients, 14 diagnosed with PD after initial CT imaging showed significantly worse therapeutic outcomes than 47 patients with disease control. In these 47 patients, initial molecular assessment exhibited significant differences in therapeutic outcomes between patients with and without ctDNA (mPD + mSD vs. mCR + mNT; 13.2 M vs. 21.7 M, P = 0.0029) but no difference between those with mPD and mSD + mCR + mNT, suggesting that the presence of ctDNA had more impact on the therapeutic outcomes than change in its number. Multivariate analysis revealed that it was the only independent prognostic factor (P = 0.0405). The presence of ctDNA in initial molecular assessment predicted early tumor progression and identified PC patients more likely to benefit from chemotherapy., (© 2023. The Author(s).)

Genome‑wide DNA hypomethylation is the most common molecular feature in human cancers associated with chromosomal instability (CIN), which is involved in the mechanisms that regulate pancreatic cancer (PC) metastasis. It was investigated whether genome‑wide DNA hypomethylation affects the phenotype in PC via CIN in vitro , and its significance on the biological behavior of PC was verified. The relative demethylation level (RDL) of long interspersed nucleotide element‑1 (LINE‑1) in human PC cell lines was used to characterize DNA hypomethylation using methylation‑specific quantitative (q)PCR. CIN was estimated by changes in chromosomal copy number using comparative genomic hybridization analysis. Abnormal segregation of chromosomes was assessed by immunocytochemistry, and the DNA damage response was evaluated using the number of anti‑γH2AX positive cells. Invasion ability was assessed using a Matrigel invasion assay. Clinical specimens from 49 patients with PC who underwent curative surgery were evaluated for a correlation of DNA hypomethylation with clinical outcome. Successful induction of genome‑wide DNA hypomethylation in PC cells led to copy number changes in specific chromosomal regions. The number of cells with abnormal segregation of chromosomes significantly increased with the number of anti‑γH2AX positive cells. The invasive potential of these cells also significantly increased. The occurrence of occult distant metastasis in the clinical specimens and receiver operating characteristic analysis clearly identified those who were and were not likely to have occult distant metastasis, with high LINE‑1 RDL significantly correlated with the presence of occult distant metastasis (P=0.035) and poor prognosis (P=0.048). The significance of genome‑wide DNA hypomethylation on the biological behavior of PC, which promotes a more invasive phenotype via CIN in vitro and predicts the susceptibility to occult distant metastasis and poor prognosis in patients with PC was revealed.

Peritoneal dissemination of pancreatic cancer has a poor prognosis. We have reported that intraperitoneal radioimmunotherapy using a 64 Cu-labeled antibody ( 64 Cu-ipRIT) is a promising adjuvant therapy option to prevent this complication. To achieve personalized 64 Cu-ipRIT, we developed a new in vitro tumor cell-binding assay ( 64 Cu-TuBA) system with a panel containing nine candidate 64 Cu-labeled antibodies targeting seven antigens (EGFR, HER2, HER3, TfR, EpCAM, LAT1, and CD98), which are reportedly overexpressed in patients with pancreatic cancer. We investigated the feasibility of 64 Cu-TuBA to select the highest-binding antibody for individual cancer cell lines and predict the treatment response in vivo for 64 Cu-ipRIT. 64 Cu-TuBA was performed using six human pancreatic cancer cell lines. For three cell lines, an in vivo treatment study was performed with 64 Cu-ipRIT using high-, middle-, or low-binding antibodies in each peritoneal dissemination mouse model. The high-binding antibodies significantly prolonged survival in each mouse model, while low-and middle-binding antibodies were ineffective. There was a correlation between in vitro cell binding and in vivo therapeutic efficacy. Our findings suggest that 64 Cu-TuBA can be used for patient selection to enable personalized 64 Cu-ipRIT. Tumor cells isolated from surgically resected tumor tissues would be suitable for analysis with the 64 Cu-TuBA system in future clinical studies.

Purpose: To compare the outcomes of laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) with those of open RAMPS (O-RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: We reviewed, retrospectively, the medical records of 50 patients who underwent RAMPS for PDAC without resection of major vessels and adjacent organs between 2007 and 2019, and analyzed the relationship between the operative method and surgical and oncological outcomes., Results: Nineteen of the 50 patients underwent L-RAMPS and 31 patients underwent O-RAMPS. L-RAMPS was associated with significantly less blood loss (P = 0.034) but a longer operative time (P = 0.001) than O-RAMPS. There were no significant differences in patient characteristics, tumor factors, or postoperative course; or in the rates of recurrence-free survival (P = 0.084) or overall survival (P = 0.402) between the L-RAMPS and O-RAMPS groups., Conclusion: L-RAMPS for PDAC resulted in less blood loss but a longer operative time than O-RAMPS. Although L-RAMPS may be feasible, the operative time needs to be reduced by standardizing the procedure., (© 2021. Springer Nature Singapore Pte Ltd.)

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery., (© 2021. The Author(s).)

Background: The treatment strategy for pancreatic metastasis (PM) from renal cell carcinoma (RCC) is unclear due to its rarity. The aim of this study was to reveal the role of surgery for PM from RCC., Methods: A systematic literature search was conducted using PubMed and the Cochrane Library. The effectiveness of surgery for PM was evaluated based on the primary outcome of overall survival (OS), which was investigated in relation to surgical procedures and metastatic sites via subgroup analyses., Results: There was no significant difference in the rate of 2-year OS between the surgery and control group (OR 0.43, 95% CI 0.14-1.26, P = 0.12). However, the rate of 5-year OS was significantly higher in the surgery group than the control group (OR = 0.41, 95% CI 0.18-0.93, P = 0.03). The rates of the complications and OS were not significantly different between radical and conservative pancreatectomies. The rate of 5-year OS of the patients with PM was higher than that with other metastases (OR 0.38, 95% CI 0.20-0.74, P = 0.004)., Conclusion: Surgical resection for PM from RCC is associated with good prognosis. Limited surgery may be a useful option depending on the location of the lesion.

Purpose: Although the same distal pancreatectomy (DP) is performed regardless of the location of left-sided pancreatic ductal adenocarcinoma (PDAC), the clinicopathological features may differ depending on the tumor location. The present study investigated the relationship between the tumor location and clinicopathological features in patients with left-sided PDAC., Methods: The records of 59 patients who underwent DP for PDAC were enrolled. The relationship between the tumor location and clinicopathological features was investigated. The tumor location was classified into three groups according to the 7th AJCC/UICC TNM classification: body (Pb), body and tail (Pbt), and tail (Pt)., Results: Tumors were located at the Pb in 26 patients, Pbt in 15, and Pt in 18. There was no metastasis to the lymph nodes around the common hepatic artery in Pt. The rate of peritoneal dissemination in the Pt was higher than that in the Pb (P = 0.034) or Pbt (P = 0.002). There were no significant differences in the overall survival among the three groups., Conclusion: There was no metastasis to the lymph nodes around the common hepatic artery, and peritoneal dissemination was the most common site of recurrence in Pt tumors.

Some reports have shown that the prognosis of recurrent lung metastases after resection of pancreatic cancer is better than that for other organs. We report on 2 cases of long‒term survival after lung resection for lung metastases from pancreatic cancer. Case 1: A 73‒year‒old man underwent distal pancreatectomy for pancreatic body cancer. Adjuvant chemotherapy of S‒1 was administered for 6 months. At 3 years after surgery, 2 small metastatic nodules were detected in the right lung, and the patient underwent thoracoscopic right upper lobectomy. At 5 years and 9 months after the initial surgery, he is alive without recurrence. Case 2: An 81‒year‒old woman underwent pylorus‒preserving pancreatoduodenectomy for pancreatic head cancer. Adjuvant chemotherapy of S‒1 was administered for 4 months. At 1 year and 9 months after surgery, a metastatic nodule was detected in the left upper lung, and the patient underwent thoracoscopic left upper lobectomy. At 4 years and 6 months after initial surgery, radiation therapy was performed for localized bone metastasis. At 5 years and 1 month after the initial surgery, she is alive without other recurrences. In conclusion, recurrent lung metastases of pancreatic cancer with a small number of metastases may result in long‒term survival following resection.

Purpose: The present study was conducted to clarify the clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma (PDAC)., Methods: Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analyzed fresh-frozen tissues from an initial cohort (17 samples of normal control pancreatic tissue [C] from 17 patients without PDAC, and 34 samples of non-cancerous pancreatic tissue [N] and 82 samples of cancerous tissue [T] both obtained from 82 PDAC patients) and formalin-fixed paraffin-embedded T samples from 34 patients in a validation cohort., Results: The DNA methylation profiles of N samples tended to differ from those of C samples, and 91,907 probes showed significant differences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was significantly correlated with a larger tumor diameter and early recurrence (ER), defined as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fixed paraffin-embedded surgically resected materials regardless of their tumor cell content, were identified for prediction of ER. The sensitivity and specificity for detection of patients belonging to the ER group using a panel combining these three marker CpG sites, including a CpG site in the CDK14 gene, were 81.8% and 71.7% and 88.9% and 70.4% in the initial and validation cohorts, respectively., Conclusion: These findings indicate that DNA methylation alterations may have a clinicopathological impact on PDAC. Application of our criteria will ultimately allow prediction of ER after surgery to improve the outcome of PDAC patients.

Background: Synovial sarcoma is a soft tissue malignancy that frequently affects the extremities, adjacent to the large joints. Synovial sarcoma has a high rate of distant metastasis; however, pancreatic metastasis is extremely rare, and to our knowledge, there has been no report of bleeding due to spontaneous tumor rupture. This study reports the case of a patient with synovial sarcoma pancreatic metastasis causing tumor rupture and bleeding, which was successfully managed with emergent distal pancreatectomy., Case Presentation: A 27-year-old woman underwent extensive resection of the primary tumor and partial lung resection after chemotherapy for left femoral synovial sarcoma and multiple lung metastases 4 years prior. During the follow-up, a 35-mm tumor was noted in the pancreatic tail on abdominal computed tomography (CT), and no other distant metastases were detected via positron emission tomography CT. Laparoscopic distal pancreatectomy was scheduled for pancreatic metastasis of synovial sarcoma. However, before the scheduled pancreatectomy could be conducted, the patient visited the emergency department because of abdominal pain that occurred after consuming a small amount of alcohol, and CT showed ascites with high CT values and leakage of contrast media. She was diagnosed with intra-abdominal hemorrhage due to a ruptured metastatic pancreatic tumor, and an emergency operation was performed. In total, 1500 mL of blood was evacuated from the abdomen, and the bleeding pancreatic tail tumor was resected. Histopathological findings revealed synovial sarcoma metastasis and a ruptured tumor capsule, and tumor cells were observed in the hematoma. After discharge on postoperative day 18, the patient was carefully monitored and confirmed to be in relapse-free survival, without chemotherapy, at 6 months post-surgery., Conclusions: While the rate of tumor growth varies depending on the grade of the tumor, the possibility of rupture should be considered even in metastatic pancreatic tumors. In the case of pancreatic tumor rupture with stable circulation, radiological evaluation for oncology is necessary, and primary resection may be compatible with resectable cases.

Epithelial‑mesenchymal transition (EMT) is considered a crucial event in the development of cancer metastasis. Metformin is a drug used in the treatment of type 2 diabetes. Recently, increasing evidence has indicated that metformin possesses anti‑tumor activities. However, the effects of metformin on EMT and metastases in pancreatic cancer remain unknown. Thus, the present study investigated whether metformin inhibits EMT of human pancreatic cancer cell lines. Pancreatic cancer cells were stimulated with transforming growth factor β1 (TGF‑β1), an activator of EMT signaling, with or without metformin. After 48 h, the levels of epithelial and mesenchymal markers were evaluated by western blot analysis, immunocytochemistry and RT‑qPCR. Cancer cell migration was evaluated by an in vitro wound healing assay. The cells stimulated with TGF‑β1 acquired an elongated and fusiform morphology, which was inhibited by metformin. The wound healing assay revealed that metformin significantly suppressed the TGF‑β1‑stimulated migration of pancreatic cancer cells. Following treatment with metformin, E‑cadherin expression (epithelial marker) was upregulated, and the levels of mesenchymal markers were downregulated, which had been increased by TGF‑β1 in these cells. Exposure of the cells to TGF‑β1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF‑β1‑induced‑EMT through the down‑regulation of the Smad pathway in PANC‑1 cells and the downregulation of the Akt/mTOR pathway in BxPC‑3 cells. In an animal model of surgical orthotopic implantation, metformin inhibited liver metastasis without a significant reduction in the size of the primary pancreatic tumor. On the whole, the findings of the present study suggest that metformin inhibits EMT and cancer metastasis through the Smad or Akt/mTOR pathway.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is an aggressive malignancy associated with poor prognosis because of recurrence, metastasis, and treatment resistance. Aberrant glycosylation of cancer cells triggers their migration and invasion and is considered one of the most important prognostic cancer biomarkers. The current study aimed to identify glycan alterations and their relationship with the malignant potential of PDAC., Methods: Using a lectin microarray, we evaluated glycan expression in 62 PDAC samples. Expression of fucosyltransferase 8 (FUT8), the only enzyme catalyzing core fucosylation, was investigated by immunohistochemistry. The role of FUT8 in PDAC invasion and metastasis was confirmed using an in vitro assay and a xenograft peritoneal metastasis mouse model., Results: The microarray data demonstrated that core fucose-binding lectins were significantly higher in carcinoma than in normal pancreatic duct tissues. Similarly, FUT8 protein expression was significantly higher in carcinoma than in normal pancreatic duct tissues. High FUT8 protein expression was significantly associated with lymph-node metastases and relapse-free survival. FUT8 knockdown significantly reduced the invasion in PDAC cell lines and impaired peritoneal metastasis in the xenograft model., Conclusions: The findings of this study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.

Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC., Methods: Forty-two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors., Results: Twenty-two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% [16/22]) was significantly superior to RECIST (36.4% [8/22]) (P = .017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut-off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates < 50% were independent predictors for relapse-free survival (hazard ratio [HR], 3.92; P = .044) and overall survival (HR, 14.08; P = .023)., Conclusions: PERCIST was more accurate in determining NAT's therapeutic effects for PDAC than RECIST. MTV reduction rates were independent prognostic factors for PDAC., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Liquid biopsies enable the detection of circulating tumor DNA (ctDNA). However, the clinical significance of KRAS-mutated ctDNA for pancreatic cancer has been inconsistent with respect to its prognostic and predictive potential., Methods and Findings: A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS mutation in tissues and KRAS ctDNA levels in plasma were determined by RASKET and droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and for evaluating therapeutic responses to chemotherapy compared with carbohydrate antigen 19-9 (CA19-9). In 67 tumor tissues, discrepancies in point mutations of KRAS were rarely observed among individual patients, implying that one targeted point mutation of KRAS can be determined in tumor tissues prior to longitudinal blood monitoring. One-time blood assessment of KRAS-mutated ctDNA before surgery or chemotherapy was not clearly associated with recurrence and prognosis. Sequential blood monitoring was performed in 39 patients who underwent surgery for potentially resectable tumors. Increased CA19-9 levels were significantly associated with recurrence, but not prognosis (P<0.001, P = 1.0, respectively), whereas emergence of KRAS ctDNA was significantly associated with prognosis (P<0.001) regardless of recurrence. Furthermore, in 39 patients who did not undergo surgery, detection of KRAS ctDNA was a predictive factor for prognosis (P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA was the only independent prognostic factor regardless of tumor resection (hazard ratios = 54.5 for patients who underwent surgery and 10.1 for patients who did not undergo surgery; P<0.001 for both). Patients without emergence of KRAS ctDNA within 1 year after surgery showed significantly better prognosis irrespective of recurrence (P<0.001). No detection or disappearance of KRAS ctDNA within 6 months of treatment was significantly correlated with therapeutic responses to first-line chemotherapy (P<0.001). Changes in KRAS status provided critical information for the prediction of therapeutic responses., Conclusions: Our study showed for the first time that detection of KRAS ctDNA levels within a short period enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer., Competing Interests: The authors have declared that no competing interests exist.

The abundance of cytotoxic T-cell infiltrates has important implications for patient outcome and therapeutic design for pancreatic ductal adenocarcinoma. However, intratumoral heterogeneity remains a challenge to understanding the complex immune microenvironment. We hypothesized that characterizing CD8 + cell distribution within pancreatic adenocarcinoma tissues might refine the prognostic value of tumor-infiltrating CD8 + lymphocytes. Using multiplex immunohistochemistry-based image analysis on whole-tissue sections of 214 pancreatic ductal adenocarcinomas, we measured CD8 + cell densities in the tumor center, the tumor margin, and the whole tumor, along with the proximity of CD8 + cells to carcinoma cells. Multivariable Cox regression analysis was performed to assess the associations of CD8 + cell densities with pancreatic cancer-specific survival, adjusting for clinicopathologic and immune-related features, including tumor expressions of TP53, SMAD4, and the programmed cell death 1 ligand 1 (CD274, PD-L1) and the extent of tertiary lymphoid structures. There was substantial heterogeneity in CD8 + cell density, with the mean density in the tumor center less than half that in the tumor margin. Tumor CD274 expression and extensive tertiary lymphoid structures were appeared to be associated with higher CD8 + cell density in the tumor margin (P = 0.037 and P = 0.005, respectively), but not with that in the tumor center (P > 0.50). The association of higher CD8 + cell density with prolonged survival was significant for the whole tumor (P trend  = 0.009); however, the association was stronger for the tumor center (P trend  = 0.002) and insignificant for the tumor margin (P trend  = 0.07). Tumor cell-CD8 + cell distance correlated strongly with CD8 + cell density, whereas the density of CD8 + cells proximate to cancer cells exhibited no prognostic association. In conclusion, spatial computational analysis on pancreatic ductal adenocarcinoma reveals the prognostic validity of CD8 + cell density in the tumor center, where CD8 + cell infiltration is ununiformly restricted, likely suggesting pro-tumorigenic roles of the immunosuppressive tumor microenvironment of pancreatic cancer.

Background: We aimed to evaluate the efficacy and safety of 5-fluorouracil-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC)., Methods: This retrospective study investigated the clinicopathological features and > 5-year survival of patients with T3/T4 PDAC who underwent NACRT at our institute between 2003 and 2012., Results: Seventeen resectable and eight borderline resectable patients were included. The protocol treatment completion and resection rates were 92.0% and 68.0%, respectively. Two patients failed to complete chemotherapy owing to cholangitis or anorexia. Common grade 3 toxicities included anorexia (12%), neutropenia (4%), thrombocytopenia (4%), anemia (4%), and leukopenia (12%). Pathologically negative margins were achieved in 94.1% of patients who underwent pancreatectomy. Pathological response according to Evans' classification was grade IIA in 10 patients (58.8%), IIB in 5 patients (29.4%), and IV in 2 patients (11.8%). Postoperative pancreatic fistulas were observed in four patients (23.5%), delayed gastric emptying in one patient (5.9%), and other operative morbidities in four patients (23.5%). The 1-, 2-, 5-, and 10-year overall survival rates were 73.9%, 60.9%, 60.9%, and 39.1%, respectively (median follow-up period, 80.3 months)., Conclusions: NACRT is tolerable and beneficial for resectable/borderline resectable PDAC, even in the long-term.

Background: /Objectives: The objectives of this study were to identify the factors affecting patients' survival and the characteristics of five-year survivors of pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy as well as to clarify the correlation between the development of postoperative complications and a five-year survival., Methods: A total of 104 patients underwent pancreatectomy for PDAC between April 2005 and March 2013 with curative intent. Patients who survived for more than five years after pancreatectomy were classified as long-term survivors. Sixteen demographic and clinical variables and 10 pathological variables were comprehensively assessed for their associations with the patients' survival time and long-term survival., Results: The presence of preoperative comorbidity (OR: 1.65, 95% CI 1.02-2.67, p = 0.042), postoperative overall complications (OR: 1.78, 95% CI 1.03-3.10, p = 0.041), a lymph node positivity ratio of ≥0.2 (OR: 3.04, 95% CI 1.51-6.11, p = 0.002), and portal invasion (OR: 2.58, 95% CI 1.48-4.49, p = 0.001) were identified as independent factors affecting the patients' survival. The absence of postoperative overall complications was identified as an independent factor related to long-term survival in the multivariate analysis (OR: 0.08, 95% CI 0.01-0.82, p = 0.034)., Conclusions: The presence of preoperative comorbidity, postoperative overall complications, LNR ≥0.2, and portal invasion were prognostic factors affecting the patients' survival, and avoiding postoperative complications after pancreatectomy might contribute to the long-term survival of PDAC patients after pancreatectomy. The further improvement of surgical procedures and perioperative care in order to reduce the rate of postoperative complications should be attempted., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

A 74-year-old man was admitted for evaluation of a pancreatic tumor. Abdominal CT revealed a multilocular cystic tumor with thickened septal walls and an enhanced mural nodule in the head of the pancreas, as well as enlarged para-aortic lymph nodes. FDG-PET revealed FDG accumulation in the nodule and in the para-aortic nodes. The tumor was diagnosed as intraductal papillary mucinous carcinoma (IPMC) with para-aortic lymph node metastases. After 2 courses of chemotherapy with gemcitabine and nab-paclitaxel, the tumor decreased slightly in size, but the lymph nodes did not change. Surgery was then performed. Intraoperative pathology examination confirmed that the para-aortic lymph nodes had only inflammatory swelling. Accordingly, pylorus-preserving pancreaticoduodenectomy was performed. Histopathology examination revealed atypical cells without invasion, and IPMC (TisN0M0;stage 0) was diagnosed. It is thus important for selection of the appropriate treatment approach to determine if enlarged para-aortic lymph nodes are benign or malignant.

Background: Postoperative pancreatic fistula (POPF) is a major complication of distal pancreatectomy (DP). Several procedures for resection and closure of the pancreas have been proposed; however, the rate of POPF remains high. The aims of this study were to investigate the relationship between perioperative factors and POPF and to clarify the advantages of pre-firing compression of the pancreas in the DP., Patients and Method: From 2008 to 2016, records of 75 patients who underwent DP were retrospectively reviewed. The relationship between the perioperative factors and clinically relevant POPF was investigated., Results: Univariate analysis showed that body mass index, thickness of the pancreas, and pre-firing compression were significantly related with clinically relevant POPF. Multivariate analysis showed that the pre-firing compression was an independent factor of clinically relevant POPF (OR = 44.31, 95%CI = 3.394-578.3, P = 0.004)., Conclusions: Pre-firing compression of the pancreas can prevent clinically relevant POPF in DP., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery., Methods: Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA., Results: Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival., Conclusions: Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response.

Background: Although autoantibodies to cancer antigens are candidates for biomarkers, no comprehensive studies to detect cancer-specific antibodies have been performed. This study identified autoantibodies in the sera of pancreatic cancer (PC) patients using proteomics based on a wheat germ cell-free protein production system., Methods: We constructed a biotinylated protein library of 2,183 genes. Interactions between biotinylated proteins and serum antibodies were detected by AlphaScreen® assay. Relative luminescence signals of each protein in 37 PC patients and 20 healthy controls were measured, and their sensitivity and specificity for PC were calculated., Results: Luminescence signals of nine proteins were significantly higher than those of healthy controls, with calcium and integrin binding 1 (CIB1) protein showing the greatest significance (p = 0.002). Sensitivity, specificity, positive predictive value and negative predictive value of CIB1 autoantibody alone for PC were 76, 70, 82, and 61 %, respectively, and 97, 35, 74, and 88 %, respectively, when the four most significant proteins were combined. Presence of these autoantibodies did not vary significantly with other clinicopathological characteristics., Conclusion: Several autoantibodies, including CIB1, are potential biomarkers for PC.

Background/purpose: Although pancreatic cancer produces upstream obstructive pancreatitis, acute pancreatitis is a less common manifestation of pancreatic cancer. This study aimed to clarify the subgroup of pancreatic cancer patients who present with an episode of acute pancreatitis (Group I) in comparison with a matched group of pancreatic cancer patients without pancreatitis (Group II) and another group of acute pancreatitis patients without pancreatic cancer (Group III)., Methods: This was a retrospective comparative study of 18 patients in Group I, 300 patients in Group II and 141 patients in Group III., Results: The mean age of Group I was 63.7 years and the male to female ration was 1:0.3. Serum CA 19-9 levels were elevated in 80 %. The main pancreatic duct was incompletely obstructed in 7 patients. There were no significant differences in location of tumor, clinical stage, resection rate and survival months between Group I and II. Acute pancreatitis secondary to pancreatic cancer was more likely to be mild (94 vs. 72 %,p < 0.05) and relapsed (39 vs. 16 %,p < 0.05) compared with Group III., Conclusions: Anatomic evaluation of the pancreas should be performed in patients with acute pancreatitis with no obvious etiology, even if the pancreatitis is mild, to search for underlying malignancy., (© 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/aims: Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates., Methods: Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant., Results: Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN., Conclusions: In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer., Methods: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined., Results: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts., Conclusion: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.

Proteinase-activated receptor-2 (PAR-2), which is a G protein-coupled receptor, is activated in inflammatory processes and cell proliferation. We previously demonstrated that an anti-PAR-2 antibody suppresses proliferation of human pancreatic cells in vitro. However, there have been no studies of PAR-2 signaling pathways in vivo. The aim of this study was to determine whether blockade of PAR-2 by RNA interference influences pancreatic tumor growth. We originally constructed small interfering RNAs (siRNAs) targeting human PAR-2, and performed cell proliferation assays of Panc1 human pancreatic cancer cell line with these siRNAs. Intratumoral treatment with these PAR-2 siRNAs and atelocollagen was also performed in a xenograft model with nude mice and Panc1 cells. siRNAs against human PAR-2 inhibited proliferation of Panc1 cells, whereas control scramble siRNAs had no effect on proliferation. The PAR-2 siRNAs dramatically suppressed tumor growth in the xenograft model. PAR-2-specific siRNA inhibited growth of human pancreatic cancer cells both in vitro and in vivo. Blockade of PAR-2 signaling by siRNA may be a novel strategy to treat pancreatic cancer., ((c) 2007 Wiley-Liss, Inc.)

A solid pseudopapillary tumor (SPT) of the pancreas is a rare type of pancreatic neoplasm found predominantly in young women. SPTs typically behave as though benign; however, in some cases they also have malignant potential. We encountered a rare case of a recurrent SPT that developed 4 years after the initial surgery in an elderly male patient. Abdominal computed tomography (CT) revealed that the 61-year-old patient had four intra-abdominal masses, suggesting a recurrence of SPT. The patient had a history of distal pancreatectomy due to SPT in the pancreatic tail 4 years previously. These tumors showed positive signals on diffusion-weighted magnetic resonance imaging (MRI), and were treated successfully by aggressive surgical resection. Microscopic diagnosis was compatible with recurrent tumors of SPT. A chemosensitivity test, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST), showed that the resected tumors were sensitive to several antitumor drugs. We suggest that the CD-DST may be used to indicate promising antitumor agents for treating SPTs with malignant tendencies. In addition, a diffusion-weighted MRI can be useful for accurately visualizing SPTs of the pancreas.

Our experience of arterial infusion chemotherapy combined with regional hyperthermia in the treatment of non-resectable pancreatic cancer was presented. A patient with cancer in the pancreatic head with accompanying extensive metastasis in both hepatic lobes was treated by sub selective aortic infusion of 5-FU and MMC with microwave hyperthermia. Both the cancer in the pancreatic head and the liver metastasis showed complete remission for 16 years.

Fourty eight patients with cancer of head of pancreas have been treated by the intra-arterial infusion of 5-FU and Mitomycin C alone or in combination with regional hyperthermia, employing microwave machine operating at a frequency of 2450 MHz. In patients treated with intra-arterial infusion chemotherapy alone the average survival of 4.2 month was attained, whereas the average survival of 9.0 month has been seen in 39 patients treated with infusion chemotherapy and hyperthermia. The hyperthermia treatment has improved the local therapeutic effects and the effects on the survival of the patients. Thanks to this combination therapy 27 of 39 patients (69%) survived more than 6 month, and 12 patients (31%) survived more than one year, longest survival being 7 years. This study confirms that heat administered by the microwave unit potentiated the effects of the intraarterial infusion chemotherapy.

The incidence of pancreatic cancer has increased recently. The average age of pancreatic cancer patients in our series was 60.6 years; the male to female ratio was 2.3:1. As for tumor location, the head (45.5%) was the most frequent followed by the body (32.7%) and the tail (20%). Pancreatic cancers were histologically classified as duct carcinoma (88.2%), acinar cell carcinoma (0.9%), islet cell carcinoma (1.8%) and undifferentiated carcinoma (9.1%). In 17 cases (15.5%), diabetes mellitus was an accompanying complication.