Background: The aim of this study was to validate a new definition of borderline resectable pancreatic ductal adenocarcinoma (PDAC) provided by the 2017 international consensus on the basis of three dimensions of anatomical (A), biological (B), and conditional (C) factors, using the data of the patients who had been registered for our institutional protocol of chemoradiotherapy followed by surgery (CRTS) for localized patients with PDAC. Methods: Among 307 consecutive patients pathologically diagnosed with localized PDAC who were enrolled in our CRTS protocol from February 2005 to December 2016, we selected 285 patients who could be re-evaluated after CRT. These 285 patients were classified according to international consensus A definitions as follows: R (resectable; n = 62), BR-PV (borderline resectable, superior mesenteric vein (SMV)/portal vein (PV) involvement alone; n = 27), BR-A (borderline resectable, arterial involvement; n = 50), LA (locally advanced; n = 146). Disease-specific survival (DSS) was analyzed according to A, B (serum CA 19-9 levels and lymph node metastasis diagnosed by computed tomography findings before CRT), and C factors (performance status (PS)) factors. Results: The rates of resection and R0 resection were similar between R (83.9 and 98.0%) and BR-PV (85.2 and 95.5%), but much lower in BR-A (70.0 and 84.8%) and LA (46.6 and 62.5%). DSS evaluated by median survival time (months) showed a similar trend to surgical outcomes: 33.7 in R, 27.3 in BR-PV, 18.9 in BR-A and 19.3 in LA, respectively. DSS in R patients with CA 19-9 levels > 500 U/mL was significantly poorer than in patients with CA 19-9 levels ≤ 500 U/mL, but there were no differences in DSS among BR-PV, BR-A, and LA patients according to CA 19-9 levels. Regarding lymph node metastasis, there was no significant difference in DSS according to each resectability group. DSS in R patients with PS ≥ 2 was significantly worse than in patients with PS 0-1. Conclusions: The international consensus on the definition of BR-PDAC based on three dimensions of A, B, and C is useful and practicable because prognosis of PDAC patients is influenced by anatomical factors as well as biological and conditional factors, which in turn may help to decide treatment strategy.

Background. Circulating apolipoprotein-AII (apoAII-) ATQ/AT is a potential useful biomarker for early stage pancreatic ductal adenocarcinoma (PDAC), but its clinical significance in PDAC patients remains uncertain. The aim of the current study was to assess the usefulness of apoAII-ATQ/AT as a surrogate for the effect of chemoradiotherapy (CRT) and its association with pancreatic exocrine disorder, paying attention to morphological changes of the pancreas. Methods. In the 264 PDAC patients who were enrolled in our CRT protocol, the following parameters were measured at specified time points before and after CRT: serum levels of albumin, total cholesterol, and amylase as indices of pancreatic exocrine function, serum levels of CA19-9, and the pancreatic morphology including tumor size (TS), main pancreatic duct diameter (MPDD), and pancreatic parenchymal volume excluding tumor volume (PPV) by using computed tomography (CT) images. Plasma apoAII-ATQ/AT levels were simultaneously measured with enzyme-linked immunosorbent assay in 4 healthy volunteers and the 44 PDAC patients before and after CRT. Plasma apoAII-ATQ/AT levels after CRT were analyzed according to small/large-MPDD and small/large-PPV groups based on their median values after CRT. Plasma samples after CRT were measured after incubation with human pancreatic juice (PJ) to examine the relevance between apoAII isoforms and circulating pancreatic enzymes. Results. The serum levels of albumin, amylase, CA19-9, TS, MPDD, and PPV after CRT were significantly lower than those before CRT (median, before vs. after: 3.9 g/dl, 74 U/l, 180.2 U/ml, 58.1 mm, 4.0 mm, and 34.8 ml vs. 3.8, 59, 43.5, 55.6, 3.6, and 25.2). ApoAII-ATQ/AT levels (median, μg/ml) of PDAC patients before CRT were significantly lower than those in healthy volunteers: 32.9 vs. 61.2, and unexpectedly those after CRT significantly decreased: 14.7. The reduction rate of apoAII-ATQ/AT was not correlated with those of CA19-9 and TS, indicating that apoAII-ATQ/AT is not a tumor-specific marker. On the other hand, the patient group with large MPDD and small PV exhibited higher apoAII-ATQ levels than those with small MPDD and large PPV. The incubation of plasma samples after CRT with PJ did not alter apoAII-ATQ/AT and apoAII-AT levels but significantly decreased apoAII-ATQ levels, suggesting that circulating pancreatic enzymes markedly influenced apoAII-ATQ levels. Conclusions. ApoAII-ATQ/AT levels are not useful for evaluation of clinical effect of CRT for PDAC, but apoAII isoforms are very useful to assess pancreatic exocrine disorder because pancreatic atrophy and insufficient secretion of circulating pancreatic enzymes are considered likely to influence apoAII-ATQ levels.

We evaluated long-term outcomes including endo- and exocrine functions after pancreaticoduodenectomy (PD) with standardized pancreaticojejunostomy, paying attention to postoperative pancreatic duct dilatation (PDD) and remnant pancreatic volume (RPV), and examined whether postoperative pancreatic fistula (POPF) influenced the configuration of remnant pancreas. We analyzed the records of 187 patients with PD who could have RPV measured by CT volumetry at 1 month after operation and had been followed for more than 6 months. We assessed the risk factors of diabetes mellitus (DM) and PDD, and evaluated association between RPV and pancreatic endo- and exocrine functions assessed by several markers such as albumin, cholesterol, amylase and HbA1c. Regarding RPV, pancreatic exocrine functions were significantly impaired in the small-volume group (SVG: less than 10 ml) than in the large-volume group (LVG: 10 ml or more). The incidence of new-onset or exacerbation of DM did not differ between SVG and LVG. PDD and the primary disease (pancreatic ductal adenocarcinoma compared to bile duct cancer) were selected as the independent risk factors of new-onset or exacerbation of DM by multivariate analysis. Unexpectedly, there was no significant association between POPF and PDD. Early occurrence of POPF after PD did not influence the development of PDD in late period, and long-term follow-up should be made by paying attention to PDD and RPV, because PDD was recognized as the most important risk factor of new-onset or exacerbation of DM and the patients with small RPV suffered from prolonged exocrine dysfunction rather than endocrine dysfunction.

In accordance with previous reports, the incidence of biliary candidiasis (BC) after pancreaticoduodenectomy (PD) was reported to be 0 to 5%, and the clinical significance of BC still has been elusive. In this study, we prospectively evaluated the precise incidence of BC after PD using the CHROMagar Candida plate in an attempt to elucidate whether BC has a significant impact on the clinical outcomes after PD.Patients and Method. From November 2014 to March 2016, the consecutive 51 patients who underwent PD were enrolled for this study. The bile juice was prospectively collected through the biliary stent tube on postoperative days (POD) 3, 7, and 14 and directly incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. In the presence or absence of BC, we compared the incidence of SSIs.Results. The incidence of postoperative BC was 15% on POD 3, 24% on POD 7, and 39% on POD 14, respectively. Taken together, 22 patients out of 51 (43.1%) developed BC after PD. Moreover, the incidence of SSIs was significantly higher in patients with BC than in those without it (71% versus 7%, p=0.005). BC was selected as the only significant risk factor of SSIs after PD among the various risk factors. Even though a cause of BC is unknown, high level of alkaline phosphatase (cut-off line >300 IU/L) was selected as the only preoperative risk factor of the development of BC.Conclusion. We elucidated new evidence in which BC could be the independent cause of SSIs after PD and should not be recognized as just contamination artifacts. Preoperative assessment for identifying carriers of Candida species might be essential for reducing the incidence of SSIs after PD.

Objectives: To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT). Materials and Methods: Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor. Results: OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs 27.5 months, P = 0.014; DSS: 63.3 vs 33.0 months, P = 0.014; RFS: 20.3 vs 11.3 months, P = 0.028). Multivariate analysis identified adjuvant chemotherapy (P = 0.003) as a favorable prognostic factor of OS and tumor budding (P = 0.023) as an adverse prognostic factor of DSS. Conclusions: This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT.