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Background The prognosis of patients with borderline resectable pancreatic cancer with arterial contact (BRPC-A) is extremely poor, and effective preoperative treatment is indispensable. We evaluated the clinical efficacy and safety of neoadjuvant chemotherapy, including gemcitabine, nab-paclitaxel and S-1 (GAS), for patients with BRPC-A. Material and methods A multicentre, single-arm, phase II study was performed. Patients were administered 1000 mg/m2 gemcitabine on day 1, 125 mg/m2 nab-paclitaxel on day 1 and 60–100 mg/day S-1 on days 1–7 during a 14-day cycle. Patients were then assessed for resectability and response to treatment after six cycles. The primary end-points were 2-year overall survival (OS) rate and median OS time (trial registration: jRCTs061180045, UMIN000016630). Results Forty-seven patients with BRPC-A were eligible for the present study. Six courses of neoadjuvant GAS regimen were completed in all eligible patients. The rate of grade III/IV toxicities occurred in 14 (30%) patients during the neoadjuvant GAS regimen. The response and disease control rates were 43% and 96%, respectively. Forty-five (96%) patients received potentially curative pancreatectomy, whereas two did not owing to disease progression. R0 resection was performed in 40 (86%) of 47 eligible patients. Eleven (24%) patients experienced postoperative major complications (>grade III), including one mortality. The 2-year OS rate and median OS time among 47 eligible patients were 70.1% and 41.0 months, respectively. Conclusions The neoadjuvant GAS chemotherapy regimen for BRPC-A showed good efficacy with mild toxicity, resulting in a high R0 resection rate and prolonged survival in patients with BRPC-A.

This study aimed to assess the impact of neoadjuvant therapy (NAT) for borderline resectable or locally advanced pancreatic cancer (BR/LAPC) on the American Joint Commission on Cancer (AJCC) nodal status. The medical records of BR/LAPC patients who underwent surgery with curative intent were retrospectively reviewed. The nodal status was compared between patients who underwent upfront surgery (UFS) and those who received NAT. Moreover, clinicopathological factors and prognostic factors for overall survival were analyzed. In all, 200 patients with BR/LAPC, 78 with UFS, and 122 with NAT were enrolled. The nodal status was significantly lower in patients after NAT than after UFS (p = 0.011). A multivariate analysis of overall survival showed that UFS (hazard ratio (HR) 1.61, p = 0.024) and N2 status (HR 2.69, p

The benefit of surgery for older patients with extrahepatic cholangiocarcinoma (EHCC) has not been established and the differences in the general condition of younger vs. older patients remain unclear. Patients who underwent curative surgery for EHCC were divided into two groups according to age: those younger than 75 years old (younger group) and those aged 75 years or older (older group). We analyzed the clinical data of the two groups retrospectively. Among the 116 patients analyzed, 45 (38.8%) were in the older group. Regarding comorbidity, only cardiac disease was significantly more common in the older patients; however, the cardiac function of the two groups was identical. There were no significant differences in the prevalence of kidney and lung disease, but renal function was significantly deteriorated and the incidence of the mixed ventilatory defect was significantly greater in the older group. The overall 5-year survival rates for the younger and older groups were 52.4% vs. 50.4% of all cholangiocarcinoma patients (p = 0.458), 42.4% vs. 51.3% of those with hilar cholangiocarcinoma (p = 0.718), and 69.0% vs. 49.1% of those with distal cholangiocarcinoma (p = 0.534), respectively. Improved survival after surgery can be expected in well-selected older cholangiocarcinoma patients. Comorbidities were not necessarily reflected in organ function, with precise organ function assessment being more important when selecting surgical candidates.

The prognostic value of peritoneal lavage cytology (CY) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. We assessed the prognostic impact of CY status stratified by resectability in PDAC patients treated with surgical resection. Clinical data from 440 patients with PDAC who underwent surgical resection were retrospectively analyzed to examine the association of CY status with clinicopathological factors and survival. Positive CY status (CY+) was found in 30 patients (7%). These patients had significantly worse overall survival in both the resectable (R) (P = 0.002) and borderline resectable (BR) (P < 0.001) groups. The median survival time of CY+ patients in the R and BR groups was 25.6 and 6.7 months, respectively. Multivariate analysis revealed that CY+ was an independent prognostic factor in the BR group (P < 0.001) but not in the R group (P = 0.08). In the R group, CY+ patients who received adjuvant chemotherapy had significantly longer overall survival than those without adjuvant chemotherapy (34.3 vs. 9.8 months, respectively; P < 0.001). The prognosis of CY+ patients in the BR group was extremely poor. In the R group, surgical resection combined with adjuvant chemotherapy may improve the prognosis of CY+ patients.

The clinical importance of peritoneal washing cytology (PWC) for cholangiocarcinoma patients remains unclear. The clinical data of 137 extrahepatic cholangiocarcinoma patients who received PWC and curative surgery were retrospectively analyzed. Among the 137 patients analyzed, five (3.6%) had positive PWC, and 132 (96.4%) had negative PWC. The median survival time in patients with negative PWC was 6.45 years, and the overall 1-, 2-, and 5-year survival rates were 86.5%, 75.3%, and 51.6%, respectively. The median survival time in patients with positive PWC was 2.56 years, and the overall 1-, 2-, and 5-year survival rates were 60.0%, 60.0%, and 40.0%, respectively. A multivariate analysis revealed that positive lymph node metastasis (P

This study aims to investigate the positivity rate of the nerve plexus (NPL) around the common hepatic artery (CHA), as well as the impact of dissecting the NPL-CHA, during surgical resection of pancreatic cancer. Clinicopathological factors, including hematoxylin and eosin (H&E) staining and immunohistochemistry, were compared between the resectable pancreatic cancer (RPC) and borderline resectable PC (BRPC) groups. Moreover, the relationship between the NPL-CHA status and overall survival (OS) was investigated. In this study, 136 eligible patients were divided into the RPC (72) and BRPC (64) groups. In the RPC group, all patients were negative for H&E staining and microinvasion, whereas 13 (20%) and five patients (8%) were positive for H&E staining and microinvasion, respectively, in the BRPC group. The median OS times in the NPL-CHA–positive and –negative groups were 29.8 and 60.2 months, respectively (p = 0.088). The multivariate analysis of OS indicated an elevated initial carbohydrate antigen 19-9, lymph node (LN) metastasis, and lack of adjuvant chemotherapy (AC), which independently predicted poor outcomes. In the BRPC subgroup, contact with the CHA on preoperative computed tomography (CT) was a high-risk factor for NPL-CHA positivity. NPL-CHA positivity was only present in the BRPC group. In the absence of CT evidence of CHA contact, NPL-CHA dissection may not have survival benefits.

The clinical implications of pre- and postoperative KRAS-mutated circulating tumor DNA (ctDNA) present in patients with pancreatic ductal adenocarcinoma (PDAC) have remained an unresolved issue. This study sought to investigate the clinical significance of pre- and postoperative ctDNA analyses and their impact on the prognosis of PDAC patients. Digital droplet polymerase chain reaction detected ctDNA in pre- and postoperative plasma samples prospectively obtained from patients with resectable and borderline-resectable PDAC. Its associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. The patients were sorted according to the presence of pre- and postoperative ctDNA, and its ability to stratify prognosis was evaluated. The study analyzed 97 patients. Both pre- and postoperative ctDNA were detected in 9 patients, and neither was detected in 55 patients. Whereas 15 patients harbored only preoperative ctDNA, 18 patients had only postoperative ctDNA. The multivariate analysis showed that the presence of preoperative ctDNA was associated with poorer OS (P = 0.008) and that postoperative ctDNA was not associated with either RFS or OS. Survival did not differ significantly between the patients with a positive shift in ctDNA status and those without detectable pre- or postoperative ctDNA. For the patients with PDAC, the presence of preoperative ctDNA was significantly associated poor OS, whereas postoperative ctDNA was not associated with poor survival. A positive change in ctDNA did not affect patients’ survival.

Aim and Background TJ-100 is a traditional Japanese medicine that affects inflammation and gastrointestinal motility, and is used as a preventive and treatment for paralytic ileus. This study aims at determining the effect of TJ-100 on the peritoneal levels of IFN-γ/IL-9, cytokines related to ileus, after pancreaticoduodenectomy (PD) in a clinical setting. Methods This was a subsidiary study of the clinical trial investigating the effect of TJ-100 on postoperative bowel function. Ascites was collected from 180 patients using an abdominal drainage tube on postoperative day 1 and 3 after PD (POD 1 or POD 3) and used to measure 27 cytokines. We performed univariate and multivariate analyses using several perioperative variables and administration of TJ-100/placebo to determine the effect of TJ-100 on the levels of IFN-γ and IL-9. Results Peritoneal levels of IL-9 and IFN-γ decreased between POD 1 and 3 (Wilcoxon signed-rank test p

The clinical characteristic differences at the initial recurrence site after resection for pancreatic ductal adenocarcinoma (PDAC) remain unknown. We investigated the clinical characteristics in patients with lung recurrence after surgical resection and evaluated the outcome of resection for isolated lung recurrence.Of 442 consecutive PDAC patients who underwent surgical resection between 2002 and 2018, 229 had recurrence on imaging. Initial recurrence sites were the liver, lung, local, peritoneal, multiple organs, and others. We analyzed the clinicopathologic factors and outcomes, comparing by initial recurrence site, and investigated the outcomes of resection for isolated lung recurrence.Liver recurrences were the most frequent (n = 60, 26%), followed by lung recurrence (n = 48, 21%). The interval from surgery to recurrence was significantly longer in lung recurrence (P = 0.0001). Patients with lung recurrence had significantly longer overall survival after diagnosis (P 0.0001). Patients who underwent surgical resection of lung recurrence had a significantly prolonged overall survival rate after recurrence diagnosis (P = 0.004).Patients with lung recurrence had significantly prolonged survival than those with other recurrence patterns. Resection for isolated lung recurrence represented relatively good prognosis, and possibly may be beneficial in highly-selected patients.

Aim To validate a Japanese version of the Gastrointestinal Quality of Life Index (GIQLI) in patients with symptomatic gallstone disease. Methods We investigated responsiveness, reliability, and convergent validity of the translated GIQLI in patients who underwent elective laparoscopic cholecystectomy. Questionnaire scores were compared with the Gastrointestinal Symptom Rating Scale (GSRS) to verify convergent validity. Results There were 120 patients originally enrolled in the study; three were excluded after their surgery as they no longer met the inclusion criteria. Questionnaires were collected from the remaining 117 patients (100% response rate). At 2 weeks post‐surgery, total GIQLI score increased significantly from pre‐surgery levels, suggesting high responsiveness. Cronbach's alpha ranged from 0.901 to 0.934 for the total score, while a comparison of scores at 2 vs 6 weeks post‐surgery yielded an intraclass correlation coefficient of 0.843; thus, the Japanese version of the questionnaire was reliable. Correlations with GSRS ranged between −0.459 and −0.679, indicating fair to good convergent validity. Conclusion The Japanese GIQLI had high responsiveness and reliability to assess how surgery for symptomatic gallstone disease influenced patient quality of life.

This study aimed to reassess the duration of neoadjuvant therapy (NAT) for patients with borderline resectable pancreatic cancer (BRPC). The medical records of patients with BRPC who received NAT before intended curative resection were retrospectively reviewed. Patient demographics, clinicopathological factors, and prognostic factors for overall survival were analyzed. The serum carbohydrate antigen (CA) 19-9 level was examined monthly during NAT. A total of 118 patients with BRPC were enrolled. The median survival time and 5-year overall survival were 28.0 months and 31%, respectively. Three months after NAT, the CA19-9 levels were normal in 57% of the patients, and 92% underwent resection. Multivariate analysis showed that radiological partial response (hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.26–0.99; p = 0.047); a normal CA19-9 level after NAT (HR, 0.30; 95% CI, 0.22–0.66; p = 0.006); and tumor resection (HR, 0.29; 95% CI, 0.13–0.67; p = 0.005) were independent predictors of better survival. The median CA19-9 level and the rate of normal CA19-9 levels before and after NAT were 256 (interquartile range (IQR), 23–1197) U/mL and 33%, and 27 (IQR, 7–176) U/mL and 57%, respectively. A normal CA19-9 level after NAT was an independent predictor of better survival in patients with BRPC. A longer NAT duration might contribute to improved prognosis of patients with elevated CA19-9 levels.

Introduction: The aim of this study was to identify preoperative risk factors for poor survival in patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with upfront surgery. Methods: Medical records of 268 patients with resectable PDAC defined by resectability status who underwent upfront surgery were reviewed retrospectively. Multivariate analyses were performed to identify preoperative risk factors for recurrence-free survival (RFS) and overall survival (OS). Moreover, a binary logistic regression model was built to determine preoperative independent risk factors of 2- and 3-year recurrence and survival. Results: Multivariate analyses identified CA19-9 (≥100 U/mL, p < 0.001) as an independent risk factor for poor RFS, and worse performance status (1 or 2, p = 0.03), platelet:lymphocyte ratio (p = 0.04), and preoperative CA19-9 (≥100 U/mL, p < 0.001) as independent risk factors for poor OS. Moreover, preoperative CA19-9 (≥100 U/mL) was the only independent risk factor identified for 2- and 3-year recurrence and survival. Discussion/Conclusion: Preoperative CA19-9 (≥100 U/mL) was the most reliable preoperative predictive factor for poor survival in resectable PDAC treated with upfront surgery. These findings warrant further clinical trials investigating efficacy of neoadjuvant therapy targeting the subset of patients with resectable PDAC who have elevated preoperative CA19-9, namely, those with high risk of poor prognosis.

Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

The survival benefit associated with distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for patients with borderline resectable or locally advanced pancreatic body carcinoma is controversial. The aim of this study was to evaluate the impact of DP-CAR following neoadjuvant chemotherapy on survival in patients with borderline resectable or locally advanced pancreatic body carcinoma.Medical records of patients with pancreatic ductal adenocarcinoma who underwent distal pancreatectomy (DP, n = 102) and DP-CAR following neoadjuvant chemotherapy (n = 32) between 2008 and 2019 were analyzed retrospectively. Short- and long-term outcomes were compared between the two groups.All patients who underwent DP-CAR had tumor contact with the celiac axis. Of these, 30 patients underwent preoperative embolization of the common hepatic artery. The pretreatment tumor size of patients who underwent DP-CAR was larger (P 0.001), and rates of blood transfusion (P = 0.003) and postoperative complications (P = 0.016) were higher in patients who underwent DP-CAR compared with patients who underwent DP. The 5-year survival rate of patients who underwent DP and DP-CAR were 50.6% and 41.1%, respectively (median survival time, 65.9 vs 37.0 months). For all 134 patients, pretreatment serum CA19-9 levels (P 0.001), adjuvant chemotherapy (P 0.001), and lymph node status (P = 0.035) were independent prognostic factors of overall survival by multivariate analysis.DP-CAR following neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic body carcinoma may bring the same survival impact as DP, despite increased morbidity.

The Frey procedure, which involves longitudinal pancreaticojejunostomy with coring-out of the pancreatic head, is considered the ideal surgical procedure for chronic pancreatitis with pancreas head stone. Long-term relief from abdominal pain after the Frey procedure was reported to reach about 90%, and this is the most common surgical procedure for chronic pancreatitis in Japan. However, coring-out has the potential risk of severe complications such as bile duct injury, pancreatic fistula, and postoperative hemorrhage. Therefore, we introduce a new lithotripsy technique using laparoscopic coagulation shear without coring-out.

One of the most severe pancreatic surgery complications is post-pancreatectomy hemorrhage (PPH). This study’s aim was to evaluate the efficacy of flooring the major vessels with falciform ligament in preventing PPH after pancreatoduodenectomy (PD). This study was a retrospective review of 500 consecutive patients who underwent PD between Jan 2010 and Dec 2019 at Hiroshima University. Morbidities, including postoperative pancreatic fistula (POPF) or PPH and 90-day mortality, were analyzed. The study cohort was divided into two groups based on the time of surgery (2010–2016 and 2017–2019), i.e., before and after implementation of falciform ligament flooring method. The patient characteristics, operative parameters, clinicopathological factors, morbidity, and mortality were compared between the two periods. Morbidity and mortality rates in the entire cohort were 21% and 1.4%, respectively. The incidence of Grade B/C POPF and PPH was 9.0% and 3.8%, respectively. There was no significant difference between the two periods with respect to Grade B/C POPF, morbidity rate, and mortality rate; however, the rate of Grade B/C PPH significantly decreased from 5.2 to 1.6% p = .027. On multivariate analysis, the absence of the falciform ligament flooring method was an independent PPH risk factor p = .003. Falciform ligament flooring method may help decrease the incidence of PPH after PD.

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential.To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone).Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed.In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS.High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

The safety and efficacy of reinforced staplers during distal pancreatectomy (DP) remain controversial because of the small sample size. This multicenter single-arm prospective study aims to evaluate the safety and efficacy of reinforced staplers with bioabsorbable material during DP. Between October 2014 and August 2015, 121 patients scheduled for DP were enrolled in this study at 11 institutions in Japan. The primary endpoint was the incidence of clinically relevant pancreatic fistula. Protocol treatment was defined as “distal pancreatectomy using reinforced staplers.” Per-protocol analysis of 105 patients was performed; 16 of the patients were excluded based on discontinuation of protocol treatment criteria. Clinically relevant pancreatic fistula occurred in 13 (12.4%) of 105 patients. The overall morbidity rate was 29.5% (31 of 105 patients) and severe complication (Clavien classification IIIa or more) was 10.5% (11/105). Mortality rate was 0%, although reoperations were performed on two patients (1.9%). Multivariate logistic regression analysis of independent risk factors for clinically relevant pancreatic fistula after DP using reinforced stapler closure was operative time more than 240 min (P = 0.047, odds ratio 5.79), registration numbers less than 10 (P = 0.046, odds ratio 13.01), and staple line hemorrhage (P = 0.003, odds ratio 16.34). This study confirms the safety of reinforced staplers for pancreatic stump closure during DP. However, the efficacy of reinforced staplers for decreasing clinically relevant pancreatic fistula could not be drawn from this study. This prospective study was registered with ClinicalTrials.gov (NCT02270554) and UMIN Clinical Trial Registry (UMIN000015384).

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

Background The frequency and prognosis of resected deficient mismatch repair (dMMR) pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study was designed to assess the frequency of dMMR and its clinicopathological relevance in Japanese patients with PDAC treated with surgical resection. Methods A total of 400 consecutive patients with PDAC who underwent surgical resection at Hiroshima University were enrolled. Immunohistochemical staining with four antibodies including MLH1, MSH2, MSH6, and PMS2 was used to determine the presence of dMMR in PDAC specimens. Statistical analyses were applied to evaluate the frequency and clinical outcomes of these patients. Results Of these 400 patients, five (1.3%) had dMMR (two had MLH1 deficiency, two had PMS2 deficiency, and one had MSH2 deficiency). We found a significantly different histological differentiation pattern between patients with dMMR and those with proficient mismatch repair (pMMR) (P = .03). Univariate survival analysis revealed no significant differences between dMMR and pMMR in recurrence-free survival (P = .268) or overall survival (P = .173). Conclusions The incidence of dMMR in Japanese patients with resected PDAC is low, and we found no ethnic-specific differences when comparing the incidence to that in Caucasian patients. In the current study, no significant difference was found in recurrence-free and overall survival between patients with dMMR and pMMR.

PURPOSE The aim of this study was to assess the validity of surgical resection for patients with pancreatic ductal adenocarcinoma (PDAC) aged ≥80 years stratified by resectability status. METHODS Medical records of 245 patients with resectable (R) and 169 with borderline resectable/unresectable (BR/UR) PDAC were reviewed retrospectively. Of the total of 414 patients, 56 (14%) were ≥80 years. The prognostic impact of age ≥80 years was analyzed with stratification by resectability status. RESULTS No significant difference was found in the incidence of major complications between patients aged ≥80 versus

Although metastasis in lymph nodes along the left side of superior mesenteric artery (SMA-LNs-lt) is sometimes found, survival benefit of SMA-LN-lt dissection for pancreatic head cancer is still unclear. The purpose of this study is to evaluate the prognostic significance of SMA-LN-lt metastasis and micrometastasis. A total of 166 patients with pancreatic head cancer who underwent pancreatectomy with lymphadenectomy including SMA-LNs-lt between 2002 and 2017 were reviewed retrospectively. Micrometastasis was evaluated by immunohistochemistry. Twenty patients (12%) had SMA-LN-lt metastasis detected by hematoxylin and eosin (HE) staining, and eight patients (5%) had micrometastasis. Patients with SMA-LN-lt HE-positive or micrometastasis group experienced significantly shorter overall survival (OS) than those without (p = .015). In multivariate analysis, SMA-LN-lt HE-positive or micrometastasis (p = .034), portal vein resection (p = .002), histologic grade 2/3 (p = .046), LN metastasis (p = .002), and lack of adjuvant chemotherapy (p

Background Although serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC. Methods Pre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available. The relationships of clinicopathological factors, including pre- and postoperative CA19-9, SPan-1, and DUPAN-II levels, with overall survival (OS) were analyzed using univariate and multivariate analyses in 149 patients for whom both pre- and postoperative tumor markers were available. Results Elevated pre-operative CA19-9 (≥37 U/mL), SPan-1 (≥30 U/mL), and DUPAN-II (≥150 U/mL) levels were found in 113 (60%), 96 (51%), and 82 (43%) patients, respectively. In multivariate analysis, absence of adjuvant chemotherapy (hazard ratio [HR], 4.17; p = 0.001), R1 resection (HR, 1.90; p = 0.03), higher histological grade (HR, 1.99; p = 0.02), advanced UICC T factor (HR, N/A; p = 0.04) and elevated postoperative CA19-9 (HR, 3.39; p = 0.009) were identified as independent predictors for worse OS. Conclusion When the prognostic impacts of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC were compared, elevated postoperative CA19-9 was the strongest predictive marker of poor survival in the pre- and post-operative period.

Background/Objectives The loss of skeletal muscle mass (sarcopenia) is associated with the poor prognosis of pancreatic cancer. It has been reported pancreatic exocrine insufficiency (PEI) is associated with serum nutritional markers in chronic pancreatitis. However, there has been no report about the relationship between sarcopenia and PEI. The aim of this study is to determine whether body composition, including skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue content (IMAC), and serum nutritional markers are associated with pancreatic exocrine function in patients with pancreatic disease. Methods Data were collected prospectively on 132 patients with pancreatic disease. SM, SAT, VAT and IMAC were assessed by computed tomography. Patients underwent a 13 C-labeled mixed triglyceride breath test to measure pancreatic exocrine function. Serum nutritional markers were measured at the same time of 13 C-labeled mixed triglyceride breath test. Patients were stratified by quartiles according to each body component, and for each component the lowest group was defined as the lowest quartile, treating men and women separately. The lowest group for SM was defined as sarcopenia. PEI was defined as a percentage 13 CO 2 cumulative dose at 7 h below 5%. Results Sarcopenia was associated with PEI in both men (P Conclusions Sarcopenia is independently associated with PEI in patients with pancreatic disease.

Background: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC. Methods: We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA. Results: Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P

Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI.A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a (13)C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent (13)CO2 cumulative dose at 7 hours (% dose (13)C cum 7 h)5% on the (13)C-labeled mixed triglyceride breath test was considered diagnostic of postoperative PEI. Relationships between postoperative PEI and clinicopathologic factors including remnant pancreatic volume were analyzed.Pancreatoduodenectomy and distal pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose (13)C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P.001). The cut-off value of remnant pancreatic volume for predicting postoperative PEI was 24.1 mL by receiver operating characteristic curve analysis. Multivariate analysis revealed that remnant pancreatic volume24.1 mL was the only independent predictive factor for the development of postoperative PEI in patients who underwent pancreatectomy (P.001, hazard ratio; 5.94, 95% confidence interval; 2.96-12.3).Remnant pancreatic volume is associated closely with postoperative PEI after pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy.

It is still unclear whether micrometastasis of para-aortic lymph nodes (PALNs) in pancreatic ductal adenocarcinoma (PDAC) is tantamount to PALN metastasis detected by hematoxylin and eosin (HE) staining. A total of 242 patients with PDAC who underwent radical pancreatectomy with PALN dissection were eligible for this study. Micrometastasis in PALNs was evaluated by CAM 5.2 immunohistochemistry. The relationship between PALN status and overall survival (OS) was analyzed. Of the 242 enrolled patients, 25 (10 %) had PALN metastasis detected by HE (PALN HE-positive), and 21 (9 %) had PALN micrometastasis not detected by HE but identified by CAM 5.2 immunohistochemistry. Univariate analysis revealed that patients with PALN micrometastasis (p = .004) and PALN HE positivity (p = .003) had a significantly shorter OS than those without PALN metastasis, whereas no significant difference was observed between the two former groups (p = .874). In multivariate analysis, lack of adjuvant chemotherapy (hazard ratio [HR] 2.43, p < .001), PALN micrometastasis (HR 1.89; p = .046), and PALN HE-positivity (HR 1.89, p = .023) were identified as independent risk factors for poor prognosis. Within a subset of 46 patients with PALN HE-positivity or micrometastasis, lack of adjuvant chemotherapy was independently associated with poor OS (HR 2.58. p = .029). The prognosis of patients with PALN micrometastasis was extremely poor as well as HE-positive PALNs. However, postoperative adjuvant chemotherapy may contribute to improving the prognosis of PDAC patients with PALN metastasis.

We evaluated the usefulness of the Amplatzer vascular plug (AVP) for preoperative embolization before distal pancreatectomy with en bloc celiac axis resection (DP-CAR). Between April 2010 and September 2017, 19 patients with locally advanced pancreatic body cancer underwent preoperative embolization of the common hepatic and the left gastric artery (CHA, LGA) with AVP or coils. We compared the embolization success rate, embolization-related complications, the time required for preoperative embolization before DP-CAR and the procedure costs in patients whose CHA was AVP- (n = 7) or coil (n = 12) embolized. The success rate for preoperative AVP and coil embolization was 100% and 83.3%, respectively. The median procedure time was shorter in patients whose CHA was embolized with AVP than coils; the difference was not significant (p = 0.045). The total cost was significantly lower for AVP than coil embolization (p = 0.01). The AVP is useful for the preoperative embolization of the CHA before DP-CAR.

Our previous study aimed to examine the effect of TJ-100, a widely used herbal medicine, on intestinal function following pancreaticoduodenectomy (PD) in a multicenter, randomized, double-blinded, placebo-controlled manner (JAPAN-PD study). This concomitant study investigated the effect of TJ-100 on serum cytokine levels in patients who underwent PD. Due to the fact that several clinical variables can affect the absolute values of baseline serum cytokine levels, the ratios of the cytokine levels on postoperative day (POD)3 to those on POD1 were also used for analysis. The present study enrolled 180/224 randomized patients, of whom 91 received TJ-100 and 89 received placebo. As the main findings of the analysis, Wilcoxon signed-rank test revealed no significant difference in the levels of serum cytokines between the groups; however, patients in the TJ-100 group without severe inflammatory complications exhibited significantly higher ratios of interleukin (IL)-4 (n=123), IL-9 (n=72), IL-10 (n=97), PDGF-BB (n=143) and tumor necrosis factor-α (n=135), compared with patients in the Placebo Group (P

Background and Objectives The aim of this study was to evaluate the efficacy of adjuvant gemcitabine plus S-1(GS) chemotherapy for pancreatic carcinoma patients, stratified by the National Comprehensive Cancer Network (NCCN) preoperative resectability definition. Methods A total of 141 consecutive patients with resected pancreatic carcinoma who received adjuvant GS chemotherapy were evaluated retrospectively. According to the NCCN preoperative resectability definition, tumors were divided into resectable tumors (R group), borderline resectable tumors with portal vein contact (BR-PV group), and borderline resectable tumors with arterial contact (BR-A group). Overall survival and prognostic factors were analyzed. Results Overall 1-, 2-, and 5-year survival rates for the 141 patients were 89.6%, 69.9%, and 41.1%, respectively. Overall survival of the R group was significantly better than that of the BR-PV group and the BR-A group (P

Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers. To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival. Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses. High and low nerve growth factor expression was observed in 62 (55 %) and 50 (45 %) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P

Postpancreatectomy hemorrhage is a potentially life-threatening complication. We report herein our experience with a 65-year-old man with locally advanced pancreatic adenocarcinoma who underwent pancreatoduodenectomy with lymphadenectomy following neoadjuvant chemoradiotherapy. On postoperative day 45, he developed massive hematemesis. Angiography revealed active bleeding from the common hepatic artery, and transcatheter coil embolization of that vessel was successfully performed. On postoperative day 64, he again developed massive hematemesis. Angiography revealed active bleeding from the proximal superior mesenteric artery. Immediately after coil embolization of that vessel, bypass grafting between the superior mesenteric artery and the right common iliac artery was performed, using a greater saphenous vein graft. The combination of embolization and bypass grafting is an option for treatment of bleeding from the superior mesenteric artery in an emergent situation.

Background and objectives The aim of this study was to investigate the prognostic impact of postoperative complications after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) stratified by resectability status. Methods Medical records of 226 patients with pancreatic head carcinoma who underwent PD, including 115 with resectable (R) and 111 with borderline resectable/unresectable (BR/UR) PDAC, were reviewed retrospectively. Major complications were defined as grade III or IV based on the Clavien-Dindo classification system. The prognostic impact of major complications on overall survival (OS) was analyzed using univariate and multivariate analyses with stratification by resectability status. Results A multivariate analysis in the BR/UR group identified R1 resection (P = 0.03), T 3/4 stage (P = 0.03), and incidence of major complications (P = 0.03) as independent risk factors for poor survival, whereas major complications did not affect survival in the R group. Initiation of adjuvant gemcitabine plus S-1 chemotherapy occurred significantly less frequently for patients with major complications than for those without major complications in the BR/UR group (P = 0.02). Conclusion A negative prognostic impact of postoperative major complications after PD was observed in patients with BR/UR PDAC, whereas the prognostic impact was unclear in patients with R PDAC.

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p

There are only a few reports concerning long-term exocrine function after pancreaticoduodenectomy (PD), although the number of long-term survivors has increased. We assessed pancreatic exocrine function after PD in 189 patients to identify risk factors for pancreatic exocrine insufficiency. We evaluated patients’ exocrine function by using the 13C-labeled mixed triglyceride breath test, a noninvasive test feasible in outpatient service units. The present study included 99 patients that underwent pancreaticojejunostomy (PJ) at Wakayama Medical University Hospital and 90 patients that underwent pancreaticogastrostomy (PG) at Hiroshima University Hospital, the standard reconstruction techniques during PD at the respective hospitals. We also analyzed long-term morphological changes of remnant pancreas by computed tomography (main pancreatic duct dilation and parenchymal atrophy), nutritional status, and endocrine function. Independent risk factors for exocrine insufficiency after PD include hard pancreas (P = 0.003, odds ratio; 3.157) and PG reconstruction (P = 0.040, odds ratio; 2.321). Breath test results correlated significantly with post-operative morphological changes, nutritional status, and endocrine function. Atrophic changes of the remnant pancreas in the PG group were more severe than those in the PJ group. Furthermore, for patients with a soft pancreas, postoperative body weight changes, prognostic nutritional index, serum total protein levels as well as exocrine test were worse in the PG group, compared with the PJ group. Our results showed that PJ reconstruction might be superior to PG during PD, from the viewpoint of long-term pancreatic exocrine function, although further prospective studies are needed.

Pancreatic fistula (PF) is one of the leading complications after pancreatic resection for pancreatic carcinoma. The aim of this study was to determine whether PF was associated with deterioration of long-term outcomes in patients with pancreatic carcinoma after surgical resection. Medical records of 210 patients with pancreatic carcinoma who underwent tumor resection were reviewed retrospectively. PF was defined as grade B or C PF according to the criteria of the International Study Group on Pancreatic Fistula. Clinicopathological factors including overall survival were compared between patients with and without PF by univariate and multivariate analyses. Thirty-one patients (15 %) developed postoperative PF, and 179 (85 %) did not. The 31 cases of PF consisted of 27 grade B PF and 4 grade C PF. There were no differences in the use of adjuvant chemotherapy, tumor differentiation, lymph node status, surgical margin status, or UICC stage between groups. Overall 5-year survival rates for patients with and without PF were 25 and 27 %, respectively. There was no significant difference in overall survival between the two groups (P = 0.743). Multivariate analysis demonstrated that the use of postoperative adjuvant chemotherapy (P

Background and Objectives: The aim of this study was to determine the impact of preoperative biliary drainage (PBD) on long‐term survival in patients with pancreatic head carcinoma after surgical resection. Methods: Medical records of 160 patients with pancreatic head carcinoma who underwent surgical resection were reviewed retrospectively. Clinicopathological parameters including long‐term survival were compared between patients who did and did not undergo PBD. Results: Overall survival of patients who underwent PBD (n¼93) was significantly worse than that of patients who did not (n¼67) by univariate analysis (P¼0.030). However, multivariate analysis revealed that PBD was not an independent prognostic factor for overall survival (P¼0.227). Patients who underwent percutaneous transhepatic biliary drainage (PTBD) had significantly worse survival than patients who underwent endoscopic retrograde biliary drainage (ERBD, P¼0.038) and patients who did not undergo PBD (P¼0.001). The rate of peritoneal recurrence in patientswhounderwentPTBDwassignificantlyhigherthanthatofpatientswhounderwentERBD(P¼0.033)orpatientswhodidnotundergoPBD (P¼0.034). Conclusions: PBD may not affect the long‐term survival of patients with pancreatic head carcinoma if ERBD is used. J. Surg. Oncol. 2015;111:270–276. 2014 Wiley Periodicals, Inc.

Background: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). Methods: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. Results: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P

Although bile contamination caused by preoperative biliary drainage (PBD) is a risk factor for infectious complications after pancreatoduodenectomy, the appropriate perioperative antibiotic regimen remains unclear. We evaluated a perioperative antibiotic strategy targeting bile contamination associated with PBD procedures for preventing abdominal infectious complications after pancreatoduodenectomy. Consecutive patients (n = 254) underwent pancreatoduodenectomy at a single center. Perioperative antibiotics were mainly cefazolin in non-PBD cases (n = 116) and cefozopran in internal-PBD cases (n = 87). They were based on preoperative bile cultures in 51 of the external-PBD cases. Intraoperative bile cultures were examined prospectively. Morbidity and abdominal infectious complication rates were evaluated. The incidence of positive intraoperative bile cultures was significantly higher in the internal-PBD (85 %) and external-PBD (90 %) cases than in the non-PBD cases (26 %) (p

Background In recent years, nonalcoholic fatty liver disease (NAFLD) after pancreatoduodenectomy (PD) has become increasingly problematic. Our aims were to clarify the relationship between NAFLD and postoperative pancreatic exocrine function and to identify the risk factors for NAFLD after PD. Methods Patients who underwent PD (n = 104) were assessed with abdominal unenhanced computed tomography (CT) to determine the fatty liver changes and were given a 13C-labeled mixed triglyceride breath test to measure pancreatic exocrine function. The percent 13CO2 cumulative dose at 7 hr (% dose 13C cum 7 hr)