Search

A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) has been reported to influence tumor progression and chemosensitivity in human cancers. We assessed the prognostic impact of ADAM12 and its predictive value for neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection.ADAM12 expression was immunohistochemically examined in 428 patients with PDAC who underwent surgical resection. The association of ADAM12 expression with clinicopathological factors and survival was also analyzed.Patients with high ADAM12 expression exhibited significantly shorter median disease-free survival (DFS) (high ADAM12: 17.8 vs. low ADAM12: 37.9 months; P 0.001) and overall survival (OS) (high ADAM12: 33.1 vs. low ADAM12: 65.0 months; P 0.001). A multivariate analysis revealed that high ADAM12 expression was an independent risk factor for poor DFS (P 0.001) and OS (P 0.001) in all eligible patients. Of 100 patients who received neoadjuvant chemotherapy (NAC), high ADAM12 expression was significantly associated with poor DFS in a subset of patients treated with the nab-paclitaxel (PTX) neoadjuvant regimen (P = 0.03), whereas the prognostic value of ADAM12 was not evident in patients not treated with nab-PTX (P = 0.12).A negative prognostic value of high ADAM12 expression was observed in patients with PDAC treated with surgical resection, which was enhanced in patients treated with NAC, including nab-PTX. These results suggested that ADAM12 expression can predict nab-PTX chemosensitivity in PDAC and reflect PDAC progression.

The optimal range of lymph-node dissection for pancreatic tail cancer remains unclear. We investigated the location and frequency of lymph-node metastases to identify the correct range of lymph-node dissection for pancreatic tail cancer.We analyzed clinical data retrospectively, on patients who underwent distal pancreatectomy for resectable left-sided pancreatic cancer, between February, 2006 and March, 2021. Eligible patients were divided into two groups according to the tumor location: those with pancreatic tail cancer (Pt group) and those with pancreatic body or body and tail cancer (non-Pt group).Of the 96 patients analyzed, 61 (64%) were assigned to the Pt group and 35 (36%) were assigned to the non-Pt group. Metastases to stations 7, 8, 9, 10, 11, 14, and 18 were found in 0 (0%), 0 (0%), 0 (0%), 4 (7%), 18 (30%), 2 (4%), and 10 (17%) patients in the Pt group, and in 1 (3%), 4 (12%), 2 (6%), 1 (3%), 18 (51%), 3 (9%), and 6 (17%) patients in the non-Pt group, respectively.Lymph-node dissection at stations 7, 8, and 9 might not be necessary in patients with resectable pancreatic cancer confined to the pancreatic tail.

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.

Preoperative biliary drainage is commonly performed in Japan for patients with cancer of the pancreatic head accompanied by obstructive jaundice due to concerns about liver dysfunction, susceptibility to infection, and hemorrhagic tendency. Therefore, biliary drainage was performed for all patients with preoperative obstructive jaundice in this study. Given the purpose of identifying preoperative risk factors for poor prognosis, separate evaluation of cancers of the pancreatic head versus body/tail might have decreased the statistical power because of the small number of eligible patients. Therefore, we did not separate data based on tumor location in this study. Since examining Lewis antigen status for all patients with pancreatic cancer is impractical, we stratified patients by CA19-9 value without including information about Lewis antigen status. Only 150 (56%) patients were followed for 5 years in this study, so long-term analysis might have had insufficient statistical power. Future studies involving larger numbers of patients with long-term (5 years) follow-up data are required to enhance the results of this study. Since we focused only on preoperative factors in this study, we did not exclude any patients based on information available only after surgery.

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.

An aortic graft-duodenal fistula commonly requires graft replacement and duodenectomy. However, the appropriate surgical approach to the duodenum with aortic graft fistula remains unclear. Herein, we describe the case of an 85-year-old male patient who underwent a pancreas-preserving partial duodenectomy using the mesenteric approach for aortic graft-duodenal fistula. The patient presented with hemorrhagic shock and duodenal bleeding 2 years after undergoing open aortic graft replacement. He first underwent emergent endovascular aortic repair with an artificial vascular graft to achieve hemostasis. Although his general condition stabilized following endovascular treatment, duodenal endoscopy revealed an aortic graft-duodenal fistula, exposing the artificial vascular graft via the third portion of the duodenum. As the radical treatment for aortic graft-duodenal fistula, open graft replacement and pancreas-preserving partial duodenectomy were performed using the mesenteric approach which helps to divide the pancreas and duodenum. The patient recovered without any major complications, such as postoperative pancreatic fistula, and was discharged. In conclusion, the mesenteric approach in partial duodenectomy for aortic graft-duodenal fistula could be safely performed. This procedure is useful to approach the duodenum fixed by fistula formation, which may help reduce intraoperative blood loss, operative time, and surgical invasiveness.

The aim of this study was to assess whether the duration of adjuvant gemcitabine plus S-1 (GS) chemotherapy has any effect on survival in patients with pancreatic ductal adenocarcinoma (PDAC).Of the 290 patients who received adjuvant GS chemotherapy, 100 (34%) received the standard duration (20-29 weeks) and 190 (66%) received an extended duration (≥30 weeks). To reduce selection bias, the prognostic impact (recurrence-free survival [RFS] and overall survival [OS]) based on the duration of adjuvant GS chemotherapy was analyzed using inverse probability of treatment weighting (IPTW). Moreover, to reduce immortal time bias, time-dependent multivariate analyses in which implementation of adjuvant GS chemotherapy was treated as time-varying covariate was also performed.Extended duration of adjuvant GS chemotherapy was significantly correlated with prolonged RFS (P .001) and OS (P .001) after IPTW adjustment. Time-dependent multivariate analyses revealed that extended duration of adjuvant GS chemotherapy was an independent prognostic factor for prolonged RFS (hazard ratio [HR], 0.58, P = .002) and OS (HR, 0.56, P = .005).Extended duration (≥30 weeks) of adjuvant GS chemotherapy in patients with PDAC was associated with an improved prognosis. These findings warrant a further prospective trial on PDAC to investigate the survival benefit of extended adjuvant chemotherapy.

The long-term survival of patients with locally advanced, unresectable pancreatic cancer is extremely poor. We present our experience with a 67-year-old woman who had a 40-mm mass in the body of the pancreas. Tumor infiltration reached the gastroduodenal artery, celiac artery, common hepatic artery, and splenic artery. After 10 courses of FOLFIRINOX, 2 courses of gemcitabine plus nab-paclitaxel, and 6 courses of gemcitabine alone, we performed distal pancreatectomy with celiac axis resection and hepatic artery reconstruction. The bifurcation of the gastroduodenal artery and the proper hepatic artery had to be resected, after which we created 2 anastomoses: proper hepatic-to-middle colic artery, and second jejunal-to-right gastroepiploic artery. Histopathologic examination revealed an Evans grade IIb histologic response to prior treatment and verified the R0 resection status. The patient was discharged on postoperative day 30 after treatment of a grade B pancreatic fistula and is still alive, without recurrence, more than 5 years after initiation of treatment. This patient with locally advanced, unresectable pancreatic cancer achieved long-term survival through perioperative multidisciplinary treatment, including distal pancreatectomy with celiac axis resection and hepatic artery reconstruction. This aggressive procedure could be a treatment option for patients with locally advanced, unresectable pancreatic cancer.

The preoperative risk factors for positive peritoneal lavage cytology (CY) are unknown, especially in patients who received neoadjuvant therapy. In addition, the optimal indications for staging laparoscopy (SL) are still unclear. The aim of this study was to investigate the preoperative risk factors of CY positivity in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection and to determine the optimal indications for SL.We retrospectively analyzed 493 patients with PDAC, including 356 treated with upfront surgery and 137 treated with neoadjuvant chemotherapy (NAC). The preoperative risk factor for CY positivity was investigated along with stratification according to NAC.Among the 493 patients, 36 (7.3%) were CY-positive. The CY-positive frequency in patients who received and did not receive NAC was 9 (6.6%) and 27 (7.6%), respectively. In the multivariate analyses, no independent preoperative predictive factor was found in patients who received NAC, whereas body and tail PDAC were identified as an independent risk factor for CY positivity in patients who did not receive NAC.The preoperative risk factors of CY-positive PDAC are body and tail PDAC in 356 patients who did not receive NAC. However, there is no useful predictive factor for CY positivity in patients treated with NAC. Based on these results, it was difficult to determine the optimal indication for SL especially in NAC cases.

Gastric cancer after pancreaticoduodenectomy was firstly reported in 1995, and the number of reports about this topic has increased in the past years. This review aimed to elucidate the clinicopathological features of this disease.Data for 32 cases were obtained using literature search, and three cases in our institution were added.Twenty cases were reported from Japan, and fifteen cases were from the Western countries (Germany: 1 case, France: 2 cases, USA: 12 cases). In Japanese and the Western cases, the most dominant indication for pancreaticoduodenectomy was distal bile duct cancer and pancreatic ductal adenocarcinoma, respectively. The most frequently applied procedure of pancreaticoduodenectomy was pylorus-preserving pancreatoduodenectomy with pancreaticogastrostomy and pancreaticoduodenectomy with pancreaticojejunostomy, respectively. The median length of time interval from pancreaticoduodenectomy to GC detection tended to be shorter in the Japanese cases (61.5 months vs. 115 months). Of all cases, thirteen (37.1%) patients with gastric cancer showed no abdominal symptoms, and eight were diagnosed at regular gastroscopy. Surgical gastrectomy was performed in 30 patients, and among them, concomitant pancreatectomy was performed in six patients. Four patients received reanastomosis of remnant pancreas using pancreaticojejunostomy. Twenty-two (73.3%) patients had undifferentiated carcinomas, and stage 1, 2, 3, and 4 cancer was identified in 14, six, six, and four patients, respectively. All eight patients who had received routine gastroscopy were T1N0M0 stage 1.Gastric cancers after pancreaticoduodenectomy including newly reported Japanese cases and our institutional cases were reviewed to make Japanese studies available to a broader scientific audience. Further investigation is necessary to elucidate the most important carcinogens among the various potential local and systemic factors.

In recent trend of preoperative chemotherapy, postoperative clostridium difficile infection (CDI) might be increasing in pancreatic ductal adenocarcinoma (PDAC) patients. This study aimed to elucidate the inducement of postoperative CDI in the new era of preoperative chemotherapy.Eligible patients were those who received pancreaticoduodenectomy for PDAC. Patients were classified into two groups according to the presence or absence of postoperative CDI, and the independently associated factors for postoperative CDI were investigated. Additionally, eligible patients were classified using the identified associated factors, and the duration of preoperative antimicrobial administration and incidence of CDI were compared between the groups.Two hundred PDAC patients were eligible for this study, and postoperative CDI was detected in 15 (7.5%) patients. Multivariate analysis revealed that preoperative biliary tract infection (BTI) and chemotherapy (Chemo) were independently associated with postoperative CDI (OR, 4.05; 95% CI, 1.25-13.1; p = 0.0200 and OR, 3.64; 95% CI, 1.14-11.6; p = 0.0209, respectively). The patients were classified into four groups according to the presence or absence of preoperative BTI and Chemo (BTI-/Chemo-, BTI-/Chemo+, BTI+/Chemo- and BTI+/Chemo + group). The median durations of preoperative antimicrobial administration were 0, 2, 8 and 15 days in each group, respectively. Postoperative CDI was detected in 3.7%, 10.0%, 10.5% and 31.3% in each group, respectively, and patients in BTI+/Chemo + group suffered CDI more frequently compared to those in BTI-/Chemo-group (p = 0.00778).Preoperative BTI and chemotherapy might induce postoperative CDI for PDAC patients.

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