Tsutomu Fujii

Developing better practices at the institutional level leads to better outcomes after pancreaticoduodenectomy in 3,378 patients: domestic audit of the Japanese Society of Pancreatic Surgery

The aim of the present study was to assess recent trends in pancreaticoduodenectomy (PD) and the role of institutional standardization on the development of postoperative complications in 3,378 patients who underwent PD in Japan.

Splenic vein resection together with the pancreatic parenchyma versus separated resection after isolation of the parenchyma during distal pancreatectomy (COSMOS-DP trial): Study protocol for a randomised controlled trial

BackgroundIn distal pancreatectomy (DP), it is customary to ligate and divide the splenic vein after isolating it from the pancreatic parenchyma. This is considered essential to prevent disruption of the stump of the splenic vein and consequent intra-abdominal haemorrhage in the event of pancreatic fistula (PF). However, this procedure can be technically demanding, especially when the vein is firmly embedded in the pancreatic parenchyma. The objective of the COSMOS-DP trial is to confirm the non-inferiority of resection of the splenic vein embedded in the pancreatic parenchyma compared with the conventional technique of isolating the splenic vein before resection during DP using a mechanical stapler.MethodsPatients with diseases of the pancreatic body and tail whose pancreatic parenchyma and splenic vein can be divided concurrently during open or laparoscopic DP are considered eligible for inclusion. This study is designed as a multicentre prospective randomised phase III trial. Eligible patients will be centrally randomised to either Arm A (resection of the splenic vein after isolation from the pancreatic parenchyma) or Arm B (co-resection of the vein together with the pancreas). This study aims to establish the non-inferiority of the safety of Arm B compared with that of Arm A; the primary endpoint is the incidence of PF (ISGPF grade B/C).DiscussionThe COSMOS-DP trial will establish the safety of this procedure, such that it can be recommended with more confidence. The use of this procedure will likely result in significant reductions in operative time and blood loss during DP.Trial registrationClinicalTrials.gov, NCT02871804. Registered on 27 July 2016.

Resection for recurrent pancreatic cancer in the remnant pancreas after pancreatectomy is clinically promising: Results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery

Background A therapeutic strategy has not been established for recurrent pancreatic cancer in the remnant pancreas. The purpose of this multicenter survey was to clarify the clinical features of remnant pancreatic cancer and to assess the appropriate operative indications. Methods Clinical data from 114 patients with remnant pancreatic cancer after initial pancreatectomy were collected retrospectively. Clinicopathologic factors and overall survival curves were analyzed, and multivariate Cox proportional hazard models were evaluated. Results Variate analysis revealed that age (≥65 years), body mass index (<20 kg/m2), tumor size (≥20 mm), distance from the pancreatic stump (<10 mm), and resection of the remnant pancreatic cancer were significant prognostic factors. The median survival times of the resected (n = 90) and the nonresected group (n = 24) were 26 and 14 months, respectively (hazard ratio: 0.56; P = .012). When the patients were classified based on recurrence patterns after a second pancreatectomy, the median survival times were 30.5 months in the no recurrence group, 32.0 in the local recurrence group, and 23.0 in the distant metastasis group. A total of 8.9% of the patients had a postoperative complication of Clavien‐Dindo classification III or higher, and the 90‐day mortality rate was 1.1%. Conclusion Resection of the remnant pancreatic cancer could offer a favorable outcome and a chance for a cure. In particular, a young and healthy patient with a relatively small tumor at least 10 mm away from the pancreatic stump appears to be the best candidate for reoperation. Furthermore, the safety profile of resection is acceptable.

Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer

Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A significant correlation between LOXL2 expression and the EMT status defined based on the expression of E-cadherin and vimentin was observed in surgical specimens (P < 0.01). The disease-free survival and overall survival rates among patients with low LOXL2 expression were significantly better than those among patients with high LOXL2 expression (P < 0.001). According to the multivariate analysis, high LOXL2 expression (P = 0.03) was a significant independent prognostic factor for patients with PC. Additionally, LOX inhibition significantly decreased PC cell proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression is potentially associated with PC progression, and LOXL2 expression represents a biomarker for predicting the prognosis of patients with PC who have undergone complete resection.

Randomized Phase II Trial of CapOX plus Bevacizumab and CapIRI plus Bevacizumab as First‐Line Treatment for Japanese Patients with Metastatic Colorectal Cancer (CCOG‐1201 Study)

PURPOSE The aim of this randomized, multicenter, noncomparative, phase II trial was to investigate the efficacy and safety of two potential first-line treatments, capecitabine and oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine and irinotecan (CapIRI) plus bevacizumab, in Japanese patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with untreated mCRC were randomly assigned to receive either CapOX plus bevacizumab (CapOX/BEV arm: bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 2,000 mg/m2 on days 1-14, every 3 weeks) or CapIRI plus bevacizumab (CapIRI/BEV arm: bevacizumab 7.5 mg/kg and irinotecan 200 mg/m2 on day 1 and capecitabine 1,600 mg/m2 on days 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS A total of 107 patients were enrolled. The intent-to-treat population comprised 54 patients in the CapOX/BEV arm and 53 patients in the CapIRI/BEV arm. The median follow-up period was 35.5 months. ORR was 56% in the CapOX/BEV arm and 55% in the CapIRI/BEV arm. Median PFS and OS were 12.4 and 26.7 months in the CapOX/BEV arm and 11.5 and 28.7 months in the CapIRI/BEV arm, respectively. The frequencies of hematological and nonhematological adverse events above grade 3 were 13% and 30% in the CapOX/BEV arm and 25% and 23% in the CapIRI/BEV arm, respectively. CONCLUSION CapOX plus bevacizumab and CapIRI plus bevacizumab are equally effective and feasible as the first-line treatments in Japanese patients with mCRC. IMPLICATIONS FOR PRACTICE The CCOG-1201 study was designed to evaluate the efficacy and safety of capecitabine and oxaliplatin plus bevacizumab and capecitabine and irinotecan plus bevacizumab as a first-line treatment in Japanese patients with metastatic colorectal cancer. This article reports on the trial and efforts to define the role of these regimens, including the effect of KRAS status and UGT1A1 polymorphisms in metastatic colorectal cancer.

Spontaneous mesenteric hematoma of the sigmoid colon associated with rivaroxaban: A case report

Highlights • Mesenteric hematoma is a rare condition without specific symptoms.• Rivaroxaban is not affect to the value of PT or APTT.• It is difficult to diagnose mesenteric hematoma.

Clinical Impact of Neoadjuvant Therapy on Nutritional Status in Pancreatic Cancer

BackgroundThe association between neoadjuvant therapy (NAT) and nutritional status in pancreatic cancer (PC) is unknown.ObjectiveThe aim of this study was to assess the impact of NAT on nutritional status.MethodsOverall, 161 patients who underwent pancreatoduodenectomy for PC between August 2010 and March 2017 were enrolled and were divided into two groups: the neoadjuvant group (NAG; n = 67) and the control group (CG; n = 94). Based on relative dose intensity (RDI), patients in the NAG group were further divided into RDI ≥ 80% (n = 39) and RDI < 80% (n = 19). Changes in nutritional index, inflammatory index, and inflammation-based prognostic scores during NAT and the perioperative period were assessed.ResultsRetinol-binding protein, prealbumin, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutrition index significantly worsened in the NAG after NAT (p = 0.007, p = 0.03, p = 0.04, p = 0.007, and p = 0.004, respectively). The recovery of rapid turnover proteins after postoperative day 5 was significantly worse in the NAG compared with the CG (p < 0.05), but tended to be more prompt in the RDI ≥ 80% group among the NAG. There was no significant difference in the incidence of postoperative complications, length of hospital stay, and time to postoperative adjuvant therapy between the NAG and the CG.ConclusionsNAT for PC could aggravate nutritional status and hamper its postoperative recovery. Furthermore, malnutrition might decrease tolerance of NAT. These findings suggest the importance of nutritional support for patients with NAT in PC.

Dual-center randomized clinical trial exploring the optimal duration of antimicrobial prophylaxis in patients undergoing pancreaticoduodenectomy following biliary drainage

The aim of this dual‐center randomized controlled trial was to determine the optimal duration of antimicrobial prophylaxis in patients treated with pancreaticoduodenectomy (PD) who underwent preoperative biliary drainage (PBD) but were without cholangitis.

The efficacy of steroids for postoperative persistent inflammatory reaction in a patient with barium peritonitis: A case report

Highlights • Residual barium in intraperitoneal cavity causes persistent inflammatory reaction.• Steroids are effective for persistent inflammation caused by residual barium.• If infectious or other inflammation origins exist, steroids should be avoided.