Akio Saiura

Background and Objectives: The clinical significance of lung metastases regarded as subcentimeter pulmonary nodules (SPN) before hepatectomy for colorectal liver metastases (CLM) has not been assessed well.Methods: The data from 569 patients undergoing hepatectomy for CLM from 2010 to 2016 were reviewed. The presence and final diagnosis of SPN were analyzed for their association with overall survival (OS).Results: A total of 143 patients had SPN (25.1%). SPN were proved to be lung metastases in 43 patients (30.1%). Before hepatectomy, lung metastases were suspected in 25 patients (sensitivity: 58%; specificity: 100%). The 5‐year OS of patients with lung metastases (45.4%) was worse than that of those with no pulmonary nodules (60.9%, P = .003). There was no significant difference in the 5‐year OS between the patients with lung metastases diagnosed after hepatectomy (48.7%) and before hepatectomy (41.2%, P = .432). The 5‐year OS of patients who underwent surgery for lung metastases after hepatectomy (60.5%) was similar to that of those with no pulmonary nodules and benign pulmonary nodules (60.9%, P = .6310; 44.0%, P = .899).Conclusion: Although diagnostic sensitivity for SPN before hepatectomy is low, timing of diagnosis does not affect OS. Conclusive lung resection offers OS similar to that of patients without lung metastases.

Background Pancreatoduodenectomy (PD) with portal vein resection (PVR) is a standard operation for pancreatic ductal adenocarcinoma (PDAC) with portal vein (PV) invasion, but positive margin rates remain high. It was hypothesized that regional pancreatoduodenectomy (RPD), in which soft tissue around the PV is resected en bloc, could enhance oncological clearance and survival. Methods This retrospective study included consecutive patients who underwent PD with PVR between January 2005 and December 2016 in a single high‐volume centre. In standard PD (SPD) with PVR, the PV was skeletonized and the surrounding soft tissue dissected. In RPD, the retropancreatic segment of the PV was resected en bloc with its surrounding soft tissue. The extent of lymphadenectomy was similar between the procedures. Results A total of 268 patients were included (177 SPD, 91 RPD). Tumours were more often resectable in patients undergoing SPD (60·5 per cent versus 38 per cent in those having RPD; P = 0·014), and consequently they received neoadjuvant therapy less often (7·9 versus 25 per cent respectively; P < 0·001). R0 resection was achieved in 73 patients (80 per cent) in the RPD group, compared with 117 (66·1 per cent) of those in the SPD group (P = 0·016), although perioperative outcomes were comparable between the groups. Median recurrence‐free (RFS) and overall (OS) survival were 17 and 32 months respectively in patients who had RPD, compared with 11 and 21 months in those who had SPD (RFS: P = 0·003; OS: P = 0·004). Conclusion RPD is as safe and feasible as SPD, and may increase the survival of patients with PDAC with PV invasion.

The administration of exogenous factor XIII (FXIII) is reportedly effective for fistula closure in patients with a low plasma FXIII level. This study was performed to analyze the effect of early administration of exogenous FXIII on postoperative pancreatic fistula (POPF).

Postoperative pancreatic fistula (PF) is the main cause of operative mortality in patients who undergo pancreatoduodenectomy. Various pancreatoenteric anastomosis techniques have been reported to minimize the postoperative PF rate. However, the optimal method remains unknown. This study was performed to clarify the impact of pancreatojejunostomy on clinically relevant PF (CR-PF) between Blumgart anastomosis and Kakita anastomosis in patients with a soft pancreas. In total, 620 consecutive patients underwent pancreatoduodenectomy at our institute from January 2010 to December 2016, and 282 patients with a soft pancreas were analyzed (Blumgart anastomosis, n = 110; Kakita anastomosis, n = 176). Short-term outcomes were assessed, and univariate and multivariate analyses of several clinicopathological variables were performed to analyze factors affecting the incidence of CR-PF. The CR-PF rate was 42.7% (122/286). The CR-PF rate was not significantly different between the Blumgart and Kakita groups (42.7% and 42.6%, respectively; p = 0.985). The morbidity rate (Clavien–Dindo grade ≥ IIIa) was 24.5% (70/286), and the operation-related mortality rate was 0.7% (2/286). In the multivariate analysis, male sex (p = 0.0245) and a body mass index of ≥22 kg/m2 (p < 0.0001) were statistically significant risk factors for CR-PF. The CR-PF rate was not significantly different between patients treated with Kakita versus Blumgart anastomosis.

The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08–2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52–3.85; P < 0.001). In patients with CDX2-low CRC, both DFS and OS were similar between the with and without pre- or post-operative chemotherapy groups (median DFS: 243 versus 247 days; P = 0.73, median OS: 1016 versus 1363 days; P = 0.69). Reduced expression of CDX2 indicates poor DFS and OS, however, it might not represent chemosensitivity in patients undergoing curative liver metastasectomy. (339/350).

B7-H3 (CD276), a member of the family of immune modulators, orchestrates antitumor immunity. To date, only small-sized studies have examined the association of B7-H3 expression with survival in pancreatic cancer, yielding inconclusive results. We evaluated tumor B7-H3 expression in 150 consecutive patients with pancreatic ductal adenocarcinoma using immunohistochemistry. B7-H3 expression was positive (≥10% tumor cells) in 99 of 150 (66%) cases of pancreatic cancer. We classified the tumors into four groups depending on B7-H3 expression (negative, low, intermediate, and high) and found that higher B7-H3 expression was independently associated with lower disease-free survival (DFS; for high vs. negative B7-H3 expression: multivariable hazard ratio (HR) = 3.12; 95% confidence interval (CI) = 1.48–6.15; P_trend = 0.0026). Furthermore, the association of B7-H3 expression with survival differed according to the pathological stage (p-stage) (P_interaction = 0.048, between p-stages I–II and III–IV). The association of B7-H3 positivity with lower DFS was stronger in tumors with p-stage I–II (multivariable HR = 3.10, 95% CI = 1.75–5.69; P < 0.0001) than in those with p-stage III–IV (multivariable HR = 1.20, 95% CI = 0.67–2.28; P = 0.55). We demonstrated that tumor high B7-H3 expression is independently associated with poor survival in patients with pancreatic cancer and that this association is stronger in tumors with p-stage I–II than in those with p-stage III–IV. B7-H3 expression may be a useful prognostic biomarker for identifying aggressive early-stage pancreatic cancer.