Motokazu Sugimoto

Schematic Pancreatic Configuration: A Risk Assessment for Postoperative Pancreatic Fistula After Pancreaticoduodenectomy

IntroductionPostoperative pancreatic fistula (POPF) remains a serious complication after pancreaticoduodenectomy (PD). Preoperative risk assessment of POPF is desirable in careful preparation for operation. The aim of this study was to assess simple and accurate risk factors for clinically relevant POPF based on a schematic understanding of the pancreatic configuration using preoperative multidetector computed tomography.MethodsThree hundred and eighteen consecutive patients who underwent PD in the National Cancer Center Hospital East between November 2006 and March 2013 were investigated. Pre-, intra-, and postoperative clinicopathological findings as well as pancreatic configuration data were analyzed for the risk of clinically relevant POPF. POPF was defined according to the International Study Group of Pancreatic Fistula classification. POPF grade A occurred in 52 patients (16.4 %), grade B in 84 (26.4 %), and grade C in 6 (1.9 %).ConclusionsIndependent risk factors for POPF grade B/C included main pancreatic duct diameter (MPDd) < 2 mm (P = 0.001), parenchymal thickness ≥ 8 mm (P = 0.018), not performing portal vein/superior mesenteric vein resection (P = 0.004), and amylase level of drainage fluid on postoperative day 3 ≥ 375 IU/L (P < 0.001). Pancreatic configuration data including MPDd and parenchymal thickness were good indicators of clinically relevant POPF.

Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas

BACKGROUND Neural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC. METHODS Participants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC. Immunohistochemical examination of surgical specimens was performed by using CD204 as an M2 macrophage marker, and the area of immunopositive cells was calculated automatically. Prognostic analyses of clinicopathological factors including CD204-positive cells at plx-inv were performed. RESULTS Plx-inv was observed in 91 patients (53.5%). Forty-eight patients showed a high percentage of CD204-positive cell area at plx-inv (plx-inv CD204%(high)). Plx-inv CD204%(high) was an independent predictor of poor outcomes for overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Patients with plx-inv CD204%(high) showed a shorter time to peritoneal dissemination (P<0.001) and locoregonal recurrence (P<0.001). In patients who underwent adjuvant chemotherapy, plx-inv CD204%(high) was correlated with shorter OS (P=0.011) and DFS (P=0.038) in multivariate analysis. CONCLUSIONS Plx-inv CD204%(high) was associated with shortened OS and DFS and early recurrence in the peritoneal cavity and locoregional space. The prognostic value of plx-inv CD204%(high) was also applicable to patients who received adjuvant chemotherapy. High accumulation of M2 macrophages at plx-inv represents an important predictor of poor prognosis.

What is the nature of pancreatic consistency? Assessment of the elastic modulus of the pancreas and comparison with tactile sensation, histology, and occurrence of postoperative pancreatic fistula after pancreaticoduodenectomy

BACKGROUND Although pancreatic consistency is a factor known to have an impact on the occurrence of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), it usually is assessed subjectively by the surgeon. Measurement of the elastic modulus (EM), a parameter characterizing the elasticity of a material, may be one approach for achieving objective and quantitative assessment of pancreatic consistency. This study was conducted to investigate the utility of determining the EM of the pancreas. METHODS Fifty-nine patients who underwent PD and measurement of the EM of the ex vivo pancreas were investigated. Data for EM were compared with the tactile evaluation made by surgeons, histologic findings, and the occurrence of POPF. RESULTS The EM of the pancreas was correlated with the tactile evaluation made by the surgeon (soft pancreas, 1.4 ± 2.1 kPa vs hard pancreas, 4.4 ± 5.1 kPa; P < .001). An EM of >3.0 kPa was correlated with histologic findings including increased ratios of azan-Mallory positivity (P = .003) and α-smooth muscle actin positivity (P = .006), a decreased lobular ratio (P = .021), and an increased vessel density (P < .001). Patients with a pancreatic EM of <3.0 kPa had an increased risk of POPF (hazard ratio, 9.333; P = .002). CONCLUSION Assessment of the EM of the resected pancreas reflects the tactile evaluation made by the surgeon and histological degree of pancreatic fibrosis, and is correlated with the occurrence of POPF after PD.

Assessment of elasticity of colorectal cancer tissue, clinical utility, pathological and phenotypical relevance.

Generally, cancer tissue is palpated as a hard mass. However, the elastic nature of cancer tissue is not well understood. The aim of the present study was to evaluate the clinical utility of measuring the elastic modulus (EM) in colorectal cancer tissue. Using a tactile sensor, we measured the EM of 106 surgically resected colorectal cancer tissues. Data on the EM were compared with clinicopathological findings, including stromal features represented by Azan staining and the α‐SMA positive area ratio of the tumor area. Finally, a cDNA microarray profile of the tumors with high EM were compared with the findings of tumors with low EM. A higher EM in tumors was associated with pathological T, N, and M‐stage tumors (P < 0.001, P = 0.001 and P = 0.011, respectively). Patients with high EM tumors had shorter disease‐free survival than had patients with low EM. The EM showed strongly positive correlation with the Azan staining positive area ratio (r = 0.908) and the α‐SMA positive area ratio (r = 0.921). Finally, the cDNA microarray data of the tumors with high EM revealed a distinct gene expression profile compared with data from those tumors with low EM. The assessment of the elasticity of colorectal cancer tissue may allow a more accurate clinical stage and prognosis estimation. The distinct phenotypical features of the high EM tumors and their strong association with stromal features suggest the existence of a biological mechanism involved in this phenomenon that may contribute to future therapy.

Abdominal skin closure using subcuticular sutures prevents incisional surgical site infection in hepatopancreatobiliary surgery

Background: Hepatopancreatobiliary surgery has a high incidence of postoperative morbidity, including incisional surgical site infection. Although several studies showed that subcuticular sutures reduced incisional surgical site infection in other fields of surgery, their impact on hepatopancreatobiliary surgery remains unknown. The aim of this study was to assess whether subcuticular sutures could reduce incisional surgical site infection in patients undergoing hepatopancreatobiliary surgery. Methods: A total of 436 consecutive patients underwent laparotomy and surgical resection for hepatopancreatobiliary tumors in our department from May 2013 to December 2015. We excluded among them, 8 patients with a follow‐up period <30 days and 1 patient with unclear operative information. The incidence of incisional surgical site infection was compared between use of subcuticular sutures and of stapling, using propensity score analyses. Results: In the baseline cohort (n=427), abdominal skin closure was performed by subcuticular sutures in 245 patients (57.4%) and by stapling in 182 patients (42.6%). The incidence of incisional surgical site infection was 5/245 (2.0%) in the subcuticular suture group and 21/182 (11.5%) in the stapling group (P <. 01). In the propensity score–matched cohort (n=318), patient demographics were well balanced between the two groups, and the incidence of incisional surgical site infection was 3/159 (1.8%) in the subcuticular suture group and 16/159 (10.0%) in the stapling group (P < .01). Propensity score analyses, as well as simple regression analyses, showed subcuticular sutures could consistently reduce incisional surgical site infection (with odd ratios of about 0.20). Conclusion: Use of subcuticular sutures is preferred to stapling for the prevention of incisional surgical site infection in hepatopancreatobiliary surgery.

Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification

We successfully determined the difference of immune microenvironments between pNENs and pancreatic ductal adenocarcinomas (PDACs), and the histology-dependent variability among pNENs using multispectral fluorescent imaging system. Tumour tissue samples including 52 pNENs and 18 PDACs were investigated. The tumour-infiltrating lymphocytes (TILs), their PD-1 and PD-L1 expression in the pNENs were comprehensively and quantitatively analysed and were subsequently compared with those in PDACs. A principal component analysis revealed that the tissue immune profile is related to tumour histology, with distinct groups being observed for NETs, NECs, and PDACs. While NECs and some PDACs had hot immune microenvironments with abundant TILs, NETs had a cold immune microenvironment with few TILs. Moreover, in NETs, the numbers of intraepithelial PD-1high T cells and PD-L1high Type-II macrophages were elevated according to the grade. Univariate analysis revealed that lymph node metastasis, grade, stage, PD-1high T cells, and PD-L1high Type-II macrophages were predictors for recurrence-free survival (RFS), while grade and PD-1high T cells were prognostic factors for overall survival (OS). We also showed that PD-1high T cells and PD-L1high Type-II macrophages were associated with worse outcome in pNENs. Our results support the WHO 2017 tumour classification criteria, which distinguish between G3 NETs and NECs.

The prognostic impact of differentiation at the invasive front of biliary tract cancer

The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Difinv) and tumor budding (Bud) in biliary tract cancer (BTC).

Pancreas-preserving resection of lower biliary tract adenocarcinoma: A coring-out technique

Surgical resection for distal cholangiocarcinoma is usually carried out using pancreaticoduodenectomy (PD). However, because PD is a complex procedure with a high rate of postoperative complications, the surgical indications should be carefully considered, especially for patients with a decreased performance status, significant comorbidities, and/or anatomical anomalies. If curatively carried out, a less invasive, local resection may be an alternative procedure for such patients. In the current study, we present pancreas‐preserving resection of the lower biliary tract in a patient with early‐stage distal cholangiocarcinoma. This procedure was selected to avoid PD with arterial reconstruction because of arterial anomalies. After an abdominal exploration, a cholecystectomy was carried out and the common hepatic duct was transected. The bile duct was dissected from the pancreatic parenchyma without pancreatic resection, downward to the biliopancreatic ductal confluence. Next, a duodenotomy was done opposite Vaters ampulla. The duodenal mucosa around Vaters ampulla was incised and dissected, and the main pancreatic duct (MPD) was divided. The bile duct was completely separated from the pancreatic parenchyma, and the lower biliary tract was totally “cored‐out”. After resection, the MPD was re‐implanted into the duodenal wall, and the duodenotomy was closed. Finally, a Roux‐en‐Y hepaticojejunostomy was created. Postoperative course was uneventful. No tumor recurrence has been observed for 21 months after the operation. Thus, pancreas‐preserving resection of the lower biliary tract appeared to be appropriate for our patient. This organ‐preserving approach can be a useful, alternative procedure in selected patients.