Yuichiro Kato

Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head.

Tumor‐associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumor‐associated macrophages can be affected by cancer‐related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM‐related factors and the clinical impact of TAMs. CD68 (a pan‐macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease‐free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02411.x, 2012)

Clinicopathological Features and Prognostic Factors of Adenocarcinoma of the Esophagogastric Junction According to Siewert Classification: Experiences at a Single Institution in Japan

BackgroundTreatment strategy for adenocarcinoma of the esophagogastric junction (AEG) remains controversial. The aims of this study are to evaluate results of surgery for AEG, to clarify clinicopathological differences according to the Siewert classification, and to define prognostic factors.MethodsWe retrospectively analyzed 179 consecutive patients with Siewert type I, II, and III AEG who underwent curative (R0) resection at the National Cancer Center Hospital East between January 1993 and December 2008.ResultsPatients with AEG were divided according to tumor: 10 type I (5.6%), 107 type II (59.8%), and 62 type III (34.6%). Larger, deeper tumors and nodal metastasis were more common in type III than type II tumors. No significant differences were seen in 5-year survival rates among the three types: type I (51.4%), type II (51.8%), and type III (62.6%). Multivariate analysis showed that depth of tumor and mediastinal lymph node metastasis were independent prognostic indicators. The recurrence rate for patients with mediastinal lymph node metastasis was 87.5%. The risk factors for mediastinal lymph node metastasis were length of esophageal invasion and histopathological grade.ConclusionsMediastinal lymph node metastasis and tumor depth were significant and independent factors for poor prognosis after R0 resection for AEG. Esophageal invasion and histopathological grade were significant and independent factors for mediastinal lymph node metastasis.

Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients

ABSTRACT The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial. Ten vaccinations were performed for 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.

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.

Influence of Excess Body Weight on the Surgical Outcomes of Total Gastrectomy

PurposeWe conducted this retrospective study to identify the influence of excess body weight on the surgical outcome of total gastrectomy (TG) and to evaluate recent advances in this operation.MethodsThe subjects were 644 consecutive gastric cancer patients who underwent TG between 1992 and 2008. Patients with a body mass index (BMI) of 25.0 kg/m2 or greater were defined as overweight (overweight group) and those with a BMI less than 25.0 kg/m2 as not overweight (non-overweight group).ResultsThe operating times were longer (P = 0.005) and intraoperative blood loss was greater (P < 0.001) in the overweight group. The incidence of overall postoperative complications (P = 0.012) and of pancreatic fistula (P < 0.001) were significantly higher in the overweight group. In recent years, we achieved a reduction in operating time (P < 0.001), intraoperative blood loss (P = 0.033), and incidence of pancreatic fistula (P = 0.005), while maintaining curability, in the overweight group.ConclusionsAlthough TG for gastric cancer is technically more difficult in overweight patients, they should not be denied this operation. Conversely, we should make a greater effort to improve the surgical outcomes of overweight patients.

Clinical and histopathological study of "follicular cholangitis": Sclerosing cholangitis with prominent lymphocytic infiltration masquerading as hilar cholangiocarcinoma.

Aim:  Sclerosing cholangitis which mimic hilar biliary carcinoma have not been fully categorized. In this study, we investigated the clinicopathological features of sclerosing cholangitis of unknown origin, so‐called “follicular cholangitis”.

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.

Reactive lymphoid hyperplasia of the liver: literature review and 3 case reports.

Reactive lymphoid hyperplasia (RLH) is a benign non-specific lesion having an unknown etiology and pathogenesis. The lesion is found in various organs but is rare in the liver. We report 3 cases of hepatic RLH associated with an extrahepatic malignant tumor. We also provide a literature review based on a search of the PubMed database from 1983 to 2009. The 3 cases showed radiological findings similar to those for malignant tumors and all cases were misdiagnosed as malignant tumors on the basis of these findings. It is difficult to distinguish RLH from malignant or metastatic tumors on the basis of imaging findings. Hepatic RLH is a rare entity and may cause a false diagnosis of malignancy. Because RLH occurs most commonly in middle-aged females, diagnosis of a hypervascular tumor of the liver requires particular care in these patients, especially if an extrahepatic malignancy is present.

Surgical management for the reduction of postoperative hospital stay following distal pancreatectomy.

BACKGROUND/AIMS Pancreatic fistula remains a major cause of postoperative morbidity in patients undergoing pancreatectomy and is generally difficult to cure. None of the several surgical techniques and devices available for managing pancreatic remnant have been clinically evaluated. METHODOLOGY We retrospectively reviewed medical records of 120 consecutive patients who underwent distal pancreatectomy at our institution between October 1992 and September 2009. Furthermore, we divided these cases into 3 periods based on 2 points at which we changed our surgical strategy. One was September 2004, when we introduced a stapling technique for managing remnant pancreas. The other was November 2006, when we started using a closed active drain. We evaluated the incidence of pancreatic fistula, risk factors for its development, and our strategy in the perioperative period. RESULTS The overall and clinical pancreatic fistula rates gradually decreased but were not significant. The persistent drainage period gradually reduced from 19 days to 8 days (p=0.071) over a time period. Postoperative hospital stay was significantly reduced from 24 days to 14 days (p=0.026). CONCLUSION Utilization of a stapling technique and closed active drain significantly reduces postoperative hospital stay.