Kazuya Nakagawa

Immunological Impact of Neoadjuvant Chemoradiotherapy in Patients with Borderline Resectable Pancreatic Ductal Adenocarcinoma

BackgroundLittle is known about the immunological effect of neoadjuvant chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal adenocarcinoma. The objective of this study was to examine the immunological modifications induced by NACRT in patients with pancreatic cancer.MethodsFifty-two patients with pancreatic cancer who underwent surgical resection were enrolled in this study. NACRT was administered to 22 patients, whereas the other 30 patients underwent surgical resection without NACRT. The resected tumor specimens were analyzed for the presence of tumor-infiltrating lymphocytes by using immunohistochemical staining for CD4, CD8, CD68, CD163, Foxp3, and major histocompatibility complex class I (MHC class I) antigen.ResultsThe number of CD4+ and CD8+ lymphocytes was significantly higher in patients who received NACRT than in those who did not receive NACRT. No significant difference in MHC class I expression was observed between the groups. In the NACRT group, patients with a high accumulation of CD8+ cells experienced longer overall survival than those with a low number of CD8+ cells.ConclusionsNACRT may induce the accumulation of CD4+ and CD8+ cells in the tumor microenvironment and a high accumulation of CD8+ cells might be a good prognostic marker for pancreatic cancer treated with NACRT.

Two-stage hepatectomy with effective perioperative chemotherapy does not induce tumor growth or growth factor expression in liver metastases from colorectal cancer

BACKGROUND Although short- and long-term results have been described in previous reports of 2-stage hepatectomy, growth activity in metastases resected at the first versus second hepatectomy has not been compared. METHODS We analyzed growth activity of liver metastases from colorectal cancers resected at first and second hepatectomy by real-time reverse-transcription polymerase chain reaction and immunohistochemistry in 21 patients undergoing 2-stage hepatectomy to justify the 2-stage approach. RESULTS Of 24 patients planned to undergo 2-stage hepatectomy for colorectal liver metastases, 21 had completion of both stages. Although maximum tumor size and serum carcinoembryonic antigen before and after the first procedure did not differ, volume of the future liver remnant increased after the first procedure. Ki67 and proliferating cell nuclear antigen positivity rates were comparable between initially and subsequently resected tumors (P = .09 and P = .83, respectively). Expression of mRNA (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) in initially versus subsequently resected tumors for cyclin D1 (4.27 ± 1.29 vs 6.52 ± 2.23; P = .90), cyclin E1 (24.18 ± 16.81 vs 10.53 ± 2.28; P = .60), hepatocyte growth factor (3.16 ± 1.42 vs 0.58 ± 0.15; P = .11), basic fibroblast growth factor (5.42 ± 1.54 vs 5.92 ± 3.33; P = .13), epidermal growth factor (19.56 ± 14.76 vs 9.07 ± 4.54; P = .74), and transforming growth factor-α (2.63 ± 1.02 vs 2.07 ± 1.15; P = .29) showed no differences between the 2 time points. CONCLUSION Two-stage hepatectomy did not seem to induce tumor growth activity or growth factor expression. The 2-stage strategy in combination with effective preoperative chemotherapy is a valuable strategy for colorectal metastases.

Predictive factors for bile leakage after hepatectomy for hepatic tumors: A retrospective multicenter study with 631 cases at Yokohama Clinical Oncology Group (YCOG)

International Study Group of Liver Surgery (ISGLS) proposed the standardized definition for bile leakage (BL) after hepatectomy (Hx) at 2011 to precisely perceive incidence and predictive factors of this critical condition.

Debulking surgery followed by intraarterial 5-fluorouracil chemotherapy plus subcutaneous interferon alfa for massive hepatocellular carcinoma with multiple intrahepatic metastases: a pilot study.

BACKGROUND The prognosis in advanced hepatocellular carcinoma (HCC) with multiple intrahepatic metastases is extremely poor. Combination therapy with subcutaneous interferon (IFN) alfa and intraarterial 5-fluorouracil was reported to be effective against such advanced HCC. We describe results of debulking surgery followed by combination therapy with IFN alfa and 5-FU for massive HCC with multiple intrahepatic metastases. METHODS In 27 HCC patients with massive tumors and multiple intrahepatic metastases, we performed combination therapy with IFN alfa and 5-FU after maximal liver tumor resection. RESULTS Mean patient age was 63.3 years. Including intrahepatic metastases, tumors numbered 5 or more in 17 patients (63%). Portal or hepatic vein branches were invaded in 22 (81%). The mean maximum tumor diameter was 102 mm. Among 24 patients whose results were analyzed, an objective response by residual intrahepatic metastases was observed in 13 (54%; complete response in 12, and partial response in 1). Overall 1-, 3-, and 5-year survival was 73.2%, 38.7%, and 38.7%, respectively; 1-, 3-, and 5-year progression-free rates were 38.2%, 22.3%, and 22.3%. CONCLUSIONS Debulking surgery followed by IFN alfa and 5-FU combination chemotherapy offers possibility of long-term survival despite massive HCC with multiple intrahepatic metastases.

Detection of gas components as a novel diagnostic method for colorectal cancer

The fecal occult blood test (FOBT) is widely accepted as the most economic and non‐invasive screening method for colorectal cancer (CRC). However, the FOBT is inconvenient because it requires a fecal sample and shows limited accuracy. Alternatively, we hypothesized that fecal gas compounds from bowel movements may be a non‐invasive biomarker for CRC.

Abstract 3365: High infiltration of mast cells predicts worse outcome following resection of colorectal liver metastases

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background. Tumor infiltrating mast cells (MCs) are considered a primary host immune response against cancer. From some reports, their roles are not determined yet and vary with the type of cancer. There was no report about tumor infiltrating MCs in colorectal liver metastases (CRLM). Aim of this study is to determine whether peritumoral MCs infiltration of CRLM become a predictive factor of survival after curative resection of CRLM. Methods. A total of 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010 were included in our retrospective study. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The different types of immune cells in the 3 most abundant peritumoral areas and normal liver areas were counted, and the each cell number was utilized to predict a good prognosis. “Peritumoral” was defined as the division between normal liver tissue and the tumor. The cut-off point of each immune cell number was calculated to select a group of good prognosis after liver resection by using the Youden index from the ROC curve. Using these cut-off points, 135 patients were classified into 2 groups and statistic difference of prognosis was calculated by Kaplan-Meier analysis and the log rank test, and statistic difference of clinic-pathological feature was calculated by chi square test and cox proportional hazard regression. This study was approved by the Yokohama City University Ethics Committee. Results. Cancer-specific survival (CSS) at 1, 3, and 5 years were 91.0%, 62.4%, and 37.4%, respectively. The cut-off points were fixed 26 of MCs, 176 of Mφs, and 17 of DCs. Only the cut-off point of MCs classified 2 groups which showed significantly different prognosis. 54% (73 of 135) of patients were classified in the high MC group. Five-year disease free survival (DFS) of the high MC group and the low MC group was 1.6% and 42.6%, respectively (P<0.001) and CSS of the 2 was 38.1% and 55.6%, respectively (P<0.01). In the clinicopathological feature, only the peritumoral vessel density showed significant difference, significantly higher in the high MC group. Multivariate analyses indicated that hypoalbuminemia and high peritumoral MC infiltration were significant predictors of unfavorable CSS. Conclusion. High peritumoral MC infiltration predicts poor prognosis in patients after resection of liver metastases of colorectal cancer. High MC infiltration might be related with peritumoral neovascularization. Citation Format: Shinsuke Suzuki, Yasushi Ichikawa, Kazuya Nakagawa, Takafumi Kumamoto, Ryutaro Mori, Ryusei Matsuyama, Kazuhisa Takeda, Mitsuyoshi Ota, Kuniya Tanaka, Itaru Endo. High infiltration of mast cells predicts worse outcome following resection of colorectal liver metastases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3365. doi:10.1158/1538-7445.AM2015-3365