Hiromichi Yamai

Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo

The antineoplastic effects of combinations of anticancer drugs (5‐fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST‐8 (2‐(2‐methoxy‐ 4‐nitrophenyl)‐3‐(4‐nitrophenyl)‐5‐(2,4‐disulfophenyl)‐2H‐tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES‐2cells) by combinational use of 5‐fluorouracil. JAE and 5‐fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES‐2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES‐2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5‐fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5‐fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5‐fluorouracil and JAE were less than those in mice treated with 5‐fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5‐fluorouracil on esophageal cancer.

Sentinel Lymph Node Biopsy Using Intraoperative Indocyanine Green Fluorescence Imaging Navigated with Preoperative CT Lymphography for Superficial Esophageal Cancer

BackgroundThe sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer.MethodsSubjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG.ResultsLymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures.ConclusionsPreoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.

A New Candidate Supporting Drug, Rikkunshito, for the QOL in Advanced Esophageal Cancer Patients with Chemotherapy Using Docetaxel/5-FU/CDDP

Purpose. Docetaxel/5-FU/CDDP (DFP) therapy is a useful treatment for advanced esophageal cancer. However, adverse reactions such as chemotherapy-induced nausea and vomiting (CINV) interfere often with continuation of the chemotherapy. We investigated the efficacy of rikkunshito (TJ-43) on CINV. Methods. Nineteen patients who were going to undergo DFP therapy were enrolled. They were assigned to the following two groups: a TJ-43-treated group and -nontreated group. The following parameters were compared between the 2 groups: (1) the frequency of symptoms occurred, (2) vomiting, nausea, and anorexia score, and (3) QOL score. Results. The incidence of symptoms was lower in the TJ-43-treated group than that in the control group. The nausea score of the TJ-43-treated group was significantly lower than that of the control group. In the QOL score, the mood score and the ADL score decreased significantly in the control group. Conclusion. We recommend TJ-43 administration in patients undergoing DFP chemotherapy.

Preoperative chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil for stage II/III squamous cell carcinoma of the esophagus

BackgroundDocetaxel is a powerful anticancer agent for esophageal cancer. Preoperative combined chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil (DFP) followed by surgery is expected to improve the survival of patients with resectable esophageal squamous cell carcinoma.MethodsClinical stage II/III squamous cell carcinoma patients who received DFP followed by esophagectomy (NAC group, n = 13) were compared retrospectively with patients who received surgery without preoperative DFP (Surgery group, n = 12). Not only the efficacy and toxicity of initial chemotherapy but also morbidity and survival after esophagectomy were assessed.ResultsOf 13 patients, the overall response rate was 92.3%; 30.8% (4/13) patients had CR, 61.5% (8/13) PR, 7.7% (1/13) SD, and 0 (0/13) PD. The 4 patients who achieved a pathological complete response (pCR) included 1 with cT4N1M0, 2 with cT3N1M0, and 1 with cT3N0M0. More than grade 3 toxicity of neutropenia and stomatitis occurred in 15.4% and 23.1% of patients, respectively. Leakage was 23.1% in the NAC group and 8.3% in the Surgery group. No treatment-related deaths occurred in the NAC group.ConclusionsThis regimen as preoperative chemotherapy seemed to provide a high response rate and a favorable survival benefit with acceptable toxicity and morbidity. To validate the clinical significance of this protocol, a randomized trial is essential.

Hepatoid Adenocarcinoma of the Extrahepatic Bile Duct in a Patient with Polysplenia Syndrome

Hepatoid adenocarcinoma (HAC) is a rare subtype of extrahepatic adenocarcinoma that is characterized by its morphological and functional similarities to hepatocellular carcinoma. We herein present a novel case of HAC arising from the extrahepatic bile duct in a 75-year-old Japanese woman with polysplenia syndrome. This is the second reported case of HAC arising from this site. The tumor induced jaundice and hemobilia. A total of four isolated intraductal polypoid masses of HAC were found. No recurrence was seen five months after surgery. Further reports of similar cases will be needed to clarify the clinical characteristics and the prognosis of this malignancy.