IL(interleukin)-18 is known to induce proliferation of Vδ2+ T cells and expression of CD56, resulting in enhancement of cytotoxic activity. We focused on the expression of CD56 and the direct action of IL-18 on Vδ2+ T cells to evaluate the importance of IL-18 for developing Vδ2+ T cells-based adoptive immunotherapy. Peripheral blood mononuclear cells (PBMCs) were purified from heparinized blood of healthy donors and cancer patients. CD56− Vδ2+ T cells isolated from healthy subjects were cultured with IL-2 and IL-18 or with IL-2 alone. The number of CD56− Vδ2+ cells increased compared with those with IL-2 alone. However, this increase was not statistically significant. CD56− Vδ2+ T cells derived from CD56+-depleted PBMCs were stimulated by phosphoantigens and cultured with IL-2 and IL-18, and showed significantly stronger cytotoxic activity than resultant CD56+ Vδ2+ T cells. IL-18 promotes the proliferation of Vδ2+ T cells from PBMCs of ovarian cancer patients. Thus, IL-18 is worth to be considered as a strong candidate in the development of effective cancer immunotherapy.
We constructed inducible expression system of Susd2 gene which we previously identified as a novel tumor suppressor gene. Here we report the growth inhibition of colorectal cancer HCT116 cells and fibrosarcoma HT1080 cells by inducible expression of Susd2 protein from HCT/G5Susd2 and HT/G5Susd2 cells by infection of Ad/G4VP2, as revealed by colony formation and growth behavior. Thus, we found that Susd2 inhibits growth of cancer cells and this information may benefit to patients with malignant diseases.
Background: The tight junction protein claudin is abnormally regulated in several human cancers. In particular, claudin-4 is frequently overexpressed in several neoplasias, including breast, pancreatic, ovarian, and prostate cancers. This study examined the relationship of the relative expression of the claudin-4 gene to the clinicopathological factors and outcomes in patients with colorectal cancer (CRC).
Methods: We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated CRC. The relative expression of claudin-4 mRNA in cancer and in normal adjacent mucosa was measured by quantitative real-time reverse-transcriptase polymerase chain reaction.
Results: The claudin-4 expression was higher in cancer tissue than in adjacent normal mucosa. The claudin-4 expression was related to the cancer location. The overall survival at five years differed significantly between patients with a high claudin-4 expression and those with a low expression.
Conclusion: The overexpression of claudin-4 was considered a useful predictor of outcomes in patients with CRC.
Background: Conversion therapy is a surgical option for unresectable gastric cancer in cases wherein non-curative factors are initially managed by induction chemotherapy. However, the indications for resection remain unclear. Thus, this study aimed to assess the feasibility and efficacy of conversion therapy, based on the data from our facility.
Methods: Patients (n=97) with unresectable gastric cancer received chemotherapy in our facility between January 2010 and August 2016. Surgical resection was performed in 16 of them after chemotherapy had rendered the tumor resectable. We retrospectively examined clinicopathological variables and oncologic outcomes in these 16 cases.
Results: Of the 16 patients who underwent resection, R0 resection was possible in 15 patients, whereas R1 resection was performed in the remaining 1 patient. Postoperative complications arose in 6 patients (37.5%) but with no mortality. The median overall survival (OS) in the conversion therapy patients (n=16) was 50 months. Among the patients who underwent conversion therapy, univariate analysis showed that the patients with type 4 gastric cancer had a poor prognosis (P=0.0009).
Conclusion: The conversion therapy may improve OS in only some of the patients who responded to induction chemotherapy, our results suggest that conversion therapy does not improve the outcomes in patients with type 4 gastric cancer.
Background/Aim: Postoperative delirium is a common complication which is associated with increased postoperative mortality and morbidity. The aim of this study was to evaluate the incidence and predictors of postoperative delirium using data from a phase II clinical trial.
Patients and Methods: We analyzed the cases that were enrolled in randomized clinical trial to evaluate TJ-54 (Yokukansan, a traditional Japanese medicine [Kampo]) for the prevention and/or treatment of postoperative delirium (UMIN000005423). The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) was used to diagnose postoperative delirium.
Results: A total of 167 patients were registered, delirium was observed in 9% of them. High age over 80 and low MMSE less than 27 were identified as significant independent risk factors.
Conclusion: Surgeon should pay attention to the possible development of postoperative delirium in patients aged over 80 with a low MMSE less than 27 in performing surgery for gastrointestinal malignancies.
Although the survival of patients with liver metastases was previously extremely poor, the introduction of novel chemotherapeutic agents, such as oxaliplatin, has increased the median survival of these patients. S-1 has been reported to show strong antitumor activity in various types of cancer, such as colorectal cancer (CRC), and its feasibility in combination with oxaliplatin (SOX) has been reported to have a promising efficacy with fair tolerability in patients with metastatic CRC. We here present a case of synchronous liver metastasis of CRC in which a complete clinical response was successfully achieved by SOX plus bevacizumab (BV). CT scan results confirmed a clinical complete response after eight cycles, and monotherapy with S-1 was ongoing for 6 months. Currently, there was no evidence of any recurrent or metastatic lesions. We found that a regimen of SOX plus BV is a safe and effective treatment for metastatic CRC that does not require central venous access.
Background: Palbociclib is reported to improve progression-free survival (PFS) in patients with estrogen-receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC). However, evidence of the effects of palbociclib in heavily treated patients is limited. The present study aimed to determine the effects and toxicity of palbociclib in heavily pretreated patients and to find the differences between the patients treated with palbociclib in upfront line and those with in later-line.
Methods: This retrospective, single-center, observational study enrolled 26 patients with ER-positive, HER2-negative MBC who started palbociclib (125 mg) plus endocrine therapy between December 2017 and July 2018. These patients were divided into 2 groups, upfront (<3) and later-line groups (≥4 lines prior therapy). Progression-free survival (PFS) estimated using the Kaplan-Meier method was compared between 14 patients who received upfront-line therapy and 12 who received later-line therapy.
Results: Among the 26 patients, 22 (85%) had visceral metastasis. The median number of prior treatment lines for MBC was 3.5 and the median follow-up was 5.1 months. Median PFS was 3.6 months in later-line group, and PFS was significantly shorter than in the upfront-line group (p = 0.046, median PFS: not reached in upfront line group). The incidences of grade 3/4 neutropenia were 86% and 83% in the upfront- and later-line groups, respectively. One patient developed febrile neutropenia. The treatment schedule was interrupted in 13 (93%) and 11 (92%) patients in the upfront- and later-line groups, respectively. The number of the patients who required dose reduction was higher in later-line group than upfront-line group (67% vs. 57%).
Conclusion: Although the toxicity of palbociclib is tolerable with a low incidence of febrile neutropenia, palbociclib is less-effective for heavily pretreated patients in comparison with lightly-pretreated patients. Our findings indicated that palbociclib could be used as a front-line treatment for MBC.
We report a case of adenosquamous carcinoma of the gallbladder with intermittent high fever and positive findings of a primary lesion and regional lymph nodes on positron emission tomography (PET-CT). The patient was a 62-year-old man who visited a local clinic with a high fever. His white blood cell count (WBC) and serum level of C-reactive protein (CRP) were elevated. However, the origin of the fever was not identified. He was diagnosed with an unidentified fever and admitted to our hospital. Abdominal enhanced CT revealed a gallbladder tumor invading the liver and enlarged regional lymph nodes. PET-CT showed positive findings of a local lesion and regional lymph nodes. He was diagnosed with gallbladder cancer with lymph node metastases. The patient underwent hepatic resection of segments 4a+5 with radical lymph node dissection as curative surgery. Preoperative drainage of the gallbladder to improve the high fever was not performed. The post-operative course was uneventful. The severe, intermittent high fever improved immediately, and the levels of WBC and CRP levels decreased to the normal ranges after surgery. The histological findings of the resected specimen revealed that the tumor was an adenosquamous carcinoma invading the liver without any lymph node metastases or inflammatory changes. The radical and aggressive resection contributed to improving the uncontrollable fever as a paraneoplastic syndrome.
Introduction: As patients with metastatic colorectal cancer (mCRC) have various clinical backgrounds and the treatment strategies that are applied in their management are diverse, it is difficult to accurately estimate their prognosis. We conducted this study to establish a prognostic nomogram for mCRC patients using a population-based database.
Materials and Methods: In this population-based, multicenter, retrospective, observational cohort study, we aimed to enroll 1,500 patients from all nine designated cancer hospitals across Fukushima prefecture from January 2008 to December 2015. Patients with a metastatic lesion according to the TNM classification (AJCC/TNM 8th) were eligible for inclusion. The primary outcome was overall survival. The last day of follow-up was December 31, 2017. We investigated the clinical significance of the following variables: age, sex, body mass index, Charlson comorbidity index, activities of daily living, location of colorectal cancer, degree of differentiation, TNM stage, number of distal metastatic organs, severity of each metastatic organ, symptoms from the primary lesion, laboratory markers, and method of treatment.
Discussion: This is the first prognostic nomogram of patients with mCRC created from a population-based cohort.