Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein.

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.

Evaluating a combination treatment of NK cells and reovirus against bladder cancer cells using an in vitro assay to simulate intravesical therapy.

Intravesical treatment using either reovirus or natural killer (NK) cells serves as an efficient strategy for the treatment of bladder cancer cells (BCCs); however, corresponding monotherapies have often shown modest cytotoxicity. The potential of a locoregional combination using high-dose reovirus and NK cell therapy in an intravesical approach has not yet been studied. In this study, we evaluated the effectiveness of reoviruses and expanded NK cells (eNK) as potential strategies for the treatment of bladder cancer. The anti-tumor effects of mono-treatment with reovirus type 3 Dearing strain (RC402 and RP116) and in combination with interleukin (IL)-18/-21-pretreated eNK cells were investigated on BCC lines (5637, HT-1376, and 253J-BV) using intravesical therapy to simulate in vitro model. RP116 and IL-18/-21-pretreated eNK cells exhibited effective cytotoxicity against grade 1 carcinoma (5637 cells) when used alone, but not against HT-1376 (grade 2 carcinoma) and 253J-BV cells (derived from a metastatic site). Notably, combining RP116 with IL-18/-21-pretreated eNK cells displayed effective cytotoxicity against both HT-1376 and 253J-BV cells. Our findings underscore the potential of a combination therapy using reoviruses and NK cells as a promising strategy for treating bladder cancer.

Genetic specificity study using next-generation sequencing (NGS) of peritoneal metastatic colorectal cancer compared to primary colorectal cancer.

BACKGROUND: In patients with colorectal cancer, peritoneal metastases are the second most frequent metastatic lesion after liver metastases. Peritoneal metastases have a very poor prognosis, with a median survival time of 5-7 months. Currently, there is a lack of research on the genetic differences between primary colorectal cancer and peritoneal metastases. Therefore, we aimed to identify their genetic characteristics through a cancer panel test using next-generation sequencing. OBJECTIVE: We aim to investigate the specificity of genetic variants in primary colorectal cancer and peritoneal metastases. METHODS: We recruited patients with stage I, II, and III primary colorectal cancer and peritoneal metastases for genetic analysis using NGS. Samples were collected from patients who underwent surgery at Dankook University Hospital and consented to genetic testing. NGS was performed using a cancer panel. RESULTS: Among 36 patients with primary cancer, TP53 gene mutation was identified the most in 25 patients (69%), followed by APC gene mutation in 19 patients (53%), and KRAS gene mutation in 17 patients (47%). In the peritoneal metastasis patient group, unlike the primary cancer patient group, KRAS gene mutations were the most common 6 patients (55%), followed by TP53 gene mutations in 4 patients (36%) and PIK3CA gene mutations in 2 patients (18%). CONCLUSION: The small number of surgical cases of peritoneal metastases was a limitation of our sample size. Nevertheless, we identified differences in the alterations of specific genes between primary and peritoneal metastases. Acquiring additional cases and collecting more data will provide deeper insights into these cancers.

Apoptotic activity of genipin in human oral squamous cell carcinoma in vitro by regulating STAT3 signaling.

Genipin, a natural compound derived from the fruit of Gardenia jasminoides Ellis, was reported to have activity against various cancer types. In this study, we determined the underlying mechanism for genipin-induced cell death in human oral squamous cell carcinoma (OSCC). The growth-inhibitory effects of genipin in human OSCC cells was examined by the Cell Counting Kit-8 and soft agar assays. The effects of genipin on apoptosis were assessed by nuclear morphological changes by 4',6-diamidino-2-phenylindole staining, measurement of the sub-G1 population, and Annexin V-fluorescein isothiocyanate/propidium iodide double staining. The underlying mechanism of genipin activity was analyzed by western blot analysis, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry, and quantitative real-time polymerase chain reaction. Genipin inhibited the growth of OSCC cells and induced apoptosis, which was mediated by a caspase-dependent pathway. Genipin reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and its nuclear localization. Furthermore, inhibition of p-STAT3Tyr705 levels following genipin treatment was required for the reduction of survivin and myeloid cell leukemia-1 (Mcl-1) expression, leading to apoptotic cell death. The genipin-mediated reduction in survivin and Mcl-1 expression was caused by transcriptional and/or posttranslational regulatory mechanisms. The results provide insight into the regulatory mechanism by which genipin induces apoptotic cell death through the abrogation of nuclear STAT3 phosphorylation and suggest that genipin may represent a potential therapeutic option for the treatment of human OSCC.

Neuropilin-2 acts a critical determinant for epithelial-to-mesenchymal transition and aggressive behaviors of human head and neck cancer.

PURPOSE: Neuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor. METHODS: In silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2. RESULTS: NRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells. CONCLUSIONS: These findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients.

Dual-Armed Oncolytic Myxoma Virus Encoding IFN-γ and CD47 Promotes Lymphocyte Infiltration and Tumor Suppression of Syngeneic Murine Melanoma.

Myxoma virus (MyxV) is a rabbit-specific poxvirus. However, its ability to selectively target tumor cells has established it as a safe and effective anticancer therapy. To strengthen its preclinical efficacy, transgenes that can prolong cancer cell infection and enhance anti-tumor effector functions are currently being investigated. We engineered MyxV armed with CD47, to turn on a 'do not eat me' signal within infected cells with actively replicating viruses, and with IFN-γ to further activate host immune anticancer responses. Tumor suppressive activities were significantly enhanced by the dual-armed MyxV_CD47/IFN-γ compared to parental MyxV or single-armed MyxV_CD47 or MyxV_IFN-γ. In addition, significant increases in IFN-γ+ CD8+T-cells and CD4+ T-cells populations within tumor-infiltrating lymphocytes (TIL) were observed after MyxV_CD47/IFN-γ treatment. Notably, all groups treated with MyxV showed a marked reduction in Foxp3+ CD4+ regulatory T-cells (Tregs) within TIL. We also show that MyxV infection induces PD-L1 up-regulation in cancer cells, and combinational treatment of MyxV with anti-mouse PD-L1 antibodies (αPD-L1) further controlled tumor burden and increased survival in the syngeneic melanoma model B16F10. Our data demonstrate that a CD47 and IFNγ dual-armed MyxV is an effective oncolytic viral immunotherapeutic. These findings strongly support further preclinical investigations to develop next-generation MyxV-based immunotherapy approaches.

Comparison of genetic variation between primary colorectal cancer and metastatic peritoneal cancer.

BACKGROUND: Among cancer metastases by primary colorectal cancer (CRC), peritoneal metastasis is the second most common metastatic lesion after liver metastasis. In treating metastatic CRC, it is very important to differentiate targeted-therapy and chemotherapy according to the characteristics of each lesion because the genetic variation of the primary and metastatic lesions are different. However, there are few studies of genetic characteristics on peritoneal metastasis caused by primary CRC, so molecular-level studies are continuously required. OBJECTIVE: We propose an appropriate peritoneal metastasis treatment policy by identifying the genetic characteristics between primary CRC and synchronous peritoneal metastatic lesions. METHODS: Primary CRC and synchronous peritoneal metastasis samples were analyzed in pairs from six patients using Comprehensive Cancer Panel (409 cancer-related genes, Thermo Fisher Scientific, USA) and next-generation sequencing (NGS). RESULTS: The mutations were commonly found on the KMT2C and THBS1 genes in both primary CRC and peritoneal metastasis. The PDE4DIP gene was mutated in all cases except for on a sample of peritoneal metastasis. As a result of analysis using the mutation database, we confirmed that the gene mutations of primary CRC and the peritoneal metastasis derived from it showed the same tendency, although we did not accompany the gene expression level or epigenetic study. CONCLUSION: It is thought that the treatment policy through molecular genetic testing of primary CRC can also be applied to peritoneal metastasis treatment. Our study is expected to be the basis for further peritoneal metastasis research.

Cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastasis of colorectal cancer: long-term follow-up results at a single institution in Korea.

PURPOSE: This study aimed to examine the 7-year follow-up results of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for peritoneal metastasis (PM) of colorectal cancer. METHODS: We performed 54 cases of CRS and IPC in 53 patients with PM of colorectal cancer from December 2011 to December 2013. We prospectively collected data and analyzed peritoneal carcinomatosis grade, completeness of cytoreduction, and long-term follow-up (median, 10 [range, 2-92] months) results. RESULTS: The mean peritoneal cancer index was 15 (1 ~ 35), and complete cytoreduction was possible in 35 (64.8%) patients. Excluding the four patients who died, 11 (22.4%) out of the 49 patients were alive at the time of the last follow-up, and the overall median survival period was 10.3 months. The overall 2- and 5-year survival rates were 31% and 17%, respectively. Patients with complete cytoreduction had a median survival period of 22.6 months, which was significantly longer than that for patients without complete cytoreduction (3.5 months) (P < 0.001). The 5-year survival rate for patients with complete cytoreduction was 24%, and four patients were still alive without disease. CONCLUSIONS: CRS and IPC show a 5-year survival rate of 17% in patients with PM of colorectal cancer. A possibility of long-term survival is observed in a selected group. Multidisciplinary team evaluation for careful patient selection and CRS training program to achieve complete cytoreduction are significantly important factors in improving survival rate.

Targeting tumor-intrinsic PD-L1 suppresses the progression and aggressiveness of head and neck cancer by inhibiting GSK3ß-dependent Snail degradation.

PURPOSE: PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. METHODS: The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. RESULTS: Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3ß-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3ß/Snail/vimentin axis. CONCLUSION: The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.

Peritoneal metastatic mixed adenoneuroendocrine carcinoma treated with cytoreduction surgery and hyperthermic intraperitoneal chemotherapy: a case report.

A 61-year-old man presented with abdominal distension without any symptoms. On colonoscopy and computed tomography findings, it was clinically diagnosed as peritoneal metastasis of sigmoid colon cancer, and diagnostic laparoscopy was performed. Only the peritoneum was partially resected, and the pathology was signet ring cell carcinoma with predominantly local mucinous carcinoma component. However, the patient complained of persistent symptoms and, despite the progress of chemotherapy, the peritoneal dissemination worsened, and additional cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) was performed. Mixed adenoneuroendocrine carcinomas (MANECs) were reported in the appendix with perforated visceral peritoneum. After additional chemotherapy, the patient was discharged. Patients with advanced MANEC with peritoneal spreading may benefit from aggressive treatment by cytoreduction surgery with HIPEC, followed by intravenous chemotherapy.

470 nm LED Irradiation Inhibits the Invasiveness of CD133-positive Human Colorectal Cancer Stem Cells by Suppressing the Cyclooxygenase-2/prostaglandin E2 Pathway.

BACKGROUND/AIM: Recurrence and metastasis of cancer caused by cancer stem cells (CSCs) is a challenge to overcome. Low level laser therapy is a new treatment strategy to suppress their invasiveness. We have assessed the inhibitory effects of 470 nm blue LED on the invasiveness of them to determine the molecular mechanisms of anti-invasiveness. MATERIALS AND METHODS: The effects of blue LEDs on their viability, proliferation and invasion were analyzed using MTT and transwell methods. In addition, the anti-invasiveness effect of blue LED on them was evaluated by zymography, semi-quantitative RT-PCR and western blot analysis. RESULTS: Irradiation with blue LED at 3 J/cm2 resulted in inhibition of their viability, proliferation and invasiveness. Their matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were reduced by blue LED irradiation. Semi-quantitative RT-PCR also showed similar results. In addition, western blotting analyses showed that cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis were significantly inhibited by LED irradiation in CD133+ colorectal CSCs. CONCLUSION: Down-regulation of the COX-2/PGE2 signaling pathway by blue LED irradiation led to reduce expression of MMP-2 and MMP-9, inhibiting the invasiveness of CD133+ colorectal CSC.

YM155, specific survivin inhibitor, can enhance artesunate-induced cytotoxicity in HCT116 colon cancer cells.

Purpose: A water-soluble variant of the artemisinin called artesunate, approved as an antimalarial agent, can induce cell death on various cancer cell types. We studied the mechanism of cell death of artesunate on HCT116 colorectal cancer cells. Methods: We treated HCT116 colon cancer cells with artesunate, holo-transferrin, deferoxamine mesylate, ferrostatin, necrostatin-1, and YM155. We observed the growth inhibition of artesunate on HCT116 colon cancer cells by morphologic findings. Inhibition of cell growth was assessed by MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay and long-term growth inhibition by colony-forming assay. Apoptosis was investigated by flow cytometry and Western blot analysis. Results: Artesunate inhibited the proliferation of HCT116 colon cancer cells effectively. Co-treatment with YM155, a specific survivin inhibitor, enhanced the artesunate-induced cell death. Co-treatment with the iron-chelating agent deferoxamine rescued artesunate induced cell death and increased long-term cell survival and proliferation. Conclusion: In this study, we demonstrated that artesunate-induced cytotoxicity in HCT116 colon cancer cells by suppressing the expression of survivin and partially by ferroptosis. Our findings suggest that the co-treatment artesunate with YM155 can induce more potent cell death on HCT116 colon cancer cells and shows new insight for the treatment of colorectal cancer patients.

Comparison of library construction kits for mRNA sequencing in the Illumina platform.

BACKGROUND: The emergence of next-generation sequencing (NGS) technologies has made a tremendous contribution to the deciphering and significance of transcriptome analysis in biological fields. Since the advent of NGS technology in 2007, Illumina, Inc. has provided one of the most widely used sequencing platforms for NGS analysis. OBJECTIVE: Although reagents and protocols provided by Illumina are adequately performed in transcriptome sequencing, recently, alternative reagents and protocols which are relatively cost effective are accessible. However, the kits derived from various manufacturers have advantages and disadvantages when researchers carry out the transcriptome library construction. METHODS: We compared them using a variety of protocols to produce Illumina-compatible libraries based on transcriptome. Three different mRNA sequencing kits were selected for this study: TruSeq® RNA Sample Preparation V2 (Illumina, Inc., USA), Universal Plus mRNA-Seq (NuGEN, Ltd., UK), and NEBNext® Ultra™ Directional RNA Library Prep Kit for Illumina® (New England BioLabs, Ltd., USA). We compared them focusing on cost, experimental time, and data output. RESULTS: The quality and quantity of sequencing data obtained through the NGS technique were strongly influenced by the type of the sequencing library kits. It suggests that for transcriptome studies, researchers should select a suitable library construction kit according to the goal and resources of experiments. CONCLUSION: The present work will help researchers to choose the right sequencing library construction kit for transcriptome analyses.

Novel Discovery of LINE-1 in a Korean Individual by a Target Enrichment Method.

Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy as Treatment Options for Peritoneal Metastasis of Advanced Gastric Cancer.

PURPOSE: This study aimed to examine the outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis (PM) of advanced gastric cancer (AGC). MATERIALS AND METHODS: Between May 2015 and June 2017, 38 CRS and HIPEC procedures were performed in patients with PM of AGC at the Dankook University Hospital. We prospectively collected and analyzed data regarding PM grade, morbidity and mortality rates, and short-term follow-up results (median, 13.5 months). RESULTS: The mean peritoneal cancer index was 15 (range, 0-39). Complete cytoreduction was achieved in 21 patients (55.2%), whereas complications occurred in 16 (42.1%) and 2 (5.7%) patients died. The overall median patient survival time was 19 months. The patients who underwent complete cytoreduction had a median survival time of 26 months, which was significantly longer than the median survival time of 16 months in the patients who did not undergo complete cytoreduction (P=0.006). CONCLUSIONS: CRS with HIPEC may have a beneficial effect in patients with PM of AGC. However, the rates of complications and mortality associated with this combined therapeutic approach are high. Therefore, this treatment should be performed only in selected patients by surgeons experienced in the field of gastric cancer with PM.

Urinary Bladder Injury During Colonoscopy Without Colon Perforation.

We report a case of urinary bladder perforation during colonoscopy. A 67-year-old female, who had undergone a transabdominal hysterectomy for uterine myomas 15 years ago, visited the emergency department with complaint of abdominal pain after a screening colonoscopy. Laparoscopic examination revealed severe adhesion between the sigmoid colon and the urinary bladder. The urinary bladder wall was weakened, and several perforation sites were found. The surgery was converted to a laparotomy. After a thorough examination, we performed primary repair for the perforation sites, followed by an omentopexy.

Cytoreductive surgery and intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal cancer: 2-year follow-up results at a single institution in Korea.

PURPOSE: The purpose of this study was to examine 2-year follow-up results of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis (PC) of colorectal cancer. METHODS: We performed 54 cases of CRS and IPC in 53 patients with PC of colorectal cancer from December 2011 to December 2013. We collected data prospectively and analyzed the grade of PC, morbidity and mortality, and short-term follow-up (median, 10 months; range, 2-47 months) results. RESULTS: Mean peritoneal cancer index (PCI) was 15 (range, 1-35), and complete cytoreduction was possible in 35 patients (64.8%). Complications occurred in 25 patients (46.3%) and mortality occurred in 4 patients (7.4%). Excluding the 4 mortalities, 17 patients out of 49 patients (31.5%) were alive at the time of the last follow-up and the overall median survival was 10.3 months. Patients with complete cytoreduction had a median survival of 22.6 months, which was significantly longer than the median survival of 3.5 months for patients without complete cytoreduction (P < 0.001). PCI grade, CCR grade, cell type, and postoperative chemotherapy were significant prognostic factors by univariate analysis. Positive independent prognostic factors by multivariate analysis included PCI grade and postoperative chemotherapy. CONCLUSION: CRS and IPC increased the survival of patients with low PCI and postoperative systemic chemotherapy was mandatory. However, this combined therapeutic approach showed high rate of complications and mortality. Therefore, this aggressive treatment should be performed in only selected patients by considering the general condition of the patient and the extent of PC.

Clinical Practice in the Use of Adjuvant Chemotherapy for Patients with Colon Cancer in South Korea: a Multi-Center, Prospective, Observational Study.

BACKGROUND: Adjuvant chemotherapy is a crucial part of treatment for patients with locally advanced colon cancer. This study was conducted to investigate the actual practice in the use of adjuvant chemotherapy for patients with high-risk stage II or stage III colon cancer in South Korea. METHODS: This was a 24-month open-label, prospective, observational study conducted at 12 centers across South Korea. Patients with high-risk stage II and stage III colon cancer receiving adjuvant chemotherapy after curative surgery were included, and data were collected at baseline, third, and sixth month. RESULTS: A total of 246 patients were included in the analyses. Of five available regimens (FOLFOX, CAPOX, 5-FU/LV, capecitabine, and UFT/LV), FOLFOX was most commonly used (82.5%). Investigators indicated the "efficacy" as the major cause for selecting FOLFOX or CAPOX. For 5-FU/LV, capecitabine, or UFT/LV, the "safety" or "patient's characteristics (age, comorbidity, and stage)" was one of the most important selecting factors. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. Hematologic toxicities were the most common cause of dose adjustment and treatment delay. CONCLUSIONS: In South Korea, FOLFOX was the most commonly used regimen for adjuvant chemotherapy and its efficacy was the main cause for selecting this regimen. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX.

Peritoneal metastatic goblet-cell carcinoid tumor treated with cytoreductive surgery and intraperitoneal chemotherapy.

We report a case of a goblet-cell carcinoid tumor of the appendix which metastasized to the peritoneum and was treated by using cytoreductive surgery (CRS) with intraperitoneal chemotherapy. A 47-year-old male presented with chronic constipation and was diagnosed as having a rectal adenocarcinoma with a signet-ring-cell component under colonoscopy. Computed tomography suggested peritoneal metastases with diffuse nodular parietal peritoneal thickening of the entire abdomen and focal invasion of the upper rectum by a seeding mass. CRS with intraperitoneal chemotherapy was done under the diagnosis of a rectal adenocarcinoma with peritoneal metastases. The pathologic diagnosis was a goblet-cell carcinoid tumor of the appendix with peritoneal metastasis. The histological discrepancy between a peritoneal metastatic mass and a rectal mass was due to the mixed histological pattern of a goblet-cell carcinoid tumor. A metastatic mass may not share identical immunohistochemical characteristics from its origin. This histologic discrepancy necessitates caution in diagnosing a distant metastasis of a goblet-cell carcinoid tumor.