A Japanese woman in her 50s presented with coffee-ground vomiting at a local clinic and was referred to our hospital for further investigation. Esophagogastroduodenoscopy demonstrated a submucosal tumor in the descending part of the duodenum, and she was diagnosed with a gastrointestinal stromal tumor (GIST) by other imaging studies. Elective surgery of the tumor was initially planned. However, on the 13th day of hospitalization, emergency pancreaticoduodenectomy was performed because of massive hematemesis with hemorrhagic shock. Genetic analysis demonstrated a deletion in exon 11 of the c-kit gene, which could dramatically alter the clinical course. Although duodenal GIST with active bleeding is comparatively rare, we have to assume that it is the cause of gastrointestinal bleeding and treat such cases with a minimally invasive surgical procedure and neoadjuvant/adjuvant chemotherapy. It is necessary to accumulate more cases with duodenal GIST to establish an evidence-based therapeutic strategy.

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia. Various epigenetic regulators are mutated in MDS patients, indicating that accumulation of epigenetic alterations together with genetic alterations plays a crucial role in the development of MDS.

Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC). The host genetic factors involved in the development of HCC in patients with HCV infection were investigated. To identify the genetic susceptibility factors for HCV-induced HCC, genome wide association studies (GWAS) were conducted in HCV-induced HCC cases and controls of Japanese origin. Single nucleotide polymorphisms (SNPs) which showed possible association in the GWAS were further genotyped using different cohorts. By these analyses, MICA and DEPDC5 SNPs were found to be strongly associated with HCV-induced HCC. These results highlight the importance of MICA and DEPDC5 genetic variations not only as predictive biomarkers for HCV-induced HCC but also as therapeutic targets against hepatocarcinogenesis or HCC.

An 85-year-old man was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma of the colon in 20XX. Although Helicobacter pylori eradication was performed as part of the treatment, it was ineffective. He was followed-up by colonoscopy for 4 years without additional treatment and there was no interval change;however, he was lost to follow-up 6 years after the first visit. Nine years after the initial diagnosis, he presented with new MALT lymphoma lesions in the stomach and small intestine. Genetic analysis showed that a biopsy specimen was positive for API2/MALT1 fusion gene, and IgH rearrangement showed monoclonal banding between colon and stomach. This suggested disseminated monoclonal API2/MALT1-positive MALT lymphoma of the colon, stomach, and small intestine. Careful attention should be paid to the appearance of multiple lesions in MALT lymphoma.

A 72-year-old female was diagnosed with chronic phase chronic myeloid leukemia (CML) in 2001. After a short course of treatment with hydroxycarbamide, imatinib (IM) 400 mg was started. A major molecular response was presumably acquired 10 months later. IM was discontinued after treatment for 47 months in November 2005. At the same time, BCR-ABL transcript was undetectable by nested RT-PCR assay, which was equivalent to <0.00138% BCR-ABL according to the international scale. The patient is still under observation with no additional therapy, and BCR-ABL has remained negative for 102 months, to date. Furthermore, interferon was never used in this patient. IM has dramatically improved the prognosis of CML. Since no cure has yet been established, patients are recommended to continue treatment even after achieving deep molecular responses. There are several ongoing clinical trials challenging the discontinuation of IM, but long-term observation is still lacking. The sustained deep molecular response, exceeding eight years, experienced in this patient is potentially encouraging.

We performed a retrospective study on the use of cetuximab or panitumumab alone in patients with KRAS wild-type metastatic colorectal cancer between November 2008 and February 2012. Twenty-two patients were analyzed and classified as PS 0/1 (good PS group)and PS 2/3/4 (poor PS group)with 11 patients in each group. The response rate, disease control rate, median progression-free survival, and median overall survival were 9%, 73%, 5.1 months (95%confidence interval[CI]: 1.5-8.7), and 16 months (95% CI: 8.8-24), respectively, in the good PS group, and the corresponding values in the poor PS group were 0%, 18%, 0.7 months (95% CI: 0.3-1.0), and 1.5 months (95% CI: 0.7-2.4). Grade 3 or 4 adverse events were skin toxicities (2 patients with grade 3 toxicities), panitumumab-related interstitial lung disease (1 patient with grade 4 toxicity), and cetuximab infusion-related reaction (1 patient with grade 4 toxicity). No treatment-related deaths were observed. In conclusion, the efficacy and safety of cetuximab or panitumumab monotherapy in patients with a good PS in our study were similar to those reported in previous clinical trials, whereas patients with a poor PS showed poorer outcomes.

The patient was a man in his 60s with a history of 2 operations for the treatment of malignant neurogenic tumors. Partial resection of the stomach and liver was performed in December 2006, followed by chemotherapy with adriamycin and interferon; resection of a recurrent tumor in the left subphrenic space was performed in December 2007. In June 2011, recurrent tumors were detected in the lesser curvature of the stomach body and left inferior quadrant of the abdomen (12 mm [SUVmax 7.9] and 23 mm [SUVmax 10.5], respectively)by using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). The tumors resected in August 2011 were diagnosed as malignant peritoneal mesothelioma on immunohistochemical analysis. In February 2013, FDG-PETrevealed a 20-mm tumor of in the mesentery with a SUVmax of 7.6, and the tumor was resected. This secondary tumor had the same features of the previously resected malignant mesothelioma. Fluorescence in situ hybridization revealed no deletion of the p16 gene, and the patient had had no other recurrence during follow-up. Malignant peritoneal mesothelioma is a rare disease, accounting for 10% of all malignant mesothelioma cases, with low rates of p16 gene deletion compared with malignant pleural mesothelioma. Previous studies have reported that the lack of p16 deletion is associated with better prognosis in malignant pleural mesothelioma. Herein, we report of a patient diagnosed with malignant peritoneal mesothelioma, without deletion of the p16 gene, who survived for over 2 years and 10 months after initial diagnosis of malignant mesothelioma.

Lynch syndrome is an inherited autosomal dominant disorder caused by germ-line mutation of mismatch repair genes, in which a malignant tumor develops at a young age in the colon, endometrium, stomach, or other tissues. A 54-year-old patient with gastric cancer received pylorus-preserving gastrectomy, and a genetic examination confirmed a pathological variation of the MLH1 gene. Five years after surgery, an upper gastrointestinal endoscopy revealed a residual 0 -IIa+IIc gastric tumor approximately 2 cm in size extending from the anastomotic site to the lesser curvature side of the stomach. The remaining stomach was completely removed. The final diagnosis was T1b (SM) N1M0, StageIB gastric cancer. Microsatellite instability was positive, and we attributed the cancer to Lynch syndrome. In Lynch syndrome, the risk of multicentric gastric cancer is higher than normal, and for the initial therapy, preventive total gastrectomy should be considered as an option.

Since 1994, a Phase I/II clinical study and radiotherapy have carried out using carbon-ion beams produced with the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences. Now we constructed the new treatment facility for the advanced carbon-ion therapy at HIMAC applying a 3D fast spot scanning system with pencil beams. In the field of fundamental biological studies for high-LET heavy ions, there are some reports regarding bystander effects after exposure to alpha particles derived from 238Pu or He-ion microbeams. However, only limited sets of studies have examined bystander effects after exposure to different ion species heavier than helium, such as carbon ions. We have been investigating bystander cellular responses in both normal human and human tumor cells irradiated with the HIMAC carbon ions. Bystander cell-killing effect was observed in the cells harboring wild-type P53 gene, but not in the P53-mutated cells. Moreover, observed bystander effect was suppressed by treating with a specific inhibitor of gap-junction mediated cell-cell communication. There is clear evidence that the carbon-ion irradiation enables the enhanced cell killing in cells with wild-type P53 gene via gap-junction mediated bystander effect.