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A 73-year-old woman was referred to our hospital with a chief complaint of black stools and abdominal distention. She was diagnosed with advanced gastric cancer with pyloric stenosis and multiple lymph node metastasis(cT4aN3M0, cStage Ⅲ)and was administered preoperative chemotherapy after laparoscopy and gastric jejunal bypass surgery. The surgical diagnosis was sT4aN3M0P0CY0. After surgery, 2 courses of DS therapy were administered. However, a new liver metastatic lesion was found, and XELOX therapy was selected as the second-line of treatment. Subsequently, enlarged hepatic hilar lymph nodes were found; microsatellite instability testing confirmed MSI-High cancer. Nivolumab was selected as the third- line therapy. After 15 courses, a new liver metastatic lesion appeared. Although Ram+nab-PTX therapy was chosen as the fourth-line therapy, the patient developed myelosuppression after 3 courses. Two years and 4 months after the initial treatment, the patient was considered to have achieved CR. Because drug-induced liver injury had occurred, the Ram therapy was discontinued. The patient has remained in CR for 1 year without receiving any anticancer drugs. This case suggests that for MSI-high patients with gastric cancer, the consideration of treatment strategy should be based on the molecular biological background.

A 79-year-old man was detected with anemia on medical examination and underwent gastroscopy at the previous hospital. Gastroscopy revealed a 15-mm ulcerative lesion(Type 0-Ⅱc plus Ⅲ)on the greater curvature of the upper gastric body. Tumor biopsy showed well-differentiated adenocarcinoma. The patient was suspected of deep submucosal invasion due to poor stretching of the gastric wall and the ulcer depth; hence, he was transferred to our hospital for surgery. When gastroscopy was repeated, the ulcer was found to be scarred(Type 0-Ⅱc), thereby indicating the occurrence of intramucosal carcinoma; hence, endoscopic submucosal dissection was performed. The pathological finding showed 10×6 mm, tub1, pT1a, ly0, v0, pUL1, pHM0, pVM0, suggesting a curative resection. Early gastric cancer of the depressed type is known to develop a malignant cycle with repeated improvements and exacerbations of the ulcer. Diagnosing the depth of tumor invasion is particularly difficult when there is an active ulcer. For small lesions with active ulcers, repeating gastroscopy might allow for correct diagnosis and appropriate treatment.

A 78-year-old man was admitted to our hospital with a diagnosis of esophageal cancer and gastric cancer. Gastroscopy showed a type 2 tumor located in the cardia from the lower esophagus, and a pathological examination showed malignant melanoma. Based on the physical examination and other imaging tests, the patient was diagnosed with primary amelanotic malignant melanoma of the esophagus, but the tumor was unresectable due to extensive lymph node metastasis. According to the guideline, immune checkpoint inhibitor(nivolumab)was used for treatment, but because the tumor progressed after 2 courses and the performance status of the patient worsened, aggressive treatment was ended. Six weeks after finishing treatment, computed tomography showed that the tumor had shrunk to some extent. The patient ultimately died from aspiration pneumonia 4 months after the first consultation. The patient was thought to have had an immune-related adverse event, with the tumor showing pseudoprogression.

Recently, the interest in cancer genomic medicine has increased, owing to the powerful and cost-effective technology of next-generation sequencing(NGS), which allows rapid identification of a large number of gene mutations. TP53 mutations are frequently found in solid cancers, especially in esophageal squamous cell carcinoma(ESCC), wherein the frequency of TP53 mutation is considered to be 90% or more. However, there is no clinical targeted therapy as yet utilizing TP53. Here, we aimed to characterize TP53 mutations associated with ESCC, in order to assess its feasibility as a therapeutic target. We extracted DNA and RNA from specimens of ESCC patients and analyzed them using NGS, which revealed different TP53 mutations. Based on previous reports, it is considered that different TP53 mutations lead to different functions of the protein, and subsequently account for varied prognosis in squamous cell carcinoma of the head and neck. We also performed cell viability assay using ESCC cell lines with different TP53 mutations and 2 kinds of p53-targeted drug and found differences in the growth inhibition of the cell lines. Although individual treatment can be determined depending on the type of TP53 mutation, it would be necessary to further examine the interaction of TP53 with other genes to determine its therapeutic efficacy as a target.

Immunocheckpoint inhibitors including anti-PD-1 antibody have shown certain therapeutic effects on various cancer types. They have also attracted great attention as novel cancer treatment options in addition to surgical resection, chemotherapy, and radiation therapy. Herein, we report a case of gastric cancer that was successfully treated with conversion surgery after nivolumab treatment. The patient was 68 years old and male. Upper gastrointestinal endoscopy revealed a type 3 tumor in the antrum, and he was referred to our department for further examination. The gastric cancer was diagnosed as cT4aN2M0, cStage ⅢA, and he was administered SOX as the first-line and nab-PTX/RAM as the second-line treatment, which was also a PD. As the third-line treatment, nivolumab showed remarkable reduction of the tumor after initiation, and after 14 courses, conversion surgery was performed. The patient remains alive without recurrence.

A 67-year-old female was diagnosed with Stage Ⅳ rectal cancer with paraaortic lymph node metastasis. The patient underwent Hartmann's operation with D3 lymph node and paraaortic lymph node dissection. Postoperative chemotherapy with FOLFIRI was then administered for 1 year. However, liver metastasis developed, for which partial hepatectomy was performed. Postoperative chemotherapy with S-1(20 courses)was then administered. Three years and 11 months following the first operation, lymph node metastases developed and resection of lymph nodes(No. 12p, No. 16b1int)was performed. Postoperative chemotherapy with capecitabine(Cape)(8 courses)was then administered. Five years and 7 months following the first operation, Virchow lymph node metastasis developed. Despite chemotherapy with Cape and bevacizumab (Bmab), Virchow lymph node swelling recurred, and resection was performed. Nine years and 4 months following the first operation, lymph node metastases developed, and resection of lymph nodes(Virchow, No. 16b1int)was performed. Postoperative chemotherapy with S-1(8 courses)was then administered. At present, 11 years and 4 months after the first operation, the patient, whose chemotherapy has been discontinued, is alive without recurrence.

Genome medicine has been attractingmuch of attention in Japan. The combination of molecular targetingdrug s and somatic mutations has been developed for cancer treatment, which was introduced clinically with evidence by cancer type. Several cancer somatic mutations can be identified in a single test inexpensively using next-generation sequencing(NGS). Drug approval not based on organs but on cancer genome analysis has been practiced mainly in the United States, and is also being implemented in Japan. However, cancer treatment strategies using molecular targeting drugs and the associated diagnosis are limited in each type of cancer. Furthermore, the benefit of NGS, which is an improved and inexpensive technique, is still insignificant in Japan. However, the clinical biobank system was initiated in 2011 to prepare the era of cancer genome medicine in our department. The quality of biological samples was strictly controlled by the standardized sampling procedures, which can be used by the researchers accordingto their convenience. Furthermore, the cooperative research involvingcommercial corporations has been started.