[A Case of Curative Resection of the Local Advanced Gastric Cancer after SOX plus Nivolumab Chemotherapy, and the Pathological Diagnosis Was Complete Response].

A-78-year-old woman presented with difficulty swallowing. She was diagnosed as having advanced upper gastric cancer with invasion to the esophagus and the diaphragm. Biopsy examination of the tumor showed MSI-high and HER2-negative. The patient received 4 courses of SOX plus nivolumab in combination. After the chemotherapy, the size of the tumor decreased remarkably. We performed total gastrectomy with D2 lymph node dissection. Pathological examination revealed no residual cancer at the primary tumor location and the regional lymph nodes. The patient has shown no recurrence for 9 months without adjuvant chemotherapy. We conclude that SOX plus nivolumab in combination as first-line chemotherapy is an effective strategy against advanced gastric cancer.

[Clinical Features and Treatment for Cholangiolocellular Carcinoma(CoCC)-Report of Three Cases].

We report 3 cases of cholangiolocellular carcinoma(CoCC)experienced from April 2017 to March 2021 in our hospital. The average age of the cases is 74.3 years old, 2 males and 1 female respectively. Hepatectomy was performed in 2 cases, and transcatheter arterial embolization(TAE)and radiofrequency ablation(RFA)therapy was performed in 1 case because of old age and his wishes as the background liver disease. Chronic hepatitis C was found in 1 case, fatty liver in 1 case, and alcoholic liver disease in 1 case. Two patients who underwent hepatectomy had good long-term prognosis, but another patient who underwent TAE and RFA developed early recurrence at bone and died in 3 months after treatment. Therefore, we consider that the risk of recurrence should be examined and the treatment should be performed accordingly.

Efficacy of 5-aminolevulinic acid-mediated photodynamic therapy in a mouse model of esophageal cancer.

5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a minimally invasive therapeutic modality used in the management of various cancers, but to a lesser extent for esophageal cancer (EC). The current study investigated the antitumor effects of ALA-PDT. Human EC cells were treated with ALA, after which ALA-induced fluorescence was examined under a fluorescence microscope. The cytotoxic effects of ALA-PDT were assessed using three types of LEDs (blue, green and red) in vitro and in vivo. Subcutaneous tumor model mice was constructed with KYSE150 cells. ALA-PDT was performed once a week for 4 weeks and tumor weights were measured. A popliteal lymph node (PLN) metastasis murine model was generated using KYSE150 cells. KYSE150 cells were inoculated into the left footpad of nude mice. ALA-PDT was performed on the footpad once a week for 4 weeks. PLNs were then removed 3 weeks after the last treatment. The lymph nodes were evaluated by hematoxylin and eosin staining. Red fluorescence of protoporphyrin IX (PpIX) was observed in all EC cell lines. ALA-PDT using LEDs exerted significant antitumor effects in vitro and in vivo. The antitumor effects of ALA-PDT with blue LED were the strongest, followed by green and red LEDs. The number of metastasized PLNs was significantly smaller in the ALA-PDT group (0%) than in the control group (37.5%). The present results indicated that ALA-PDT is effective for EC.

[Case of a 5mm Rectal Neuroendocrine Tumor(G1)with Lymph Node Metastasis].

Screening colorectal endoscopy revealed a 5mm rectal neuroendocrine tumor(NET: G1)in a 72-year-old man. Endoscopic mucosal resection(EMR)was performed, and the histopathological examination demonstrated lymphatic and vessel invasion with a possible positive vertical margin. Therefore, we performed laparoscopic low anterior resection, lymphadenectomy, and ileostomy as additional surgical resections. No residual tumor was found in the specimen, but 3 metastatic lymph nodes were identified. The rate of lymph node metastasis in rectal NETs of diameter<10mm is low, and additional surgery can reduce the patient's quality of life affected due to impaired anorectal function. However, in the Japanese guidelines for NET, additional surgery is adopted in cases with high-risk factors for lymph node metastasis. Therefore, it is necessary to select between additional surgery and careful follow-upfor rectal NETs of diameter<10mm with high-risk factors because of possible lymph node metastasis.

[Curative Resection of Advanced Rectal Cancer with Direct Invasion of the Prostate and Extra-Regional Lymph Node Metastases after Chemotherapy].

A-69-year-old man presented with an obstructed defecation. He was diagnosed as having advanced lower rectal cancer with direct invasion of the prostate and metastases to regional and para-aortic lymph nodes. Biopsy examination of the tumor showed RAS wild-type expression and negative BRAF V600E mutation. The patient received 13 courses of mFOLFOX6 and panitumumab(Pmab)in combination and 1 course of mFOLFOX6 alone. After the chemotherapy, the size of the primary tumor and lymph node metastases decreased remarkably. 18F-fluorodeoxyglucose-positron emission tomography(18F-FDG- PET)showed no 18F-FDG accumulation in the tumor and lymph nodes. We performed laparoscopic abdominoperineal resection with D3LD2 lymph node dissection and left external iliac lymph node(293-lt)sampling. Pathological examination revealed no residual cancer at the primary tumor location and only a few malignant cells remained in the 293-lt lymph node. The patient has shown no recurrence for 1 year without adjuvant chemotherapy. We conclude that mFOLFOX6 and Pmab in combination is an effective preoperative chemotherapy against advanced RAS wild-type rectal cancer. This strategy may reduce surgical invasion and save the surrounding organs while maintaining curability.

Photodynamic diagnosis of peritoneal metastasis in human pancreatic cancer using 5-aminolevulinic acid during staging laparoscopy.

Peritoneal metastasis is an important prognostic factor for pancreatic cancer. The present study evaluated the possibility of diagnosing peritoneal metastasis by a photodynamic diagnosis using 5-aminolevulinic acid (5-ALA-PDD). In vitro, protoporphyrin IX (PpIX) accumulation was examined in the AsPC-1-GFP cell line following 5-ALA hydrochloride administration. In vivo, AsPC-1-GFP cells were injected into the peritoneal cavities of mice. Three weeks later 5-ALA hydrochloride was intraperitoneally administered to the mice. The peritoneal nodules were observed under fluorescence excitation. A total of 34 patients were enrolled in the present study who were clinically diagnosed with pancreatic malignancy. 5-ALA hydrochloride was orally administered to the patients prior to surgery. During the operation the abdominal cavity was observed under white light and fluorescence. In vitro and in vivo, it was confirmed that PpIX-induced red fluorescence. In 9 patients peritoneal nodules suspected to be peritoneal metastasis were observed under white light. In 4 of the 9 patients nodules were detected on the basis of the fluorescence images. Fluorescent nodules were histopathologically diagnosed as metastatic. In the present study it was confirmed that 5-ALA-PDD holds promise for the rapid diagnosis of peritoneal metastasis in patients with pancreatic cancer.

Photodynamic Diagnosis of Hepatocellular Carcinoma Using 5-Aminolevulinic Acid.

UNLABELLED: Backgtound/Aim: Since hepatocellular carcinoma (HCC) has a high recurrence rate, accurate diagnosis of its location and curative resection is important to improve survival. This study evaluated the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) for HCC. MATERIALS AND METHODS: We used two human hepatoma cell lines (HuH-7 and Hep G2). Cells were treated with 5-ALA for 4 h. 5-ALA-induced fluorescence was then examined under a fluorescence microscope. We designed hepatoma mouse models, with mice receiving an intraperitoneal injection of 5-ALA. After 4 h, their liver tumors were removed and examined under a fluorescence microscope. We also analyzed 12 HCC patients who underwent curative liver resection. The patients were administered 5-ALA orally before surgery. The excised livers were sectioned and examined by fluorescence microscopy. RESULTS: In vitro and in vivo, red fluorescence of protoporphyrin IX (PpIX) was observed in tumors. In 11 of 12 patients, red fluorescence was observed in their HCC. The tumor of only one patient did not exhibit red fluorescence because it had been necrosed by transcatheter arterial chemoembolization (TACE). CONCLUSION: Red fluorescence of PpIX was observed in hepatoma cells, tumors of HCC mouse models and HCC of patients. PDD of HCC using 5-ALA is simple and may be useful for real-time diagnosis during liver resection.

The first case of POEMS syndrome with synchronous breast cancer: What are the associated diagnostic challenges?

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes (POEMS) syndrome is a rare plasma cell disorder that causes a paraneoplastic syndrome. We report the first case of POEMS syndrome with synchronous breast cancer. The patient was at risk of being misdiagnosed with metastatic cancer, and it is important to emphasize that physical examinations provided vital diagnostic clues.

Primary rectal diffuse large B-cell lymphoma associated with ulcerative colitis: a case report.

We need to be aware of primary intestinal lymphoproliferative disease (PILD) associated with ulcerative colitis (UC). We should carefully monitor UC patients, particularly patients who meet the following conditions; a previous Epstein-Barr virus infection, treatment duration ≧4 years, male, and age ≧50 years.

[Radiosensitizing effect of 5-aminolevulinic acid (5-ALA ) in Colon cancer].

5-aminolevulinic acid (5-ALA) is widely used in clinical practice because it shows tumor-selective accumulation of protoporphyrin IX, a fluorescent substance and a metabolite of 5-ALA. In addition, some studies have reported that 5-ALA increases the radiation sensitivity of glioma and melanoma. In this study, we investigated the radiosensitization effect of 5-ALA on colon cancer. Mice implanted with the human colon cancer cell line HT29 were administered 5-ALA and subsequently X-ray irradiated. These mice were compared with those not administered 5-ALA. Following multiple irradiations, the tumor volume of the 5-ALA group was significantly lower than that of the non-5-ALA group (day 5: p value=0.0489, day 8: p value= 0.0318, day 12: p value=0.0394). Tumor growth was inhibited by multiple irradiations in the 5-ALA group compared with the non-5-ALA group. These results suggest that 5-ALA also exhibits a radiosensitization effect on colon cancer.

Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice.

Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those that received allogeneic WT splenocytes. Donor CD8(+) T cells deficient in DNAM-1 showed significantly less proliferation and infiltration of the liver and intestines of recipient mice and produced less IFN-γ after coculture with allogeneic splenocytes than WT CD8(+) T cells. Mice prophylactically treated with an anti-DNAM-1 antibody showed milder GVHD and lower mortality than those treated with a control antibody. Moreover, treatment with a single administration of the antibody after the overt onset of GVHD ameliorated GVHD and prolonged survival. Finally, we show that the anti-DNAM-1 antibody therapy also ameliorated the overt GVHD in lethally irradiated mice after MHC-matched, minor antigen-mismatched bone marrow transplantation. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD.