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Near-infrared photoimmunotherapy(NIR-PIT)is a novel cancer treatment modality that employs antibody-IRDye700DX (IR700)conjugates. Recently, the clinical application of NIR-PIT has received approval in Japan for patients with inoperable head and neck cancer, specifically targeting the human epidermal growth factor receptor(hEGFR). Furthermore, NIR-PIT extends beyond the scope of tumor antigens and can be employed to eliminate specific host cells that contribute to the creation of immune-permissive environments supporting tumor growth. One of the distinguishing features of NIR-PIT is its ability to selectively eliminate various cell types within the tumor microenvironment(TME)by specifically targeting distinct antigens. By employing podoplanin(PDPN)-targeted NIR-PIT, PDPN-expressing fibroblasts were selectively eradicated, resulting in the suppression of tumor progression and a notable extension of overall survival. Additionally, we investigated the efficacy of depleting myeloid-derived suppressor cells(MDSCs)using NIR-PIT. This approach led to the selective elimination of MDSCs within tumors, and remarkable abscopal effects were observed in bilateral tumor models. Hence, NIR-PIT holds immense promise for the treatment of diverse cancer types by precisely targeting tumor cells, fibroblasts, and immune cells.

Pancreatic ductal adenocarcinoma(PDAC)is lethal malignancy with abundant stroma. Cancer-associated fibroblasts (CAFs) exist in the PDAC stroma and contribute to progression of malignant transformation, treatment resistance, and recurrence. However, effective treatment to control PDAC stroma has not been established. We have developed tumor suppressor gene p53-armed oncolytic adenovirus(OBP-702), and have clarified therapeutic effects on PDAC cells. In this study, we investigate the therapeutic effect of OBP-702 on PDAC CAF.

Development of immunotherapy, especially checkpoint inhibitors, dramatically improved the prognosis of some malignancies. However, problems on the occurrence of severe adverse effects and limited responses to these checkpoint inhibitors remain. Recently, tumor infiltrating lymphocytes(TILs)are the predictive markers of immunotherapies based on clinical evidence. The proportion of cytotoxic T cells in the tumor has been reported to affect the antitumor effect. TILs in the tumor are thought to be controlled by the interaction between cancer and tumor microenvironment. As a cause of tumor immunosuppression, cancer-associated fibroblasts(CAFs)play the main role in the tumor microenvironment. We considered the strong involvement of tumor microenvironment, particularly the role of CAFs, and reported the interaction between CAFs and proliferation, invasion, angiogenesis, and resistance in the conventional therapy. The correlation between CAFs and tumor immunity and the immunosuppression promoted by CAFs were also evaluated. Their effects will be reported in our future studies.

We report a case of an elderly patient with advanced esophageal cancer who underwent multidisciplinary treatment. An 86-year-old male consulted our hospital with complaints of pharynx discomfort and difficulty in swallowing. He was preoperatively diagnosed with esophageal cancer, T3N2M0, Stage III . We performed 2 courses of cisplatin plus 5-FU therapy as neoadjuvant chemotherapy. The primary tumor and metastatic lymph nodes reduced in size, and thoracoscopic esophagectomy in the prone position was performed. Pathological findings were esophageal cancer, pT3-Ad, INF b, ly2, v1, IM0, pPM0, pDM0, pRM1, pN3, pStage III . As the radical margin was positive, chemoradiotherapy was performed. We continued postoperative chemotherapy for approximately 1 year, and the patient has survived without relapse for 4 years from esophagectomy. Even in patients over 80 years old, long-term prognosis can be expected by performing radical surgery and chemoradiotherapy.

The esophagorespiratory fistula(ERF)is a fatal complication ofesophageal cancer, because ofadvanced oncological status and poor conditions due to pneumonia and/or malnutrition.We report here a case of patient who was successfully treated for esophageal cancer with ERF with multimodality therapy including three-stage operation. A 65-year-old woman ofesophageal cancer received preoperative chemotherapy, and developed EFR before operation. Prolonged conservative therapies for ERF let her general condition get worse. Therefore, the patient underwent esophagostomy and gastrostomy to recover her condition. She received chemo-radiotherapy followed by esophagectomy. And she was performed the reconstruction next month. She is still alive without recurrence at 20 months after resection. In previous reports, a total of 6 cases have been performed esophagectomy for esophageal cancer with ERF in Japan. Only one case was reported that had survived longer than 12 months. This multimodality therapy can be one ofthe best strategies for the patients ofesophageal cancer with ERF, even ifthey have poor condition.

Advances in molecular and cellular biochemistry, such as the development of targeted cancer therapy, have dramatically improved the prognosis of cancer patients. Emerging data have suggested that bevacizumab treatment may act by controlling the cancer microenvironment. Many reports have examined the interaction of cancer cells with the tumor microenvironment, and cancer-associated fibroblasts (CAFs) are thought to play a central role in this process. We speculated that the cancer microenvironment and in particular, CAFs, strongly influence the development of esophageal cancer. We have analyzed the signaling pathways of molecular targets. However, inhibition of a single signaling pathway is insufficient to treat cancer effectively. Photoimmunotherapy is a molecular-targeted specific cancer therapy using near-infrared radiation, which was introduced by Mitsunaga et al. in 2011. We are using its specific method of killing cells to target CAFs. We will report the results of its effect on cancer cells in the future.

Since reported in the JCOG9907 trial, neoadjuvant chemotherapy prior to surgery has become the standard treatment for advanced (Stage II/III) esophageal cancers. However, more powerful neoadjuvant chemotherapy is required for the treatment of locally advanced cases or cases involving multiple lymph node metastases. At our institute, DCF therapy (docetaxel, cisplatin, and 5-fluorouracil) is administered selectively for the treatment of patients with far-advanced esophageal cancer. We treated 53 thoracic esophageal cancer patients who underwent surgery following neoadjuvant chemotherapy between January 2010 and December 2012. FP therapy (cisplatin and 5-fluorouracil) was administered to 43 patients, and DCF therapy to 7 patients who had far-advanced esophageal cancer. All patients treated with DCF therapy experienced grade 3 and 4 adverse events. With the exception of 1 patient, all patients who received DCF therapy could undergo curative surgery. DCF therapy could become an effective preoperative chemotherapy.

In our institute, we introduced PET-CT examination as the preoperative and postoperative screening for esophageal cancer patients in April 2006. During two years before the introduction of PET-CT examination, we performed an intensive local control therapy (operation, RFA, definitive chemoradiotherapy) to 13 cases with single region recurrence (including 5 cases of cervical lymph nodes recurrence, 5 of local recurrence, 3 of distant metastatic recurrence). On the other hand, we performed an intensive local control therapy to 21 cases (including 4 cases of cervical lymph nodes recurrence, 10 of local recurrence, and 7 of distant metastatic recurrence) during two years after the introduction of PET-CT examination. In any pattern, there was a tendency of improvement in the prognosis of recurrent esophageal cancer patients. These results raised the possibility that PET-CT examination was useful for an early detection of the recurrent lesions in postoperative follow-up for esophageal cancer patients. And there might be a chance of curability in patients with single region recurrence by the early detection.

We report a case of a woman in her sixties having primary duodenal carcinoma with multiple liver metastases who was treated with oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 2 courses of the chemotherapy, computed tomography showed a partial response without any severe adverse events. Now at 8 months, the PR stage has been maintained. So far, no standard therapeutic strategy for metastatic duodenal carcinoma has been developed. However, we suggest a FOLFOX regimen can be highly effective as a safe approach for continuously maintaining the quality of life of patients with this rare type of cancer.