[Surgery for metastatic lung tumor from malignant tumor of liver, biliary duct and pancreas].

BACKGROUND: Resection of lung metastasis from malignant tumor of liver, biliary duct and pancreas has various controversial problems. These problems are that many patients have a progressive disease and there are few patients who can have resectable lesion. Generally the prognosis of these diseases is poor. In addition, the effect of pulmonary resection for lung metastasis from malignant tumor of liver, biliary duct and pancreas is unclear. We set out to investigate the outcome and usefulness of surgery in this group. PATIENTS AND METHODS: From January 1999 to November 2012, 18 patients underwent a total of 21 surgeries. There were 11 men and 7 women with mean age of 66.6±10( range, 43 to 78). Primary diseases of these patients were hepatocellular carcinoma in 5, cholangiocellular carcinoma in 1, cholangiocarcinoma in 2 and pancreatic cancer in 10 patients. RESULTS: Disease-free interval from 1st local therapy such as surgical treatment for primary lesion was 50.8±28.7(range, 19 to 107) months. Numbers of lung metastasis were 1 in 15, 2 in 4 patients and 3 in 1 patient. Many metastasis were in right lower lobe. Numbers of wedge resection were 13, segmentectomy were 4, lobectomy were 2 in these patients. Average of total survival time was 38±34 months. Four patients were dead. The 14 patients are alive and 7 patients had no recurrence. Adjuvant therapy such as chemotherapy was important. One-year all over survival rate after 1st pulmonary resection was 88%, 3 or 5-years was 73%. We think that it's was good result. CONCLUSION: There is a possibility that surgery for metastatic lung tumor from malignant tumor of liver, biliary duct and pancreas is useful by control of primary lesion and selecting of patients and adjuvant therapy such as chemotherapy.

Targeting MARCO can lead to enhanced dendritic cell motility and anti-melanoma activity.

We reported that murine tumor lysate-pulsed dendritic cells (TP-DC) could elicit tumor-specific CD4(+) and CD8(+) T cells in vitro and in vivo. In some limited cases, TP-DC treatments in vivo could also result in regression of established subcutaneous tumors and lung metastases. By gene array analysis, we reported a high level of expression of a novel member of the cell surface class A scavenger receptor family, MARCO, by murine TP-DC compared to unpulsed DC. MARCO is thought to play an important role in the immune response by mediating binding and phagocytosis, but also in the formation of lamellipodia-like structures and dendritic processes. We have now examined the biologic and therapeutic implications of MARCO expressed by TP-DC. In vitro exposure of TP-DC to a monoclonal anti-MARCO antibody resulted in a morphologic change of rounding with disappearance of dendritic-like processes. TP-DC remained viable after anti-MARCO antibody treatment; had little, if any, change in production of IL-10, IL-12p70 and TNF-alpha; but demonstrated enhanced migratory capacity in a microchemotaxis assay. The use of a selective inhibitor showed MARCO expression to be linked to the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo, anti-MARCO antibody treated TP-DC showed better trafficking from the skin injection site to lymph node, enhanced generation of tumor-reactive IFN-gamma producing T cells, and improved therapeutic efficacy against B16 melanoma. These results, coupled with our finding that human monocyte-derived DC also express MARCO, could have important implications to human clinical DC vaccine trials.

Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse.

We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity.

Three-dimensional simulation, surgical navigation and thoracoscopic lung resection.

This report describes a 3-dimensional (3-D) video-assisted thoracoscopic lung resection guided by a 3-D video navigation system having a patient-specific 3-D reconstructed pulmonary model obtained by preoperative simulation. A 78-year-old man was found to have a small solitary pulmonary nodule in the left upper lobe in chest computed tomography. By a virtual 3-D pulmonary model the tumor was found to be involved in two subsegments (S1 + 2c and S3a). Complete video-assisted thoracoscopic surgery bi-subsegmentectomy was selected in simulation and was performed with lymph node dissection. A 3-D digital vision system was used for 3-D thoracoscopic performance. Wearing 3-D glasses, the patient's actual reconstructed 3-D model on 3-D liquid-crystal displays was observed, and the 3-D intraoperative field and the picture of 3-D reconstructed pulmonary model were compared.

Complete video-assisted thoracoscopic multi-subsegmentectomy based on patients' specific virtual 3-D pulmonary models.

INTRODUCTION: Video-assisted thoracoscopic surgery is widely used for resecting early-stage non-small cell lung cancer. Segmentectomy and subsegmentectomy require a thorough knowledge of the 3-D bronchovascular anatomy of the lung. Previously, our department reported using a 3-D pulmonary model of a patient for thoracoscopic surgical treatment of non-small cell lung cancer. This study investigates multi-segmentectomy for patients with non-small cell lung cancer. METHODS: Between July 2001 and January 2012, 943 patients underwent surgical resection of primary lung cancer. Of these, 11 patients had video-assisted thoracoscopic multi-subsegmentectomy. For preoperative simulation, virtual 3-D pulmonary models have been constructed since July 2001. RESULTS: The mean age of patients was 69.2 ± 11.6 years (range, 43.0-86.0 years). Histological diagnoses included adenocarcinoma in eight patients, squamous cell carcinoma in two, and large cell carcinoma (neuroendocrine tumor) in one. Tumor size was ≤ 10 mm in one patient, 11-15 mm in four, 16-20 mm in four, and 21-25 mm in two. One patient was treated without lymphadenectomy, nine patients underwent additional hilar lymphadenectomy, and one patient underwent additional hilar and mediastinal lymphadenectomy. No patients were converted to thoracotomy. All patients had a macroscopically negative surgical margin. The pathological stage of patients was IA in nine patients, IB in one, and IIA in one. No pulmonary vessel injuries were found. Three patients had a prolonged lung air leak (> 6 days). CONCLUSION: Using a reconstructed 3-D pulmonary model, this study demonstrates that video-assisted thoracoscopic multiple subsegmentectomy is feasible with adequate margins in selected patients.