Radiofrequency ablation of pulmonary tumors and normal lung tissue in swine and rabbits

OBJECTIVE: The purpose of the present study was to examine the following during radiofrequency ablation (RFA): (1) the risk of hemorrhage from intrapulmonary large vessels; (2) the risk of incomplete ablation of pulmonary tumors; and (3) the late effect on lung tissue. MATERIALS AND METHODS: A 17-gauge, cool-tip-type radiofrequency electrode was used. The damage to the vessels and bronchi was examined by the injection of a colored silicone rubber, a liquid compound that hardens after injection. To examine the risk of hemorrhage from intrapulmonary large vessels, RFA was conducted at eight sites near the central pulmonary vessels in two swine. To examine the risk of an incomplete ablation for pulmonary tumors, 10 pulmonary nodules were made from a gelatin mixture in another two swine and were treated by RFA. To examine the late effect on lung tissue, RFA was conducted on the peripheral lung in 10 rabbits, and then the ablated regions were examined on days 1, 7, 14, 21, and 28 after RFA. RESULTS: The use of colored silicone rubber enabled us to examine the intrapulmonary vessels and bronchi for opening and leakage. RFA did not damage the large intrapulmonary vessels, even when they were located within the ablated regions. Lung tissue surrounding the gelatin nodules was hardly ablated over its entire circumference. Six of 10 gelatin nodules (60%) showed nonablated areas on the peripheral edges of the nodules. From 21 days after RFA, the ablated rabbit lung formed noninfectious cavities by communicating with the surrounding bronchi. CONCLUSION: It was improbable for hemorrhage to occur even when RFA was conducted near the large intrapulmonary large vessels. Because an incomplete ablation that left tumor cells at the site of ablation could occur during surgery due to the difficulty of ablating the entire tumor circumference, CT scan-guided RFA would be preferable to a surgical approach for making a safe margin. Cavity formation can occur beginning 21 days after RFA, which should be carefully followed up in a clinical setting to identify infection, especially in immunocompromised patients.     

Quantitative analysis of β1,6GlcNAc-branched N-glycans on β4 integrin in cutaneous squamous cell carcinoma

α6β4 integrin plays pivotal roles in cancer progression in several types of cancers. Our previous study using N-glycan-manipulated cell lines demonstrated that defects in N-glycans or decreased β1,6GlcNAc-branched N-glycans on β4 integrin suppress β4 integrin-mediated cancer cell adhesion, migration, invasion, and tumorigenesis. Furthermore, immunohistochemical analysis has shown that colocalization of β1,6GlcNAc-branched N-glycans with β4 integrin was observed in cutaneous squamous cell carcinoma (SCC) tissue. However, until now there has been no direct evidence that β1,6GlcNAc-branched N-glycans are upregulated on β4 integrin in cutaneous SCC. In the present study, we performed an ELISA analysis of β1,6GlcNAc-branched N-glycans on β4 integrins as well as β4 integrins in cell lysates from human normal skin and cutaneous SCC tissues. The SCC samples showed a 4.9- to 7.4-fold increase in the ratio of β1,6GlcNAc-branched N-glycans to β4 integrin compared with normal skin samples. These findings suggest that the addition of β1,6GlcNAc-branched N-glycans onto β4 integrin was markedly elevated in cutaneous SCC tissue compared to normal skin tissue. The value of β1,6GlcNAc-branched N-glycans on β4 integrin may be useful as a diagnostic marker associated with cutaneous SCC tumor progression.     

Podoplanin expression in the cyst wall correlates with the progression of intraductal papillary mucinous neoplasm

A thickened, enhanced cyst wall on imaging examinations is one of the “worrisome features” described in the consensus guidelines for management of intraductal papillary mucinous neoplasm of the pancreas (IPMN). Podoplanin (PDPN) expression by cancer-associated fibroblasts is known to be an indicator of poor prognosis in some types of cancer. We performed immunohistochemical staining for alpha-smooth muscle actin (α-SMA) in IPMN lesions and determined the pathological wall thickness by measuring the thinnest and thickest α-SMA-positive parts of the wall of the largest cyst in each case, and the mean of these two values was recorded as the wall thickness. The thickness of the pathological wall increased with progression from IPMN with low-grade dysplasia to IPMN with an invasive carcinoma. The pathological wall was thicker in IPMN with main duct involvement, nongastric-type IPMN, and IPMN with mural nodules. We also stained for PDPN and assessed the thickness of cyst wall staining as for α-SMA. The thickness of the PDPN-positive cyst wall varied in a pattern similar to the thickness of the α-SMA-positive pathological cyst wall. PDPN-positive stromal fibroblasts in the invasive component of IPMN-IC were evaluated as a ratio to α-SMA-positive fibroblasts. A high ratio (>50 %) of PDPN-positive stromal fibroblasts was a predictor of poor outcome. PDPN expression in the cyst wall correlates with the progression of IPMN. PDPN may be a significant prognostic marker of IPMN-IC.     

A novel de novo point mutation of the OCT‐binding site in the IGF2/H19‐imprinting control region in a Beckwith–Wiedemann syndrome patient

The IGF2/H19‐imprinting control region (ICR1) functions as an insulator to methylation‐sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin‐specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith–Wiedemann syndrome (BWS) or Silver–Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF‐binding site, but also point mutations and a small deletion of the OCT‐binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT‐binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT‐binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT‐binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.     

Tips and tricks of surgical technique for pancreatic cancer: portal vein resection and reconstruction (with videos)

Surgical resection is the only hope for cure in patients with pancreatic cancer. To improve the resectability and achieve better prognosis of this lethal disease, extended resection for pancreatic cancer has been applied. We have performed portal vein resection aggressively for pancreatic cancer with portal vein invasion. We also established a method of portal vein reconstruction using the left renal vein graft for tumors widely extended to the portal vein. Our data show similar survival between patients with portal vein obstruction and those without invasion. We also show that portal vein reconstruction using the left renal vein graft can be performed safely without severe liver damage. With video, we introduce our surgical technique for portal vein resection and reconstruction, especially focusing on the usage of the left renal vein graft, providing several tips for a safe and successful procedure.