Real-time 4-D radiotherapy for lung cancer.

Respiratory motion considerably influences dose distribution, and thus clinical outcomes in radiotherapy for lung cancer. Breath holding, breath coaching, respiratory gating with external surrogates, and mathematical predicting models all have inevitable uncertainty due to the unpredictable variations of internal tumor motion. The amplitude of the same tumor can vary with standard deviations > 5 mm occurring in 23% of T1-2N0M0 non-small cell lung cancers. Residual motion varied 1-6 mm (95th percentile) for the 40% duty cycle of respiratory gating with external surrogates. The 4-D computed tomography is vulnerable to problems relating to the external surrogates. Real-time 4-D radiotherapy (4DRT), where the temporal changes in anatomy during the delivery of radiotherapy are explicitly considered in real time, is emerging as a new method to reduce these known sources of uncertainty. Fluoroscopic, real-time tumor-tracking technology using internal fiducial markers near the tumor has ± 2 mm accuracy, and has achieved promising clinical results when used with X-ray therapy. Instantaneous irradiation based on real-time verification of internal fiducial markers is considered the minimal requisite for real-time 4DRT of lung cancers at present. Real-time tracking radiotherapy using gamma rays from positron emitters in tumors is in the preclinical research stage, but has been successful in experiments in small animals. Real-time tumor tracking via spot-scanning proton beam therapy has the capability to cure large lung cancers in motion, and is expected to be the next-generation real-time 4DRT.

Study on the Effects of Different Cutting Angles on the End-Milling of Wire and Arc Additive Manufacturing Inconel 718 Workpieces.

This research presents an analysis of the effects of different cutting angles on the side milling of Inconel 718 products manufactured with the Wire and Arc Additive Manufacturing (WAAM) technique. Considering that this manufacturing technology can build near-net shape products, its surface quality is deemed unqualified as a final product, requiring a post-processing step. In this paper, three different angles-0°, 35°, and 90-are compared, looking for possible differences regarding its machinability. As the alloy in question is a material known for being difficult to machine, and the samples were produced with the additive manufacturing technique that created peculiar characteristics, it was deemed necessary to analyze different aspects of the machining process: the surface quality, tool wear, and cutting forces for all three cases, and to rank the angles regarding these results. With analog experiments with the same alloy but cold-rolled, it was possible to infer that not only is the 0-degree angle is the best option for milling, but the anisotropy of the WAAM samples could be the major source of the differences in the milling results.

Aspergillus nidulans ChiA is a glycosylphosphatidylinositol (GPI)-anchored chitinase specifically localized at polarized growth sites.

It is believed that chitinases play important physiological roles in filamentous fungi since chitin is one of the major cell wall components in these organisms. In this paper we investigated a chitinase gene, chiA, of Aspergillus nidulans and found that the gene product of chiA consists of a signal sequence, a region including chitinase consensus motifs, a Ser/Thr/Pro-rich region and a glycosylphosphatidylinositol (GPI)-anchor attachment motif. Phosphatidylinositol-specific phospholipase C treatment of the fusion protein of ChiA and enhanced green fluorescent protein (EGFP)-ChiA-EGFP-caused a change in its hydrophobicity, indicating that ChiA is a GPI-anchored protein. ChiA-EGFP localized at the germ tubes of conidia, at hyphal branching sites and hyphal tips. chiA expression was specifically high during conidia germination and in the marginal growth regions of colonies. These results suggest that ChiA functions as a GPI-anchored chitinase at the sites where cell wall remodeling and/or cell wall maturation actively take place.

Intrahepatic cholangiocellular carcinoma and hepatocellular carcinoma developed after a 6-year sustained virological response to interferon therapy for chronic hepatitis C.

A 67-year-old male patient presenting with chronic hepatitis C (CHC) achieved a sustained virological response (SVR) following 6 months of treatment with 6 million units of beta-interferon (IFN). The SVR state continued for 6 years. Hepatocellular carcinoma (HCC) developed in liver segments 4 and 5, and was treated with transcatheter arterial chemoembolization, followed by radiofrequency ablation of the tumors. A recurrence of HCC occurred in segment 4 one and a half years after the initial treatment for HCC and a new tumor also developed in segment 8. These tumors were diagnosed to be recurrent HCC, and the three hepatic segments were resected. The pathological examination and immunostaining of the tumors revealed the tumor in segment 4 to be a well to moderately differentiated typical HCC. On the other hand, the tumor in segment 8 was a moderately to poorly differentiated adenocarcinoma and was diagnosed as an intrahepatic cholangiocellular carcinoma (ICC). HCC developed from CHC in a patient who achieved a 6-year SVR after IFN therapy, followed one and a half years later by the development of a heterochronous ICC at a different site, thus indicating the presence of HCC-ICC double cancer. This was an exceedingly rare and clinically important case in terms of the carcinogenic mechanism of HCC and ICC from a post-SVR CHC patient. We have to be aware of the possible development not only of HCC but of ICC after SVR in CHC patients.

Pringle's maneuver and selective inflow occlusion in living donor liver hepatectomy.

While inflow occlusion techniques such as Pringle's maneuver are accepted methods of reducing bleeding without inducing liver injury during liver surgery, donor hepatectomy for living donor liver transplantation is currently performed without inflow occlusion for fear that injury to the graft may result. We have performed donor hepatectomy for 12 years using selective intermittent inflow occlusion, a technique in which the portion used to form the graft is perfused during hepatectomy. Starting in November 2000, we applied intermittent Pringle's maneuver to donor hepatectomy in 81 cases of living donor liver transplantation. We reviewed our experience with Pringle's maneuver and selective inflow occlusion techniques in donor hepatectomy in living donor liver transplantation. The quality of the grafts was assessed and compared by determining maximum postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values. Neither primary nonfunction nor dysfunction occurred. Maximum AST values in the recipients were the same whether the liver segments that formed the grafts were totally ischemic during dissection (total ischemia), partially ischemic (partial ischemia), perfused only with arterial blood flow (portal ischemia), or not ischemic at all (no ischemia). Maximum ALT values in the recipients of the total ischemia group was lower, albeit not significantly, than in other groups. Total inflow occlusion can be applied to living donor hepatectomy without causing graft injury. In conclusion, because the transection surface is blood-free, there is decreased risk to the donor during living donor liver transplantation surgery, and surgeons should not hesitate to apply this technique because it contributes to donor safety.

Pringle's manoeuvre in living donors.

The safety of the donor is paramount in living donor liver transplantation. The most important risk to the donor during hepatectomy is bleeding, and the inflow occlusion technique (Pringle's manoeuvre) has been reported to decrease bleeding without inducing liver injury in liver surgery. However, most transplant centres are doing donor hepatectomies without this technique for fear that it would result in ischaemic injury to the graft. We have done 46 living donor hepatectomies with Pringle's manoeuvre without any negative outcome on the quality of the graft. Surgeons should not hesitate to apply this technique in living donor hepatectomy.