素輪 善弘

A defect of the central upper lip vermillion generally requires "like for like" reconstruction because this part of the upper lip can attract attention and has a unique structure and color. In this article, we report use of a labial artery-based horizontal long cross-lip flap for central upper lip vermillion reconstruction. In the first stage of surgery, a horizontal long vermillion flap from the lower lip starting at the left commissure with a vascular pedicle containing an inferior labial artery was raised and transposed to the upper vermillion defect. In the second stage, 12 days later, the pedicle was divided to complete the reconstruction. There were no postoperative complications in articulation or eating, and the patient was satisfied with the esthetic outcome. This surgical technique reduces microstomia and inconvenience in eating and speaking compared with a common horizontal cross-lip flap and provides better color- and texture-matched tissue compared to reconstruction using a tongue flap or mucosal flap. The technique is simple, requires a relatively short surgical time, has minimum donor-site morbidity and permits good esthetic and functional reconstruction of the central upper lip vermillion for a relatively small defect.

Problems in breast reconstruction with deep inferior epigastric perforator (DIEP) flaps include postoperative fat induration and necrosis. A resulting clinical symptom is palpable indurated tissue, but it is difficult to measure the stiffness of transplanted fat tissues objectively at a deep site. The ability to perform shear-wave elastography (SWE) was recently added to some common ultrasonic echo devices, enabling objective three-dimensional measurements of tissue stiffness. In this study, we measured the stiffness of transplanted DIEP flaps using SWE to examine the effects of measurement sites, flap size and perforator patterns on stiffness. The subjects were 26 patients who showed induration of a transplanted flap on palpation in follow-up observation performed more than 6 months after breast reconstruction with a DIEP flap. The effects of the weight of the transplanted flap, and the diameter, number and location of the perforators on the stiffness of fat tissue were also analyzed. Within each zone, distal regions showed higher values, but in Zone II, significantly higher stiffness was also found in the proximal region. Multivariate regression analysis including all measurement sites, the weight of transplanted flap, and diameter, number and location of perforators showed that the stiffness of fat tissue was significantly higher in subjects with a larger weight flap. For safe reconstruction, it will be useful to examine the stiffness of fat tissue in individual regions of a transplanted flap retrospectively, because the examination results can be used in actual clinical practice.

PURPOSE: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Eribulin was approved for the treatment of metastatic breast cancer through the EMBRACE trial, and a subgroup analysis in this clinical trial indicated the efficacy of eribulin in patients with TNBC. However, the prognosis of patients with TNBC is still poor due to various molecular characteristics. Therefore, there is an urgent need for a more effective treatment for the management of TNBC. METHODS: We investigated the synergistic effect of a novel histone deacetylase (HDAC) inhibitor, OBP-801, and eribulin in TNBC cell lines because OBP-801 has been known to enhance the anti-tumor activities of other chemotherapeutic agents. The cell growth was analyzed, and the flow cytometry analysis was conducted to evaluate the effects on cell cycle and the induction of apoptosis. The mechanism underlying the enhancement of inhibition of TNBC cell growth was investigated through Western blot analyses. RESULTS: The combination treatment of OBP-801 with eribulin showed the synergistic inhibition of the growth in TNBC cells, involved with the enhancement of apoptosis. We, for the first time, found that eribulin upregulated survivin and also that OBP-801 could remarkably suppress the upregulation of survivin by eribulin. Moreover, this combination potently suppressed Bcl-xL and the MAPK pathway compared with either agent alone. CONCLUSION: We found that the combination of OBP-801 and eribulin synergistically inhibited the growth with apoptosis in TNBC cells, suggesting that this combination might be a promising novel strategy for treating TNBC patients.

With increasing clinical demands for MEK inhibitors in cancer treatment, overcoming the resistance to MEK inhibitors is an urgent problem to be solved. Numerous reports have shown that MEK inhibition results in the activation of PI3K-Akt signaling, which may confer apoptotic resistance to MEK inhibitors. We here demonstrate that the blockade of the mevalonate pathway using the antilipidemic drug statins represses Akt activation following MEK inhibition and induces significant apoptosis when co-treated with CH5126766 or trametinib. These events were clearly negated by the addition of mevalonate or geranylgeranyl pyrophosphate, indicating that the protein geranylgeranylation is implicated in the apoptotic resistance to MEK inhibitors. Furthermore, mechanistically, the combined treatment of CH5126766 with statins upregulated TNF-related apoptosis-inducing ligand (TRAIL), which was dependent on inhibition of the mevalonate pathway and is involved in apoptosis induction in human breast cancer MDA-MB-231 cells. The present study not only revealed that the mevalonate pathway could be targetable to enhance the efficacy of MEK inhibitors, but also proposes that combinatorial treatment of MEK inhibitors with statins may be a promising therapeutic strategy to sensitize cancer cells to apoptosis.

BACKGROUND: The C-V flap for nipple reconstruction is now one of standard surgical techniques. But decreased projection is still a problem. In recent years, it has been suggested that projection can be more easily maintained when raising of the C-flap is performed with a split thickness dermis. In this study, we examined whether decrease of projection can be prevented by raising of a C-flap with a split dermis rather than with full dermis. METHODS: A total of 49 consecutive patients who underwent reconstruction of a nipple using the C-V flap technique were enrolled. The patients included 22 who underwent surgery using a C-flap with a full thickness dermis (Group F), and 27 who underwent surgery with raising of a flap with a split thickness dermis (Group S). The size of the reconstructed nipple was measured at 2 weeks, 6 months and 1 year postoperatively for comparison between Groups F and S. RESULTS: Partial necrosis of the C-flap end occurred in 4 subjects in only Group S. The decrease in projection after 1 year postoperatively in Group S was significantly lower than that in Group F. In contrast, the teat base size in Group F tended to be greater than that in Group S, suggesting a tendency for an expanded base using a flap with a full dermis. CONCLUSIONS: Our results indicated that it is recommended to use a C-flap with a split dermis for cases with high projection of the nipple on the contralateral side.