素輪 善弘

A deep inferior epigastric artery perforator (DIEP) flap has unique variations in the anatomy of the vascular supply, and this idea has been adapted to the venous system. Venous system patterns, including connections between the superficial and deep inferior epigastric vein (SDC) or connections of the superficial inferior epigastric vein across the midline-crossing linking veins (MCLV), have gradually become recognized as a cause of fat necrosis and induration due to venous congestion. Therefore, it is important to select patients who are appropriate for transplantation by evaluating blood flow in the flap based on these patterns. The subjects were 52 consecutive patients who underwent DIEP flap breast reconstruction. Relationships of fat necrosis and induration of a transplanted flap and venous system patterns (presence of SDC on the contralateral side: cSDC or MCLV, direction and diameter of perforator vein) in the flap were investigated. Logistic regression and univariate and multivariate analyses were used to identify predictors of fat necrosis and induration of the flap. Fat necrosis and induration were detected in 17.4 and 34.8% of cases, respectively. These incidences were significantly linked to the absence of cSDC and MCLV patterns in the flap. Patients without a cSDC or MCLV pattern had harder fat tissue in Zone II, especially in the distal portion. These results suggest that the absence of a cSDC or MCLV pattern causes complications such as fat necrosis and induration in a transplanted flap. If neither pattern is detected before surgery, improvement of venous drainage is recommended.

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.

Treatment outcomes for lower extremity lymphedema (LEL) using multiple lymphaticovenular anastomoses (LVA) are still uncertain. Classification of progression of lymphedema by disease staging is a potential preoperative predictor of the efficacy of treatment, but it is difficult to judge progression of lymphedema objectively. Recent studies have indicated that lymph pump dysfunction, which reflects lymph transportation capacity, is associated with lymphedema progression. Indocyanine green (ICG) lymphography, a minimally invasive modality for pathophysiological assessment of lymphedema, can be used for rapid and objective measurement of ICG velocity (ICGv) and transit time to the knee (TTk), which are parameters of lymph transportation capacity, over a certain period. In the current study, we analyzed the relationship between these parameters and outcomes for LEL treated by multiple LVA. Thirty-four consecutive patients who underwent multiple LVA and ICG lymphography were enrolled in the study. The relationship of ICGv and TTk with the efficacy of treatment by LVA (LEL index reduction) was investigated using Pearson correlation coefficient analysis. LEL index reduction was more strongly correlated with ICGv than with TTk, whereas it was weakly correlated with both quantification methods of lymph pump function (r > 0.6). Both ICGv and TTk are objective and simple parameters that can measure lymph pump functions quickly. Lymph pump function, especially calculated with ICGv, might help predict the treatment efficacy and objective evaluation after therapeutic intervention using multiple LVA.

In reconstructions of mandibles and condyles, free fibular flaps and metallic condylar heads (CH) are often used after resection. However, in conventional reconstructions, it is difficult to fix the metallic CH on the same preoperative position because the position is determined visually. Therefore, we have made an original computer-aided design and manufacture (CAD/CAM) guide for mandibular condyle reconstruction, combining a metallic CH with a free fibular flap. A 71-year-old woman with gingival carcinoma underwent hemimandibulectomy. We reconstructed the mandible and condyle with a metallic CH and a free fibular flap. We placed a mark on the CAD/CAM guide showing the correct position for fixing the CH to the fibular blocks. We also designed a surface for attaching to the healthy edge of the mandible. The fibular blocks and metallic CH were fixed as 1 unit before separating the flap from the leg and replacing the diseased tissue. Reconstruction was completed by fixing the attachment surface to the healthy side of the mandible. The guide marks solved the difficulty of conventional reconstruction; during surgery, we fixed the metallic CH to the same position as the original bone using these marks. The postoperative deviation of the condyle from the virtual plan was 4.3 mm, whereas the reported deviation of such prostheses was 3.8 mm (range 1.3-6.7); so our guide was acceptably accurate. Furthermore, it appears that the CAD/CAM guide is more useful for reconstruction after hemimandibulectomy including the condyle than after segmental resection without including condyle.

Mandibular reconstruction using computer-aided design and computer-assisted manufacturing (CAD/CAM) techniques has received recent attention. This technique has theoretical advantages, although this approach can be commercially used in the limited area of the world.The aim is to describe our experience using in-house CAD/CAM guides and the situations in which CAD/CAM may present benefit in the region where commercial guides are unavailable.The authors developed our In-house CAD/CAM approach for mandibular reconstructions with a free fibular flap. Patients were divided into 2 group; CAD/CAM and conventional groups. In the CAD/CAM group, reconstructions were planned virtually using CAD/CAM; these CAD/CAM guides were used in the surgery. In the conventional group, free-hand cutting and fitting of the fibular segments were performed as reconstructions. Later, the bone computed tomographic image was compared with the plan. The averaged deviations and the percentages of the points within 1 mm, 2 mm, and 3 mm deviations were recorded. Total and ischemic time were also recorded.Reconstruction points within 1 mm deviation were 59% of CAD/CAM group (n = 9) and 42% of conventional group (n = 10, P = 0.04), within 2 mm 82% and 69% (P = 0.03). Total time were 1012 and 911 minutes, while flap ischemic time were 147 and 175 minutes (P = 0.03), respectively.In-house CAD/CAM mandibular reconstruction also supported accuracy and shorter flap ischemic time. For a detailed accurate reconstruction, CAD/CAM showed superiority than conventional method. Use of the In-house CAD/CAM guides might be an option where commercial guides are not available.

Chronic pain after breast surgery including breast reconstruction is a major concern for patients. However, the factors associated with chronic pain after breast surgery are uncertain in Japanese population. The aim of this study was to identify patient-specific and medical/surgical factors that predict chronic pain after breast surgery in Japanese patients. The subjects were 189 Japanese women undergoing breast surgery including tissue expander/implant (TE/implant), deep inferior epigastric perforator (DIEP) procedures and mastectomy only. Pain was assessed at one year postoperatively using a validated survey instrument: the Japanese version of the Short-Form McGill Pain Questionnaire (SF-MPQ-JV). A multiple linear regression model was used to examine the relationships of clinical factors with postoperative pain. Surveys were completed by 141 subjects. A younger age (p = .04) and bilateral procedures (p < .05) were both closely associated with the extent of increased postoperative pain at 1 year using the MPQ-Total pain rating. Compared to total mastectomy only, TE/implant procedures showed a significantly lower visual analog scale (VAS) (p = .04) and present pain index (PPI) (p = .03) scores. No factor related to chronic pain was also significantly related to the frequency of pain medication use postoperatively or the effect of social life of the patients. This study identified patients at risk for greater chronic pain after breast surgery. These findings will allow surgeons to improve patient comfort, reduce clinical morbidity and enhance patient satisfaction with their surgical outcome. Abbreviations: BMI: body mass index; CI: confidence interval; DIEP: deep inferior epigastric perforator flap; MPQ: McGill pain questionnaire; PPI: present pain index; SD: standard deviation; SF-MPQ-JV: Japanese version of the short-form McGill pain questionnaire; TE: tissue expander; VAS: visual analog scale.

: The deep inferior epigastric perforator (DIEP) flap is becoming the gold standard for breast reconstruction using autologous tissue. If there are scars in the abdomen from previous surgery, it is necessary to judge the indication for using this flap carefully. Particularly in cases with vertical midline scars, the blood flow supply to the zone II can be compromised. Even when patients have a median abdominal scar, it has been reported that the blood flow can extend beyond the scar and reach several centimeters to about half of zone II. We performed breast reconstruction using DIEP flaps for 2 patients with vertical midline scars in the lower abdomen. Indocyanine green angiography was conducted intraoperatively to confirm the vascular territory with a single pedicle before cutting off the flap. One patient showed fluorescence contrast on the contralateral side across the midline scar. However, the fluorescence contrast was absent across the midline scar in the other patient. Based on this result, we investigated the possible vascular territory of a single pedicled DIEP flap in patients with vertical midline abdominal scars. We suggest that successful blood supply to zone II of a single-pedicled DIEP flap in a patient with a vertical midline abdominal scar is related to the location of the perforator and the property of the tissue in the midline near the perforator. However, because it is difficult to predict the vascular territory of a single pedicle before surgery, intraoperative evaluation using such techniques such as indocyanine green fluorescence imaging is important.

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.