Intranodal lymphangiography under microsurgery for refractory lymphatic ascites after pelvic lymphadenectomy.

Lymphatic ascites is a postoperative complication of lymph node dissection. Most symptomatic cases improve with conservative treatments. However, optimal management strategies for intractable lymphatic ascites remain controversial, and clinicians sometimes encounter intractable lymphatic ascites that does not respond to conservative management. We herein report a case of postoperative intractable lymphatic ascites that was successfully treated with intranodal lymphangiography (LG) from inguinal lymph nodes under microsurgery. A 56-year-old woman was diagnosed with stage II endometrial cancer and underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomies. On postoperative day (POD) 13, the patient presented with abdominal distention, and lymphatic ascites was diagnosed. Although the patient was treated with conservative management and lymphaticovenular anastomosis, her lymphatic ascites did not resolve. Finally, intranodal LG from the inguinal region was performed under microsurgery. A 2-cm incision was made on each side of the inguinal region. Once the lymph nodes were identified, a 23-gauge needle was inserted into the lymph node and lipiodol was injected. Extravasation of lipiodol into the abdomen from the left side of the lower pelvic region was confirmed. The postoperative course was uneventful. The ascites gradually decreased and disappeared within two weeks after LG.

Improving the accuracy of estimating blood calcium concentration in Holstein cows using electrocardiographic variables.

We previously reported the possibility of using the electrocardiogram variable to estimate blood calcium (Ca) concentration in dairy cows based on the strong positive correlation between the blood Ca concentration and the inverse of the corrected ST peak interval (STc-1). To improve the accuracy of the estimation of blood Ca concentration, we investigated the relationship between blood Ca concentration and STc-1 for each postpartum day and available variables other than STc-1. We measured multiple variables (milk yield, calving number, age, body temperature, etc.), including serum total Ca concentration (tCa), blood ionized Ca concentration (iCa) and STc-1 in 462 Holstein cows on days 0, 1, 2, 3, 5, and 7 postpartum. A very high correlation was observed between iCa and tCa. The association between tCa and STc-1 for each postpartum day had a high coefficient of determination of 0.61-0.79 postpartum 0-2 days but decreased after the third day. In the investigation using the data from postpartum days 0-2, STc-1, heart rate interval, calving number, and age were highly correlated with tCa. In addition, a multiple regression equation was obtained with tCa as the objective variable and STc-1 and calving number as explanatory variables. The estimation accuracy was improved as compared with the simple regression equation using only STc-1 as the explanatory variable. This multiple regression equation was used for 11 cows suspected of having hypocalcemia, and it was able to correctly detect cows requiring early treatment, except for one cow.

Fat-augmented latissimus dorsi myocutaneous flap for total breast reconstruction: A report of 54 consecutive Asian cases.

Immediate fat grafting to the latissimus dorsi myocutaneous (LD) flaps is a breakthrough that addresses the issue of insufficient volume of LD. However, the use of this procedure in Asian patients has not yet been reported. Retrospective chart reviews were conducted on 54 Japanese cases of total breast reconstruction using fat-augmented LD flaps at our hospital from September 2017 to June 2019. There were 24 immediate reconstruction cases, 18 immediate two-stage reconstruction cases, nine delayed reconstruction cases, and three delayed two-stage reconstruction cases. Median age was 46 years (range, 29-69 years), and median body mass index was 21.5 (17-33.8). Median mastectomy specimen and flap weight was 225 g (123-993) and 225 g (130-796), respectively. The median volume of fat graft was 114 ml (46-305) for the LD flap and 58 ml (15-200) for the pectoralis major muscle. Of the 53 completed reconstruction cases, 38 (71.7%) achieved sufficient volume with the initial operation and six (11.3%) required additional fat grafting. The proportion of cases in the immediate reconstruction group, which achieved sufficient volume in the initial operation was significantly higher than those of the other three reconstruction groups (p = 0.007). Total breast reconstruction with fat-augmented LD flaps is a viable procedure for thin patients who have insufficient abdominal tissue, for those who wish to avoid abdominal scars, and for those in whom abdominal flaps have already been used. The procedure allows for large volume transplantation even with small skin paddles, which allows for smaller skin paddles to be designed without the need for extensive subcutaneous dissection.

A Simple and Scarless Method for Inframammary Fold Correction Using a Barbed Suture.

BACKGROUND: In the typical procedure for secondary correction of the inframammary fold (IMF) following breast reconstruction, a large incision is often required, and this increases surgical invasiveness. The "drawstring method" is a simple procedure for recreating a smooth IMF. We modified the drawstring method and developed an essentially scarless method for IMF correction from small stab incisions. METHODS: Patients at our hospital who presented with IMF ptosis or loss of definition after breast reconstruction and required IMF correction, as well as those who requested IMF recreation for the contralateral breast, during the period spanning May 2016 to June 2019 were considered for this study. We collected and analyzed demographic data, as well as complications and postoperative outcomes. RESULTS: The new method was performed on 20 patients, with the following breakdown: IMF recreation after breast reconstruction with a deep inferior epigastric artery perforator flap (11 patients), IMF recreation after breast reconstruction with a breast implant (2 patients), IMF recreation after breast reconstruction with fat graft (5 patients), and IMF recreation for the contralateral breast (2 patients). Overcorrection of the IMF stabilized by 2-3 months postoperatively, resulting in a smooth and well-defined IMF. For non-breast implant cases, the implant volume increased at the lower pole. Slack in the suture was observed in only 2 patients of the deep inferior epigastric artery perforator group and in 1 patient of the breast implant group after 6 months postoperatively. CONCLUSIONS: Our new method allows for the recreation of an essentially scarless, smooth, and well-defined IMF. IMF definition can be adjusted by altering the depth of the barbed suture. Since this method can be performed under local anesthesia, it offers the benefits of reducing medical costs and physical burden on patients.

Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-ß1 secretion in abnormal scar formation.

Excess scar formation can occur after skin injurふy and lead to abnormal scar formation, such as keloids and hypertrophic scars, which are characterised by substantial deposition of extracellular matrix in the dermis. Periostin, an extracellular matrix protein that plays a crucial role in skin development and maintaining homeostasis, is also involved in skin disorders such as systemic/limited scleroderma, wound closure, and abnormal scar formation. However, the mechanism of periostin involvement in abnormal scar formation is not yet fully understood. In this study, we investigated the mechanism by which periostin is involved in abnormal scar formation. Treatment of human dermal fibroblasts (HDFs) with IL-4 and IL-13, which are cytokines of Th2 type immune responses that are up-regulated in abnormal scars, dramatically elevated the levels of periostin mRNA and protein, and also promoted the secretion of periostin by HDFs. Transforming growth factor-ß1 (TGF-ß1) had the same effect on HDFs as IL-4 and IL-13. Stimulation of HDFs with periostin promoted RhoA/ROCK pathway-mediated TGF-ß1 secretion from HDFs. Our results suggest that IL-4 and IL-13 induce periostin expression and secretion, and in turn, secreted periostin induces RhoA/ROCK pathway-mediated TGF-ß1 secretion. Secreted TGF-ß1 then induces further periostin production and secretion, thereby promoting abnormal scar formation.

Endothelial cell-derived endothelin-1 is involved in abnormal scar formation by dermal fibroblasts through RhoA/Rho-kinase pathway.

Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars. We also confirmed that ET-1 induced myofibroblast differentiation and collagen synthesis in cultured human dermal fibroblasts through the RhoA/Rho-kinase pathway. Finally, since hypertrophic scar/keloid formation was most prominent in areas exposed to mechanical stretch, we examined how mechanical stretch affected ET-1 secretion in human dermal microvascular ECs, and found that mechanical stretch increased ET-1 gene expression and secretion from ECs. Taken together, these results suggest that dermal microvascular ECs release ET-1 in response to mechanical stretch, and thereby contribute to the formation of hypertrophic scars and keloids through the RhoA/Rho-kinase pathway.

Effects of Breast Shielding during Heart Imaging on DNA Double-Strand-Break Levels: A Prospective Randomized Controlled Trial.

Purpose To examine the effect of breast shielding on blood lymphocyte deoxyribonucleic acid (DNA) double-strand-break levels resulting from in vivo radiation and ex vivo radiation at breast-tissue level, and the effect of breast shielding on image quality. Materials and Methods The study was approved by institutional review and commpliant with HIPAA guidelines. Adult women who underwent 64-section coronary computed tomographic (CT) angiography and who provided informed consent were prospectively randomized to the use (n = 50) or absence (n = 51) of bismuth breast shields. Peripheral blood samples were obtained before and 30 minutes after in vivo radiation during CT angiography to compare DNA double-strand-break levels by γ-H2AX immunofluorescence in blood lymphocytes. To estimate DNA double-strand-break induction at breast-tissue level, a blood sample was taped to the sternum for ex vivo radiation with or without shielding. Data were analyzed by linear regression and independent sample t tests. Results Breast shielding had no effect on DNA double-strand-break levels from ex vivo radiation of blood samples under shields at breast-tissue level (unadjusted regression: ß = .08; P = .43 versus no shielding), or in vivo radiation of circulating lymphocytes (ß = -.07; P = .50). Predictors of increased DNA double-strand-break levels included total radiation dose, increasing tube potential, and tube current (P < .05). With current radiation exposures (median, 3.4 mSv), breast shielding yielded a 33% increase in image noise and 19% decrease in the rate of excellent quality ratings. Conclusion Among women who underwent coronary CT angiography, breast shielding had no effect on DNA double-strand-break levels in blood lymphocytes exposed to in vivo radiation, or ex vivo radiation at breast-tissue level. At present relatively low radiation exposures, breast shielding contributed to an increase in image noise and a decline in image quality. The findings support efforts to minimize radiation by primarily optimizing CT settings. (©) RSNA, 2016 Clinical trial registration no. NCT02617888 Online supplemental material is available for this article.

The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induces mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reverses these changes, as does silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibit a similar metastatic behaviour, but the cells with re-expressed H2A.X are substantially more metastatic. We surmise that H2A.X re-expression leads to partial EMT reversal and increases robustness in the HCT116 cells, permitting them to both form tumours and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlate inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a regulator of EMT.

Regulatory Frameworks for Gene and Cell Therapies in Japan.

The regulations for the human use of advanced therapy medical products such as gene and cell therapy products have evolved in accordance with advance of clinical experience, scientific knowledge, and social acceptance to these technologies. In Japan, two laws, the Pharmaceuticals and Medical Devices (PMD) Act and the Act on the Safety of Regenerative Medicine (ASRM), were enacted in November 2014. The PMD Act defines regenerative medical products for the first time and introduces a system for the conditional and time-limited marketing authorization of regenerative medical products. Under ASRM, the responsibilities of medical institutions to ensure the safety and provide transparency of such medical technologies are described. Amendments to accompanying guidelines for these two Acts are currently in preparation. It is expected that the new legislative frameworks will promote the timely development of new products and technologies, to bring safe and effective regenerative medicines to Japanese patients.

Report of the international conference on regulatory endeavors towards the sound development of human cell therapy products.

The regulation of human cell therapy products is a key factor in their development and use to treat human diseases. In that regard, there is a recognized need for a global effort to develop a set of common principles that may serve to facilitate a convergence of regulatory approaches to ensure the smooth and efficient evaluation of products. This conference, with experts from regulatory agencies, industry, and academia, contributed to the process of developing such a document. Elements that could form a minimum consensus package of requirements for evaluating human cell therapy products were the overall focus of the conference. The important regulatory considerations that are unique to human cell therapy products were highlighted. Sessions addressed specific points that are different from those of traditional biological/biotechnological protein products. Panel discussions complemented the presentations. The conference concluded that most of the current regulatory framework is appropriate for cell therapy, but there are some areas where the application of the requirements for traditional biologicals is inappropriate. In addition, it was agreed that there is a need for international consensus on core regulatory elements, and that one of the major international organizations should take the lead in formulating such a consensus document.

Usefulness of interventional embolization of the middle meningeal artery for recurrent chronic subdural hematoma: Five cases and a review of the literature.

PURPOSE: Although several strategies against recurrent chronic subdural hematoma (CSDH) have been proposed, no consensus has been established. Recently, middle meningeal artery (MMA) embolization has been proposed as radical treatment for recurrent CSDH. We wanted to estimate the usefulness of MMA embolization for recurrent CSDH. METHODS: From February 2012 to June 2013, 110 patients with CSDH underwent single burr-hole surgery with irrigation and drainage. Among these patients, 13 showed recurrent hematoma formation and were retreated surgically. Furthermore, repeated recurrence of CSDH was observed in six patients. Five of these six patients underwent middle meningeal artery (MMA) embolization with polyvinyl alcohol particles. All five patients with interventional treatment were observed for four to 60 weeks. RESULTS: No more recurrence of CSDH was observed in any of the patients. During the follow-up period, no patients suffered from any side effects or complications from the interventional treatment. CONCLUSION: MMA embolization with careful attention paid to the procedure might be a treatment of choice for recurrent CSDH.

NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease.

Ataxia telangiectasia (A-T), a rare autosomal recessive disorder characterized by progressive cerebellar degeneration and a greatly increased incidence of cancer among other symptoms, is caused by a defective or missing ataxia telangiectasia mutated (ATM) gene. The ATM protein has roles in DNA repair and in the regulation of reactive oxygen species (ROS). Here, we provide, to our knowledge, the first evidence that NADPH oxidase 4 (NOX4) is involved in manifesting A-T disease. We showed that NOX4 expression levels are higher in A-T cells, and that ATM inhibition leads to increased NOX4 expression in normal cells. A-T cells exhibit elevated levels of oxidative DNA damage, DNA double-strand breaks and replicative senescence, all of which are partially abrogated by down-regulation of NOX4 with siRNA. Sections of degenerating cerebelli from A-T patients revealed elevated NOX4 levels. ATM-null mice exhibit A-T disease but they die from cancer before the neurological symptoms are manifested. Injecting Atm-null mice with fulvene-5, a specific inhibitor of NOX4 and NADPH oxidase 2 (NOX2), decreased their elevated cancer incidence to that of the controls. We conclude that, in A-T disease in humans and mice, NOX4 may be critical mediator and targeting it will open up new avenues for therapeutic intervention in neurodegeneration.

Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage.

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year.

A hybrid electro-optic polymer and TiO2 double-slot waveguide modulator.

An electro-optic (EO) modulator using a TiO2 slot hybrid waveguide has been designed and fabricated. Optical mode calculations revealed that the mode was primarily confined within the slots when using a double-slot configuration, thus achieving a high EO activity experimentally. The TiO2 slots also acted as an important barrier to induce an enhanced DC field during the poling of the EO polymer and the driving of the EO modulator. The hybrid phase modulator exhibited a driving voltage (Vπ) of 1.6 V at 1550 nm, which can be further reduced to 0.8 V in a 1 cm-long push-pull Mach-Zehnder interferometer (MZI) structure. The modulator demonstrated a low propagation loss of 5 dB/cm and a relatively high end-fire coupling efficiency.

TiO2 ring-resonator-based EO polymer modulator.

In this work, an electro-optic (EO) ring resonator modulator was designed and fabricated in a waveguide consisting of a titanium dioxide (TiO)2 core, silicon dioxide (SiO2) buffer layer, EO polymer claddings, and electrodes. By optimizing the thickness of the TiO2 and SiO2layers, the modulator could satisfy the single-mode requirement; furthermore 52.5% TM mode was confined in the active EO polymer layers. The designed modulator could also pole the EO polymer effectively regardless of its resistivity. Therefore, the EO modulator was observed to show a high resonance wavelength shift of 2.25 × 10(-2) nm/V. The intensity modulation at 1550 nm showed a Vp-p = 1.9 V for a 3dB distinction ratio.

Exposure of a microvascular anastomotic coupler in head and neck reconstruction: a case report.

OBJECTIVE: We present a case of exposure of a microvascular anastomotic coupler. METHODS: We performed venous anastomoses using microvascular anastomotic couplers in head and neck reconstruction. RESULTS: A microvascular anastomotic coupler was exposed in the seventh month postoperation, and an anastomosed vein was disrupted. CONCLUSIONS: Although the usefulness of the microvascular anastomotic coupler in microsurgical flap reconstruction is not in doubt, as described previously, we believe that it is necessary to remember that use of a microvascular anastomotic coupler involves potential risks of exposure and anastomosed vessel disruption.

Trigeminal trophic syndrome: report of 2 cases.

OBJECTIVE: We present 2 cases of trigeminal trophic syndrome treated by surgery. METHODS: We performed reconstruction of the ala nasi using a nasolabial flap or paramedian forehead flap in combination with an auricular chondrocutaneous composite graft. RESULTS: One case was successfully treated. However, ulceration recurred intermittently in the other case. CONCLUSIONS: Although trigeminal trophic syndrome is rare, we believe that plastic surgeons should have a raised awareness of this entity and familiarity with the treatment options.

Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.

There is a paucity of large animal models to study both the extent and the health risk of ionizing radiation exposure in humans. One promising candidate for such a model is the minipig. Here, we evaluate the minipig for its potential in γ-H2AX-based biodosimetry after exposure to ionizing radiation using both Cs137 and Co60 sources. γ-H2AX foci were enumerated in blood lymphocytes and normal fibroblasts of human and porcine origin after ex vivo γ-ray irradiation. DNA double-strand break repair kinetics in minipig blood lymphocytes and fibroblasts, based on the γ-H2AX assay, were similar to those observed in their human counterparts. To substantiate the similarity observed between the human and minipig we show that minipig fibroblast radiosensitivity was similar to that observed with human fibroblasts. Finally, a strong γ-H2AX induction was observed in blood lymphocytes following minipig total body irradiation. Significant responses were detected 3 days after 1.8 Gy and 1 week after 3.8 and 5 Gy with residual γ-H2AX foci proportional to the initial radiation doses. These findings show that the Gottingen minipig provides a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans.