Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma.

BACKGROUND: Octamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. To date, however, the function of human OCT4 in somatic and/or tumour tissues is largely unknown. METHODS: RT-PCR was used to identify full-length splice forms of OCT4 transcripts in normal and cancer cells. A FLAG-tagged OCT4 genomic transgene was used to identify OCT4-positive cancer cells. A potential role for OCT4 in somatic cancer cells was examined by cell ablation of OCT4-positive cells using promoter-driven diphtheria toxin A. OCT4 and secreted phosphoprotein 1 (SPP1) transcripts in early-stage lung adenocarcinoma tumours were analysed and compared with pathohistological features. RESULTS: The results show that, unlike in murine cells, OCT4A and OCT4B variants are transcribed in both human cancer cells and in adult tissues such as lung, kidney, uterus, breast, and eye. We found that OCT4A and SPP1C are co-expressed in highly aggressive human breast, endometrial, and lung adenocarcinoma cell lines, but not in mesothelial tumour cell lines. Ablation of OCT4-positive cells in lung adenocarcinoma cells significantly decreased cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinoma tumours. CONCLUSIONS: Co-expression of OCT4 and SPP1 may correlate with cancer aggressiveness, and the OCT4A/SPP1C axis may help identify early-stage high-risk patients with lung adenocarcinoma. Contrary to the case in mice, our data strongly suggest a critical role for OCT4A and SPP1C in the development and progression of human epithelial cancers.

Lower-Limb Lymphatic Drainage Pathways and Lymph Nodes: A CT Lymphangiography Cadaver Study.

Background Most lymphatic imaging examinations of the lower limb require intradermal or subcutaneous injection of tracer material into the foot to demonstrate the lymphatic vessels; however, no standard protocol exists, and single or multiple injections are applied at different sites. Purpose To determine the three-dimensional relationships between each lymphatic group of the lower limb and corresponding regional lymph nodes. Materials and Methods A total of 130 lower limbs (55 from men and 75 from women) from 83 fresh human cadavers were studied. Lymphatic vessels were first visualized by using indocyanine green fluorescent lymphography with 19 injection sites in the foot, classified into four distinct lymphatic groups (anteromedial, anterolateral, posteromedial, and posterolateral); dilute oil-based contrast material was then injected. Next, specimens were scanned with CT and three-dimensional images were analyzed. Results The anteromedial and anterolateral lymphatic groups of the lower-leg lymphatic vessels were independent of each other and connected to different regional lymph nodes in the inguinal region. The posteromedial group and the anteromedial group in the lower leg drained to the same inguinal lymph nodes. Only the posterolateral group of lymphatic vessels in the lower leg drained to the popliteal lymph nodes. Leg lymphatic drainage pathways were independent of genital pathways. Conclusion Standard injection sites at the web spaces between the toes did not help visualize some lymph nodes of the lower leg. Additional injection sites in the medial, lateral, and posterior aspect of the foot would be better for evaluating the whole lymphatic pathways and regional lymph nodes and for improving understanding of leg lymphedema. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Weiss and Liddel in this issue.

Correlations between Tracer Injection Sites and Lymphatic Pathways in the Leg: A Near-Infrared Fluorescence Lymphography Study.

BACKGROUND: The primary aim of this study was to determine the detailed anatomy of the lymphatics in the lower extremity using fresh human cadavers with indocyanine green fluorescence lymphography. The secondary aim was to apply the anatomical results to establish a new protocol for lymphography based on feasible allocations for tracer injection sites. METHODS: One hundred lower extremities from 53 fresh human cadavers were used for this study. The authors injected indocyanine green solution subcutaneously at 19 points around the foot along the borderline between the dorsum and planta according to anatomical landmarks. Immediately after the indocyanine green injections, gentle hand massage was applied at each injection site to facilitate indocyanine green uptake into the lymphatic vessels. Fluorescent images of the lymphatics were obtained using a near-infrared camera system. Imaging data of the lymphatics were analyzed to find correlations between the injection sites and the identified lymphatic vessels. RESULTS: The lymphatic system in the lower extremity was divided into four distinct lymphatic groups: anteromedial, anterolateral, posterolateral, and posteromedial. The lymphatic vessels in all except the posterolateral group connected to the inguinal nodes, and those in the posterolateral group connected to the popliteal nodes. The authors successfully elucidated correlations between the injection sites in the foot and each lymphatic group. CONCLUSION: The new classification of the four lymphatic groups in the lower extremity and identification of their origins in the foot enabled the authors to propose a new protocol for lymphography that includes four injection sites in specific circumflex locations.

A Fresh Cadaver Study on Indocyanine Green Fluorescence Lymphography: A New Whole-Body Imaging Technique for Investigating the Superficial Lymphatics.

BACKGROUND: Identification of the lymphatic system in cadavers is painstaking because lymphatic vessels have very thin walls and are transparent. Selection of appropriate contrast agents is a key factor for successfully visualizing the lymphatics. In this study, the authors introduce a new imaging technique of lymphatic mapping in the whole bodies of fresh cadavers. METHODS: Ten fresh human cadavers were used for this study. The authors injected 0.1 ml of indocyanine green fluorescence solution subcutaneously at multiple spots along the watershed lines between lymphatic territories and hand and foot regions. After the body was scanned by the near-infrared camera system, fluorescent tissues were harvested and histologic examination was performed under the microscope equipped with the infrared camera system to confirm that they were the lymphatics. RESULTS: Subcutaneously injected indocyanine green was immediately transported into the lymphatic vessels after gentle massage on the injection points. Sweeping massage along the lymphatic vessels facilitated indocyanine green transport inside the lymphatic vessel to move toward the lymph nodes. The lymphatic system was visualized well in the whole body. Histologic examinations confirmed that indocyanine green was detected in the lymphatic lumens specifically, even when located far from the injected points. CONCLUSIONS: The lymphatic system could be visualized in whole-body fresh cadavers, as in living bodies, using indocyanine green fluorescence lymphography. Compatibility of indocyanine green lymphography would facilitate the use of cadaveric specimens for macroscopic and microscopic analyses.

Laser-Assisted Indocyanine Green Angiography Aids in the Reconstruction of Gustilo Grade IIIB Open Lower-Limb Fractures.

Background The treatment of trauma to the lower extremities often carries a high risk of complications. To the best of our knowledge, no study has been published regarding the treatment of open lower-limb fractures using laser-assisted indocyanine green angiography (LA-ICG). Here we retrospectively evaluated LA-ICG-based therapeutic interventions and reported the use of LA-ICG and its results in this application. Patients and Methods Between January 2011 and December 2015, a total of 23 cases with Gustilo grade IIIB open lower-limb fractures were investigated. LA-ICG was used to demonstrate the presence of necrotic tissue and determine the range of debridement. We compared 13 patients treated using LA-ICG from 2013 to 2015 with 10 patients treated without LA-ICG from 2010 to 2013. We reviewed tissue necrosis and other outcomes of these patients. Results The tissue necrosis rate in the LA-ICG-used group was significantly lower than that in the LA-ICG-free group. There were also significant differences in the average number of instances of tissue necrosis per patient, debridements, and deep-site infections. There was no flap loss. Conclusion By using LA-ICG, not only plastic surgeons but also clinicians in all associated departments including orthopedics can perform early reliable debridement and share in trauma treatment planning. We will continue to accumulate similar cases and hope to further improve LA-ICG techniques.

Non-occlusive mesenteric ischaemia of a free jejunal flap.

Free jejunal transfer using microsurgery after oesophageal or pharyngeal cancer resection is a useful operative approach. However, the disadvantage of free tissue transfer is the risk of necrosis of the transferred tissue due to impaired blood supply. In addition, jejunal flaps are more prone to blood-flow disorders such as ischaemia and congestion compared with other types of flaps. The causes of local blood supply disorders after microsurgery are divided broadly into two classes: one is thrombosis of an artery and/or vein in the anastomotic region and the other consists of local physical factors such as compressive pressure derived from haematoma formation and the effect of infection of the vascular pedicle. In this report, two rare cases of blood-flow disorder of the transferred free jejunum are described. In both cases, no signs of significant infection or occlusion of the vascular pedicles were present and late necrosis progressed gradually. The patients showed remarkable weight loss and a poor nutritional state due to inadequate preoperative nutritional intake. The necrosis was considered to be a result of non-occlusive mesenteric ischaemia of a free jejunal flap, and the factors contributing to free jejunal necrosis were reviewed.