Novel locally nebulized indocyanine green for simultaneous identification of tumor margin and intersegmental plane.

BACKGROUND: Segmentectomy, recommended for early-stage lung cancer or compromised lung function, demands precise tumor detection and intersegmental plane identification. While Indocyanine green (ICG) commonly aids in these aspects using near-infrared (NIR) imaging, its separate administrations through different routes and times can lead to complications and patient anxiety. This study aims to develop a lung-specific delivery method by nebulizing low-dose ICG to targeted lung segments, allowing simultaneous detection of lung tumors and intersegmental planes across diverse animal models. METHODS: To optimizing the dose of ICG for lung tumor and interlobar fissure detection, different doses of ICG (0.25, 0.1 and 0.05 mg/kg) were nebulized to rabbit lung tumor models. The distribution of locally nebulized ICG in targeted segments was studied to evaluate the feasibility of detecting lung tumor and intersegmental planes in canine lung pseudotumor models. RESULTS: NIR fluorescence imaging demonstrated clear visualization of lung tumor margin and interlobar fissure using local nebulization of 0.1 mg/kg ICG for only 4 min during surgery in the rabbit models. In the canine model, the local nebulization of 0.05 mg/kg of ICG into the target segment enabled clear visualization of pseudotumor and intersegmental planes for 30 min. CONCLUSIONS: This innovative approach achieves a reduction in ICG dose and prolonged the visualization time of the intersegmental plane and effectively eliminates the need for the hurried marking of tumors and intersegmental planes. We anticipate that lung specific delivery of ICG will prove valuable for image-guided limited resection of lung tumors in clinical practice.

Evaluation of Human Platelet Lysate as an Alternative to Fetal Bovine Serum for Potential Clinical Applications of Stem Cells from Human Exfoliated Deciduous Teeth.

In recent years, there has been a surge in demand for and research focus on cell therapy, driven by the tissue-regenerative and disease-treating potentials of stem cells. Among the candidates, dental pulp stem cells (DPSCs) or human exfoliated deciduous teeth (SHED) have garnered significant attention due to their easy accessibility (non-invasive), multi-lineage differentiation capability (especially neurogenesis), and low immunogenicity. Utilizing these stem cells for clinical purposes requires careful culture techniques such as excluding animal-derived supplements. Human platelet lysate (hPL) has emerged as a safer alternative to fetal bovine serum (FBS) for cell culture. In our study, we assessed the impact of hPL as a growth factor supplement for culture medium, also conducting a characterization of SHED cultured in hPL-supplemented medium (hPL-SHED). The results showed that hPL has effects in enhancing cell proliferation and migration and increasing cell survivability in oxidative stress conditions induced by H2O2. The morphology of hPL-SHED exhibited reduced size and elongation, with a differentiation capacity comparable to or even exceeding that of SHED cultured in a medium supplemented with fetal bovine serum (FBS-SHED). Moreover, no evidence of chromosome abnormalities or tumor formation was detected. In conclusion, hPL-SHED emerges as a promising candidate for cell therapy, exhibiting considerable potential for clinical investigation.

Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism.

Oral cancer stands as a prevalent maligancy worldwide; however, its therapeutic potential is limited by undesired effects and complications. As a medicinal edible fungus, Chaga mushroom (Inonotus obliquus) exhibits anticancer effects across diverse cancers. Yet, the precise mechanisms underlying its efficacy remain unclear. We explored the detailed mechanisms underlying the anticancer action of Chaga mushroom extract in oral cancer cells (HSC-4). Following treatment with Chaga mushroom extracts, we analyzed cell viability, proliferation capacity, glycolysis, mitochondrial respiration, and apoptosis. Our findings revealed that the extract reduced cell viability and proliferation of HSC-4 cells while arresting their cell cycle via suppression of STAT3 activity. Regarding energy metabolism, Chaga mushroom extract inhibited glycolysis and mitochondrial membrane potential in HSC-4 cells, thereby triggering autophagy-mediated apoptotic cell death through activation of the p38 MAPK and NF-κB signaling pathways. Our results indicate that Chaga mushroom extract impedes oral cancer cell progression, by inhibiting cell cycle and proliferation, suppressing cancer cell energy metabolism, and promoting autophagy-mediated apoptotic cell death. These findings suggest that this extract is a promising supplementary medicine for the treatment of patients with oral cancer.

Robotic thoracic surgery using the single-port robotic system: Initial experience with more than 100 cases.

OBJECTIVE: This study aimed to report the initial experiences of 115 patients who underwent robotic thoracic surgery using the da Vinci single-port robotic surgical system (Intuitive Surgical). METHODS: Robotic thoracic surgery using the da Vinci single-port robotic surgical system was performed on 115 patients between November 2020 and June 2023. Patient characteristics, intraoperative outcomes, and postoperative outcomes were analyzed retrospectively. RESULTS: The type of surgeries included thymectomy, mediastinal mass excision, anatomical pulmonary resection (including lobectomy and segmentectomy), esophagectomy, and enucleation of esophageal submucosal tumors in 41, 13, 54, 5, and 2 patients, respectively. The mean total operative time and chest tube duration for different procedures were as follows: thymectomy, 152.9. ± 6.7 minutes and 1.2 ± 0.5 days; mediastinal mass excision, 93.3 ± 26.5 minutes and 1.0 ± 0 days; anatomical pulmonary resection, 187.2 ± 55.8 minutes and 2.5 ± 1.5 days; esophagectomy, 485 ± 111.9 minutes and 12 ± 4.6 days; and enucleation of esophageal submucosal tumors, 170 ± 30 minutes and 5.5 ± 0.5 days, respectively. Conversion to a thoracotomy or sternotomy was not required. Conversion to video-assisted thoracic surgery occurred in 1 patient, and an additional port was applied in 2 patients. Two patients experienced postoperative complications greater than grade IIIa. CONCLUSIONS: Robotic thoracic surgery using the da Vinci single-port robotic surgical system is feasible and safe in various fields of thoracic surgery, including complex procedures such as anatomical pulmonary resection and esophagectomy. More complex thoracic surgeries can be performed with the continuous advancement and innovation of instruments in robotic systems.

Simultaneous Visualization of Lung Tumor and Intersegmental Plane during Pulmonary Segmentectomy by Intravenous Injection of Indocyanine Green.

Segmentectomy is a targeted surgical approach tailored for patients with compromised health and early-stage lung cancer. The key to successful segmentectomy lies in precisely identifying the tumor and intersegmental planes to ensure adequate resection margins. In this study, we aimed to enhance this process by simultaneously visualizing the tumor and intersegmental planes through the intravenous injection of indocyanine green (ICG) at different time points and doses. Lung tumors were detected by intravenous injection of ICG at a dose of 2 mg/kg 12 h before surgery in a rabbit model. Following the dissection of the pulmonary artery, vein, and bronchi of the target segment, 0.6 mg/kg of ICG was injected intravenously to detect the intersegmental plan. Fluorescent images of the lung tumors and segments were acquired, and the fluorescent signal was quantified using the signal-to-background ratio (SBR). Finally, a pilot study of this method was conducted in three patients with lung cancer. In a preclinical study, the SBR of the tumor (4.4 ± 0.1) and nontargeted segments (10.5 ± 0.8) were significantly higher than that of the targeted segment (1.6 ± 0.2) (targeted segment vs. nontarget segment, p < 0.0001; target segment vs. tumor, p < 0.01). Consistent with preclinical results, lung tumors and the intersegmental plane were successfully detected in patients with lung cancer. Consequently, adequate resection margins were identified during the surgery, and segmentectomy was successfully performed in patients with lung cancer. This study is the first to use intravenous ICG injections at different time points and doses to simultaneously detect lung cancer and intersegmental planes, thereby achieving segmentectomy for lung cancer.

Long-term Outcomes of Patients With Early Gastric Cancer Who Had Lateral Resection Margin-Positive Tumors Based on Pathology Following Endoscopic Submucosal Dissection.

PURPOSE: Long-term outcomes of patients with positive lateral margins (pLMs) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study aimed to evaluate the remnant cancer and survival rates of patients with pLMs compared with those who underwent curative resection. MATERIALS AND METHODS: A retrospective analysis was performed on consecutive patients with pLMs as the only non-curative factor of expanded indication who underwent ESD for EGC with a follow-up duration of 5 years or more. The rates of remnant cancer, recurrence, and survival were analyzed and compared to those of control patients who underwent curative resection by propensity score matching. RESULTS: Among 3,515 patients treated with ESD between 2005 and 2018, 123 non-curative EGCs were retrospectively analyzed. A total of 108 patients were followed up without endoscopic or surgical resection for 8.2 years. The control group was matched in a 1:1 ratio with patients with EGC who underwent curative resection after ESD. The observation group with pLMs had a higher incidence of remnant cancer (25.9%; 28/108) compared to that in the curative resection group (0/108; P=0.000). The remaining tumors were treated with surgical or endoscopic resection, and no additional recurrences were observed. The overall survival analysis demonstrated no significant difference between the observation and curative resection groups (P=0.577). CONCLUSIONS: No difference was observed in the overall survival rate between observation and curative resection groups. Therefore, observation may be a possible option for incomplete ESD with pLMs if continuous follow-up is performed.

Risk Assessment of Metachronous Gastric Neoplasm after Endoscopic Resection for Early Gastric Cancer According to Age at Helicobacter pylori Eradication.

Background/Aims: Helicobacter pylori eradication can reduce the incidence of metachronous gastric neoplasm (MGN) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study evaluated the risk of developing MGN after ESD for EGC based on age at H. pylori eradication. Methods: Data of patients who underwent curative ESD for EGC with H. pylori infection between 2005 and 2018 were retrospectively analyzed. The patients were allocated to four groups according to age at H. pylori eradication: group 1 (<50 years), group 2 (50-59 years), group 3 (60-69 years), and group 4 (≥70 years). Results: All patients were followed up for at least 5 years after ESD. The 5-year cumulative incidence of MGN was 2.1%, 7.0%, 8.7%, and 16.7% in groups 1, 2, 3, and 4, respectively (p<0.001), and groups 3 and 4 showed a significant increase in the risk of MGN (hazard ratio [HR], 4.66; 95% confidence interval [CI], 1.09 to 19.92 and HR, 10.75; 95% CI, 2.45 to 47.12). After adjustments for moderate to severe intestinal metaplasia based on the updated Sydney system, groups 3 and 4 remained significantly associated with MGN (HR, 4.40; 95% CI, 1.03 to 18.84 and HR, 10.14; 95% CI, 2.31 to 44.57). Conclusions: The incidence of MGN after ESD for EGC increased with age at H. pylori eradication. Age at H. pylori eradication ≥60 years was an independent risk factor for MGN, even after adjusting for the presence of advanced intestinal metaplasia.

Poly(ADP-ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation.

PARP-1 over-activation results in cell death via excessive PAR generation in different cell types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered in brain ischemia. Studies show that PAR generated after PARP-1 over-activation can bind hexokinase-1 (HK-1) and result in glycolytic defects and subsequent mitochondrial dysfunction. HK-1 is the neuronal hexokinase and catalyzes the first reaction of glycolysis, converting glucose to glucose-6-phosphate (G6P), a common substrate for glycolysis, and the pentose phosphate pathway (PPP). PPP is critical in maintaining NADPH and GSH levels via G6P dehydrogenase activity. Therefore, defects in HK-1 will not only decrease cellular bioenergetics but will also cause redox imbalance due to the depletion of GSH. In brain ischemia, whether PAR-mediated inhibition of HK-1 results in bioenergetics defects and redox imbalance is not known. We used oxygen-glucose deprivation (OGD) in mouse cortical neurons to mimic brain ischemia in neuronal cultures and observed that PARP-1 activation via PAR formation alters glycolysis, mitochondrial function, and redox homeostasis in neurons. We used pharmacological inhibition of PARP-1 and adenoviral-mediated overexpression of wild-type HK-1 (wtHK-1) and PAR-binding mutant HK-1 (pbmHK-1). Our data show that PAR inhibition or overexpression of HK-1 significantly improves glycolysis, mitochondrial function, redox homeostasis, and cell survival in mouse cortical neurons exposed to OGD. These results suggest that PAR binding and inhibition of HK-1 during OGD drive bioenergetic defects in neurons due to inhibition of glycolysis and impairment of mitochondrial function.

Single-port robotic subcostal major pulmonary resection using the single-port robotic system.

BACKGROUND: The da Vinci single-port system (SPS) (Intuitive Surgical, Sunnyvale, CA, USA) was designed for single-port (SP) surgery. Although we have reported our clinical outcomes using the SPS for a simple procedure in general thoracic surgery, major pulmonary resection had been performed only in cadaveric experiments to date. This study evaluated the feasibility of SP subcostal robotic major pulmonary resection using the SPS. Here, we present our initial clinical experience of SP subcostal robotic major pulmonary resection at our institution. METHODS: Twenty-five patients with lung cancer underwent SP major subcostal pulmonary resection using the SPS between March and November 2022. Patient characteristics, intraoperative and perioperative outcomes were assessed. Questionnaires were used to evaluate patient satisfaction with the cosmetic results and quality of life through face-to-face or telephone interviews on postoperative day 30. RESULTS: All patients underwent major pulmonary resection with complete radical resection (R0). Nineteen patients underwent lobectomy, whereas six patients underwent segmentectomy. The mean docking time and total operative time were 4.16 ± 1.19 min (range, 2.3-7.8 min) and 197.6 ± 55.33 min (range, 130-313 min), respectively. No patients underwent conversion to open thoracotomy. One patient required an additional assistant port due to severe pleural adhesions. CONCLUSIONS: SP subcostal robotic major pulmonary resection using the SPS is feasible and safe. With the continuous development of robotic technology and surgical techniques, we believe that more complex general thoracic surgeries will be performed in the future using SPS.

Development and External Validation of 18F-FDG PET-Based Radiomic Model for Predicting Pathologic Complete Response after Neoadjuvant Chemotherapy in Breast Cancer.

The aim of our retrospective study is to develop and externally validate an 18F-FDG PET-derived radiomics model for predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 87 breast cancer patients underwent curative surgery after NAC at Soonchunhyang University Seoul Hospital and were randomly assigned to a training cohort and an internal validation cohort. Radiomic features were extracted from pretreatment PET images. A radiomic-score model was generated using the LASSO method. A combination model incorporating significant clinical variables was constructed. These models were externally validated in a separate cohort of 28 patients from Soonchunhyang University Buscheon Hospital. The model performances were assessed using area under the receiver operating characteristic (AUC). Seven radiomic features were selected to calculate the radiomic-score. Among clinical variables, human epidermal growth factor receptor 2 status was an independent predictor of pCR. The radiomic-score model achieved good discriminability, with AUCs of 0.963, 0.731, and 0.729 for the training, internal validation, and external validation cohorts, respectively. The combination model showed improved predictive performance compared to the radiomic-score model alone, with AUCs of 0.993, 0.772, and 0.906 in three cohorts, respectively. The 18F-FDG PET-derived radiomic-based model is useful for predicting pCR after NAC in breast cancer.

Optimization of Indocyanine Green for Intraoperative Fluorescent Image-Guided Localization of Lung Cancer; Analysis Based on Solid Component of Lung Nodule.

ICG fluorescence imaging has been used to detect lung cancer; however, there is no consensus regarding the optimization of the indocyanine green (ICG) injection method. The aim of this study was to determine the optimal dose and timing of ICG for lung cancer detection using animal models and to evaluate the feasibility of ICG fluorescence in lung cancer patients. In a preclinical study, twenty C57BL/6 mice with footpad cancer and thirty-three rabbits with VX2 lung cancer were used. These animals received an intravenous injection of ICG at 0.5, 1, 2, or 5 mg/kg, and the cancers were detected using a fluorescent imaging system after 3, 6, 12, and 24 h. In a clinical study, fifty-one patients diagnosed with lung cancer and scheduled to undergo surgery were included. Fluorescent images of lung cancer were obtained, and the fluorescent signal was quantified. Based on a preclinical study, the optimal injection method for lung cancer detection was 2 mg/kg ICG 12 h before surgery. Among the 51 patients, ICG successfully detected 37 of 39 cases with a consolidation-to-tumor (C/T) ratio of >50% (TNR: 3.3 ± 1.2), while it failed in 12 cases with a C/T ratio ≤ 50% and 2 cases with anthracosis. ICG injection at 2 mg/kg, 12 h before surgery was optimal for lung cancer detection. Lung cancers with the C/T ratio > 50% were successfully detected using ICG with a detection rate of 95%, but not with the C/T ratio ≤ 50%. Therefore, further research is needed to develop fluorescent agents targeting lung cancer.

NK cells encapsulated in micro/macropore-forming hydrogels via 3D bioprinting for tumor immunotherapy.

BACKGROUND: Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results. METHOD: To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels. RESULTS: It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model. CONCLUSION: We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.

Human Fibroblast Growth Factor-Treated Adipose-Derived Stem Cells Facilitate Wound Healing and Revascularization in Rats with Streptozotocin-Induced Diabetes Mellitus.

Diabetes mellitus contributes to 15-25% of all chronic foot ulcers. Peripheral vascular disease is a cause of ischemic ulcers and exacerbates diabetic foot disease. Cell-based therapies are viable options to restore damaged vessels and induce the formation of new vessels. Adipose-derived stem cells (ADSCs) have the potential for angiogenesis and regeneration because of their greater paracrine effect. Preclinical studies are currently using other forced enhancement techniques (e.g., genetic modification or biomaterials) to increase the efficacy of human ADSC (hADSC) autotransplantation. Unlike genetic modifications and biomaterials, many growth factors have been approved by the equivalent regulatory authorities. This study confirmed the effect of enhanced human ADSC (ehADSC)s with a cocktail of FGF and other pharmacological agents to promote wound healing in diabetic foot disease. In vitro, ehADSCs exhibited a long and slender spindle-shaped morphology and showed significantly increased proliferation. In addition, it was shown that ehADSCs have more functionalities in oxidative stress toleration, stem cell stemness, and mobility. In vivo, the local transplantation of 1.2 × 106 hADSCs or ehADSCs was performed in animals with diabetes induced by STZ. The ehADSC group showed a statistically decreased wound size and increased blood flow compared with the hADSC group and the sham group. Human Nucleus Antigen (HNA) positive cells were observed in some ADSC-transplanted animals. The ehADSC group showed a relatively higher portion of HNA-positive animals than the hADSC group. The blood glucose levels showed no significant difference among the groups. In conclusion, the ehADSCs showed a better performance in vitro, compared with conventional hADSCs. Additionally, a topical injection of ehADSCs into diabetic wounds enhanced wound healing and blood flow, while improving histological markers suggesting revascularization.

Casein Kinase 2α Augments Oxaliplatin Resistance in Colorectal Cancer Cells by Increasing ABCE1 Expression.

BACKGROUND/AIM: Antitumor drug resistance is a major hurdle in treating patients with malignant tumors. Casein kinase 2α (CK2α) expression is highly enhanced in oxaliplatin-resistant CRC cells. We investigated whether CK2α expression is associated with oxaliplatin resistance in CRC cells. MATERIALS AND METHODS: To determine the effect of CK2α on drug resistance in CRC, we assessed the cell viability, adenosine triphosphate-binding cassette (ABC) transporter expression, apoptosis, and sphere formation according to CK2α expression in oxaliplatin-resistant CRC cells. RESULTS: CK2α expression was significantly increased in oxaliplatin-resistant CRC cells compared with that in wild-type CRC cells. In addition, the mRNA expression of ABC transporters, including ABCA12, ABCC2, and ABCE1, was significantly enhanced in oxaliplatin-resistant CRC cells, whereas this effect was blocked by the knockdown of CK2α. Furthermore, a cell viability test showed that oxaliplatin resistance was inhibited by decreasing CK2α expression, resulting in the induction of apoptosis and suppression of sphere formation. CONCLUSION: CK2α regulates cell survival, apoptosis, sphere formation, and drug resistance in oxaliplatin-resistant CRC cells by regulating ABC transporters. Therefore, targeting CK2α in drug-resistant CRC cells may be a novel strategy for treating patients with CRC.

Biportal robotic surgery for anterior mediastinal mass.

Background: Robotic-assisted surgery for mediastinal disease has been shown to be beneficial in facilitating easier mediastinal dissection with its three-dimensional views and multi-articulated moving instruments. Herein, we report our experience with the biportal approach of robot-assisted anterior mediastinal mass surgery, including both lateral transthoracic and subxiphoid approaches. Methods: We retrospectively analyzed 21 patients who underwent biportal robotic-assisted anterior mediastinal mass resection, without considering the tumor size between May 2018 and September 2022. We reviewed the technical advantages and limitations of the biportal approach and the perioperative outcomes, including operative time, conversion to multiport or open surgery, duration of chest drainage, and postoperative complications, to define the role of robot-assisted surgery using the biportal approach. Results: We approached the thoracic cavity from the right side in five patients, from the left side in three patients, and from the subxiphoid in 13 patients. Thymomas (n=13) and thymic cysts (n=3) were the most common diagnoses. The median operative time was 165 min [interquartile range (IQR), 140-196 min]. There were no conversions to multiport or open surgery. The chest drain was removed at a median of two days (IQR, 1-3 days), and the patients were discharged at a median of four days (IQR, 3-5 days). Perioperative complications were reported in two patients (one with prolonged air leak and one with vocal cord palsy). There were no cases of readmission or delayed complication. Conclusions: The biportal approach for robot-assisted surgery in anterior mediastinal masses is a feasible and safe alternative for treating associated pathologies. The subxiphoid approach for mediastinal surgery provides a better surgical view than the transthoracic approach. The biportal approach also enables the use of robotic staplers and energy devices and minimizes instrumental interference compared to that in the single-port approach.

Identification of Metastatic Lymph Nodes Using Indocyanine Green Fluorescence Imaging.

Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated the potential of ICG. The feasibility of detecting metastatic LNs was also evaluated in patients with lung or esophageal cancer, detected with computed tomography (CT) or positron-emission tomography (PET)/CT, and scheduled to undergo surgical resection. Tumors and metastatic LNs were successfully detected in the mice. In the clinical study, the efficacy of ICG was evaluated in 15 tumors and fifty-four LNs with suspected metastasis or anatomically key regional LNs. All 15 tumors were successfully detected. Among the fifty-four LNs, eleven were pathologically confirmed to have metastasis; all eleven were detected in ICG fluorescence imaging, with five in CT and seven in PET/CT. Furthermore, thirty-four LNs with no signals were pathologically confirmed as nonmetastatic. Intravenous injection of ICG may be a useful tool to detect metastatic LNs and tumors. However, ICG is not a targeting agent, and its relatively low fluorescence makes it difficult to use to detect tumors in vivo. Therefore, further studies are needed to develop contrast agents and devices that produce increased fluorescence signals.

Fructose-1,6-bisphosphatase is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness.

Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.

Clinical Characteristics and Prognosis of Metaplastic Breast Cancer Compared with Invasive Ductal Carcinoma: A Propensity-Matched Analysis.

BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified. METHODS: We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis. RESULTS: The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, p = 0.1340) after PSM. CONCLUSION: Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.

Multi-institutional surgical outcomes of robotic single-port surgery: a Korean experience.

Background: The da Vinci single-port system (SPS) has been applied in several fields of surgery; however, only a few studies have reported its applications in general thoracic surgery. This retrospective study aimed to investigate the multi-institutional experiences of applications of SPS in Korea. Methods: The surgical outcomes of three institutions in Korea were collected and retrospectively reviewed. Results: A total of 39 surgeries were performed using SPS without conversion to multiport surgery. The patients included 16 males, and the mean age was 54.2±12.4 years. The most common pathological diagnoses were thymoma (18 cases) and benign cystic lesions (10 cases). The approach used for SPS was subxiphoid, subcostal, and intercostal in 26, 10, and 3 cases, respectively. All patients underwent the surgeries without postoperative complications. The median operation time and peak pain score were 121.4±45.4 min and 3.1±1.1. The median duration of in situ chest tube and hospital stay was 1.3±0.6 and 2.9±1.2 days, respectively. Conclusions: The application of SPS for general thoracic surgery was safe and feasible, whereas its applications remain limited to simple cases. To enable the widespread use of SPS surgery, alleviation of cost-related problems and technical improvement of SPS for complex procedures are required.