Chronic hypoxia remodels the tumor microenvironment to support glioma stem cell growth.

Cerebral organoids co-cultured with patient derived glioma stem cells (GLICOs) are an experimentally tractable research tool useful for investigating the role of the human brain tumor microenvironment in glioblastoma. Here we describe long-term GLICOs, a novel model in which COs are grown from embryonic stem cell cultures containing low levels of GSCs and tumor development is monitored over extended durations (ltGLICOs). Single-cell profiling of ltGLICOs revealed an unexpectedly long latency period prior to GSC expansion, and that normal organoid development was unimpaired by the presence of low numbers of GSCs. However, as organoids age they experience chronic hypoxia and oxidative stress which remodels the tumor microenvironment to promote GSC expansion. Receptor-ligand modelling identified astrocytes, which secreted various pro-tumorigenic ligands including FGF1, as the primary cell type for GSC crosstalk and single-cell multi-omic analysis revealed these astrocytes were under the control of ischemic regulatory networks. Functional validation confirmed hypoxia as a driver of pro-tumorigenic astrocytic ligand secretion and that GSC expansion was accelerated by pharmacological induction of oxidative stress. When controlled for genotype, the close association between glioma aggressiveness and patient age has very few proposed biological explanations. Our findings indicate that age-associated increases in cerebral vascular insufficiency and associated regional chronic cerebral hypoxia may contribute to this phenomenon.

New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

Postoperative laryngeal morbidity and intubating conditions using the McGRATH™ MAC videolaryngoscope with or without neuromuscular blockade: a randomised, double-blind, non-inferiority trial.

Tracheal intubation without neuromuscular blockade may be associated with worse intubating conditions and increased laryngeal morbidity. We hypothesised that tracheal intubation using the McGRATH™ MAC videolaryngoscope would not increase postoperative hoarseness, even without neuromuscular blockade. In this prospective, randomised, parallel-group, double-blind, non-inferiority trial, 248 patients were randomly assigned to tracheal intubation with or without neuromuscular blockade using rocuronium. Hoarseness and sore throat were evaluated at 24 h and 48 h postoperatively. The primary outcome was the incidence of hoarseness at 48 h postoperatively with a pre-defined non-inferiority margin of 10%. Hoarseness at 48 h did not differ between the non-paralysed group and the paralysed group (8.1% vs. 13.6%; absolute difference: -5.4%; 95%CI: -13.3 to 2.4). Also, no significant differences were found between the two groups for hoarseness at 24 h (22.8% vs. 27.1%) or for sore throat at 24 h (12.2% vs. 9.3%) and 48 h postoperatively (1.6% vs. 0.8%). Although more patients in the non-paralysed group showed an adducted position of the vocal cords (29.3% vs. 0%), there were no significant group differences in the ease of laryngoscopy (96.7% vs. 98.3%), Cormack grade laryngeal view 1 (97.6% vs. 96.6%) or first-pass success rate (100% vs. 100%). We conclude that when using the McGRATH MAC videolaryngoscope for tracheal intubation, the incidence of postoperative hoarseness was not inferior if neuromuscular blockade was avoided.

PRR11 immunoreactivity is a weak prognostic factor in non-mucinous invasive adenocarcinoma of the lung.

INTRODUCTION: Proline-rich protein 11 (PRR11) functions in the progression of cell cycle, and silencing the PRR11 gene in lung cancer cells results in the inhibition of cellular proliferation, cell cycle progression, cell migration, invasion and colony formation. PRR11 may therefore be a therapeutic target in lung cancer. MATERIALS AND METHODS: Microarrays of surgical specimens of non-mucinous invasive adenocarcinoma of the lung, from 346 subjects that were not given preoperative therapy, were autoimmunostained with PRR11 and, except for trace and pseudo-positivity, assessed as "positive" at any proportion and intensity. RESULTS: PRR11 immunoreactivity demonstrated a tendency to associate with an aggressive phenotype (tumor size, vascular invasion, and adjuvant therapy) and some effect on overall survival (Hazard ratio 1.51). CONCLUSIONS: PRR11 may be a weak prognostic indicator of overall survival of patients with non-mucinous invasive adenocarcinoma of the lung.

Intravenous dexmedetomidine for cesarean delivery and its concentration in colostrum.

BACKGROUND: Dexmedetomidine is a sedative agent with high α2-adrenoreceptor selectivity. We investigated intravenous dexmedetomidine administration during scheduled cesarean delivery under neuraxial anesthesia; and its concentration in the colostrum. METHODS: Twenty-seven participants having elective cesarean delivery under combined spinal-epidural anesthesia were enrolled. After delivery and cord clamping, 6µg/kg/h of intravenous dexmedetomidine was administered for 10minutes, followed by a dose of 0.7µg/kg/h until peritoneal closure. Sedation, vital signs and side effects were recorded. Blood and colostrum samples were collected from each participant at 6, 12, and 24h after dexmedetomidine administration. Samples were analysed using liquid chromatography tandem-mass spectroscopy. RESULTS: Colostrum samples were collected from 10 patients. The median [95% CI] plasma dexmedetomidine concentration was 333 [303-534] pg/ml at 0h and 19.7 [13.5-25.8] pg/ml at 6h. The colostrum concentration was 12.3 [8.1-20.1] pg/ml at 6h. The dexmedetomidine completely disappeared from both within 24h. The calculated milk-to-plasma ratio at 6h was 0.76 [0.57-0.86]. The relative infant dose was 0.034% [0.020-0.062%]. At dexmedetomidine discontinuation, the Richmond Agitation-Sedation Scale score was -2 (range,-4 to -1). During surgery, no patients complained of nausea, peritoneal irritation or afterbirth pain. CONCLUSIONS: The dexmedetomidine milk-to-plasma ratio did not exceed 1 in any participant, and the relative infant dose was very low. Maternal sedation using dexmedetomidine is unlikely to be harmful for the infant.

On the mechanism of gas adsorption for pristine, defective and functionalized graphene.

Defects are no longer deemed an adverse aspect of graphene. Contrarily, they can pave ways of extending the applicability of graphene. Herein, we discuss the effects of three types of defects in graphene including carbon deficiency, adatom (single Fe) dopants and the introduction of functional groups (carbonyl, ether group) on the NO2 gas adsorption via density functional theory methods. We have observed that introducing Fe on graphene can enhance the NO2 adsorption process. Adsorption energy calculations suggest that the enhancement in NO2 adsorption is more profound for Fe-doped mono- and tetra-vacant graphene than that for Fe doped bi- and tri-vacant graphene, which is favourable for NO2 gas capture applications. The unsaturated carbons in defected graphene as well as the oxygenated functional groups are very active to attract NO2 molecules. However, though the gas binding strength was not as high as the that found in the Fe-doped graphene structure, the relatively low NO2 gas adsorption energy is suitable for the practical gas sensors both for gas sensitivity and the sensor recovery rate factor. This theoretical study can potentially be useful for developing adsorption-based applications of graphene.

A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. METHODS: A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. RESULTS: The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. CONCLUSIONS: In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for postmenopausal Japanese women over 60 years. In terms of cost-effectiveness, the individual need for osteoporosis screening should be determined by age and clinical risk factors.

Possible Involvement of the Rat Hypothalamo-Neurohypophysial/-Spinal Oxytocinergic Pathways in Acute Nociceptive Responses.

Oxytocin (OXT)-containing neurosecretory cells in the parvocellular divisions of the paraventricular nucleus (PVN), which project to the medulla and spinal cord, are involved in various physiological functions, such as sensory modulation and autonomic processes. In the present study, we examined OXT expression in the hypothalamo-spinal pathway, as well as the hypothalamo-neurohypophysial system, which includes the magnocellular neurosecretory cells in the PVN and the supraoptic nucleus (SON), after s.c. injection of saline or formalin into the hindpaws of transgenic rats that express the OXT and monomeric red fluorescent protein 1 (mRFP1) fusion gene. (i) The numbers of OXT-mRFP1 neurones that expressed Fos-like immunoreactivity (-IR) and OXT-mRFP1 intensity were increased significantly in the magnocellular/parvocellular PVN and SON after s.c. injection of formalin. (ii) OXT-mRFP1 neurones in the anterior parvocellular PVN, which may project to the dorsal horn of the spinal cord, were activated by s.c. injection of formalin, as indicated by a significant increases of Fos-IR and mRFP1 intensity intensity. (iii) Formalin injection caused a significant transient increase in plasma OXT. (iv) OXT, mRFP1 and corticotrophin-releasing hormone mRNAs in the PVN were significantly increased after s.c. injection of formalin. (v) An intrathecal injection of OXT-saporin induced hypersensitivity in conscious rats. Taken together, these results suggest that the hypothalamo-neurohypophysial/-spinal OXTergic pathways may be involved in acute nociceptive responses in rats.

Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.

Cancer cells gain a growth advantage through the so-called Warburg effect by shifting glucose metabolism from oxidative phosphorylation to aerobic glycolysis. Hypoxia-inducible factor 1 (HIF-1) has been suggested to function in metabolic reprogramming; however, the underlying mechanism has not been fully elucidated. We found that the aberrant expression of wild-type isocitrate dehydrogenase 3α (IDH3α), a subunit of the IDH3 heterotetramer, decreased α-ketoglutarate levels and increased the stability and transactivation activity of HIF-1α in cancer cells. The silencing of IDH3α significantly delayed tumor growth by suppressing the HIF-1-mediated Warburg effect and angiogenesis. IDH3α expression was associated with the poor postoperative overall survival of lung and breast cancer patients. These results justify the exploitation of IDH3 as a novel target for the diagnosis and treatment of cancers.

Fluorescent visualisation of the hypothalamic oxytocin neurones activated by cholecystokinin-8 in rats expressing c-fos-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 fusion transgenes.

The up-regulation of c-fos gene expression is widely used as a marker of neuronal activation elicited by various stimuli. Anatomically precise observation of c-fos gene products can be achieved at the RNA level by in situ hybridisation or at the protein level by immunocytochemistry. Both of these methods are time and labour intensive. We have developed a novel transgenic rat system that enables the trivial visualisation of c-fos expression using an enhanced green fluorescent protein (eGFP) tag. These rats express a transgene consisting of c-fos gene regulatory sequences that drive the expression of a c-fos-eGFP fusion protein. In c-fos-eGFP transgenic rats, robust nuclear eGFP fluorescence was observed in osmosensitive brain regions 90 min after i.p. administration of hypertonic saline. Nuclear eGFP fluorescence was also observed in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) 90 min after i.p. administration of cholecystokinin (CCK)-8, which selectively activates oxytocin (OXT)-secreting neurones in the hypothalamus. In double transgenic rats that express c-fos-eGFP and an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene, almost all mRFP1-positive neurones in the SON and PVN expressed nuclear eGFP fluorescence 90 min after i.p. administration of CCK-8. It is possible that not only a plane image, but also three-dimensional reconstruction image may identify cytoplasmic vesicles in an activated neurone at the same time.

Solid tumor size on high-resolution computed tomography and maximum standardized uptake on positron emission tomography for new clinical T descriptors with T1 lung adenocarcinoma.

BACKGROUND: To better describe clinical T descriptors using solid tumor size (the maximum dimension of the solid component of the tumor) on high-resolution computed tomography (HRCT) and maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT). PATIENTS AND METHODS: We examined 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. Recurrence-free survival (RFS) was assessed on the basis of whole tumor size (maximum dimension of the tumor), solid tumor size, or a combination of solid tumor size and SUVmax. RESULTS: RFS based on whole tumor size was not significantly different between patients with tumors measuring ≤2 cm and 2-3 cm (P = 0.089), whereas RFS based on solid tumor size was significantly different (P < 0.0001). We divided patients into four groups on the basis of solid tumor size and SUVmax: group 1: solid tumor size ≤2 cm, SUVmax ≤1.8; group 2: solid tumor size ≤2 cm, SUVmax >1.8; group 3: solid tumor size 2-3 cm, SUVmax ≤3.6; and group 4: solid tumor size 2-3 cm, SUVmax >3.6. Groups 2 and 3 were combined because they showed similar RFS each other. RFS was significantly different among these groups: group 1 versus groups 2 + 3, P < 0.0001; groups 2 + 3 versus group 4, P = 0.019. CONCLUSIONS: Both solid tumor size on HRCT and SUVmax on FDG-PET/CT reflect prognosis well in patients with clinical stage IA lung adenocarcinoma and may support new clinical T descriptors.

Thyroid remnant ablation with 1110MBq of 131I in outpatients: measurement of effective dose to household members and establishment of safety precautions.

AIM: The aim of this study was to establish and confirm the safety of administering 1110MBq of 131I to outpatients. METHODS: Total radiation exposure from patients to household members was hypothesized from the measured dose rate at 1 m when the patient is released. Actually we also measured the effective dose to household members who assisted outpatients during the first 7 days after the administration of 131I by personal dosimeter. A list of radiation safety precautions is given to the patient and household members. Behavioral reports about the distances and times of close contact throughout the 7 days are requested of each household member. RESULTS: The effective dose measured using the personal dosimeter to all household members employing several safety precautions was confirmed to be lower than the hypothesized dose calculated using our formula. And the mean whole-body effective dose rate over the 7 days in household members was 0.05±0.08 (range, 0.05 to 0.43) mSv, which specify that radiation exposure to household members of the outpatients who have just received ablative radiation therapy must be below 5.0 mSv/event. CONCLUSION: Remnant thyroid ablation with 1110MBq for outpatients showed that the radiation doses to household members were within the recommended constraint dose according to several safety precautions. The method of returning home after remnant thyroid ablation is thought to be the most important factor that determines the effective dose to household members of outpatients.

Non-destructive evaluation of ATP content and plate count on pork meat surface by fluorescence spectroscopy.

The potential of fluorescence spectroscopy was investigated for the non-destructive evaluation of ATP content and plate count on pork meat surface stored aerobically at 15 °C during three days. Excitation (Ex) Emission (Em) Matrix of fluorescence intensity was obtained and fluorescence from tryptophan (Ex=295 nm and Em=335 nm) and NADPH (Ex=335 nm and Em=450 nm) was detected. Because tryptophan and NADPH fluorescence changed along with the growth of microorganisms, microbial spoilage on meat could be detected from fluorescence. By applying PLSR (Partial Least Squares Regression) analysis, ATP content and plate count were predicted with good determination coefficient (0.94-0.97 in calibration and 0.84-0.88 in validation).

A c-fos-monomeric red fluorescent protein 1 fusion transgene is differentially expressed in rat forebrain and brainstem after chronic dehydration and rehydration.

We have previously shown that an acute osmotic stimulation induces the expression of a c-fos and monomeric red fluorescent protein 1 (mRFP1) fusion transgene in osmosensitive rat brain areas, including the supraoptic (SON) and paraventricular nuclei (PVN). However, the effects of chronic stimuli, such as dehydration, have not been investigated. In the present study, the expression patterns of the c-fos-mRFP1 fusion gene in the forebrain and the brainstem of male and female transgenic rats were studied in seven experimental groups: ad lib. water (euhydration), water deprivation for 12, 24 or 48 h (dehydration) and water deprivation for 46 h + ad lib. water for 2, 6 or 12 h (rehydration). The number of cells that express nuclear mRFP1 fluorescence was quantified in the hypothalamus, the circumventricular organs and the brainstem. Compared to the euhydrated state, the number of transgene expressing cells significantly increased in all forebrain areas and in the rostral ventrolateral medulla after dehydration and 2 h of rehydration. In the nucleus of the solitary tract and area postrema, the number of mRFP1 fluorescent cells was markedly increased after 2 h of rehydration. Although the number of mRFP1 fluorescent cells in the organum vasculosum laminae terminalis, median preoptic nucleus and subfornical organ remained significantly increased after 6 h of rehydration, reaching control levels after 12 h of rehydration, the number of mRFP1 fluorescent cells in the SON and the PVN reached control levels after 6 h of rehydration. There were no significant differences between male and female rats. These results show that the expression of the c-fos-mRFP1 fusion gene changes in the forebrain and the brainstem not only after acute osmotic stimulation, but also after chronic osmotic stimulation. Interestingly, these studies reveal the differential activation of different neuronal groups over the time course of dehydration and rehydration.

Involvement of decreased hypoxia-inducible factor 1 activity and resultant G1-S cell cycle transition in radioresistance of perinecrotic tumor cells.

Cancer patients often suffer from local tumor recurrence after radiation therapy. Some intracellular and extracellular factors, such as activity of hypoxia-inducible factor 1 (HIF-1), cell cycle status and oxygen availability, have been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. But when, where, and how these factors affect one another and induce cellular radioresistance is largely unknown. Here, we analyzed mechanistic and spatio-temporal relationships among them in highly heterogeneous tumor microenvironments. Experiments in vitro demonstrated that a decrease in the glucose concentration reduced the transcriptional activity of HIF-1 and expression of a downstream gene for the cell cycle regulator p27(Kip1) even under hypoxic conditions. Then, the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased, significantly. Immunohistochemical analyses showed that cancer cells in perinecrotic hypoxic regions, which should be under low-glucose conditions, expressed little HIF-1α, and therefore, were mainly in S phase and less damaged by radiation treatment. Continuous administration of glucagon, which increases the blood glucose concentration and so improves glucose availability in perinecrotic hypoxic regions, induced HIF-1α expression and increased radiation-induced DNA damage. Taken all together, these results indicate that cancer cells in perinecrotic regions, which would be under low-glucose and hypoxic conditions, obtain radioresistance by decreasing the level of both HIF-1 activity and p27(Kip1) expression, and adjusting their cell cycle to the radioresistant S phase.

Biphasic action of aldosterone on Akt signaling in cardiomyocytes.

Both aldosterone and Akt signaling play pivotal roles in the pathogenesis of heart failure. However, little is known about the correlation between them. We herein investigated whether aldosterone interacts with Akt signaling in a coordinated manner in cardiomyocytes. Neonatal rat cardiomyocytes were stimulated with aldosterone for either a short (10-min) or long (24-h) time. The phosphorylation of Akt and its downstream effector, GSK3ß, were transiently increased after short-term stimulation, which was blocked by either PI3K or Na(+)/H(+) exchanger inhibitors, but not by the mineralocorticoid receptor antagonist, eplerenone. Long-term stimulation also significantly increased Akt-GSK3ß phosphorylation and this effect was reduced by eplerenone. Thus, these results suggest that aldosterone activates Akt signaling via a biphasic reaction that occurs through different cascades. To understand the significance of the rapid action of aldosterone, cardiomyocytes were exposed to hydrogen peroxide for from 10 to 60 min. A short-term aldosterone stimulation (for up to 30 min) significantly protected cardiomyocytes from oxidative stress-induced cellular damage. Eplerenone did not abrogate this beneficial effect, while a PI3K inhibitor did. Therefore, during the early phase, aldosterone has favorable effects on cardiomyocytes, partly by acute activation of a mineralocorticoid receptor-independent cascade through the Na(+)/H(+) exchanger, PI3K, and Akt. In contrast, its persistent activity produces pathological effects partly by chronic Akt activation in a mineralocorticoid receptor-dependent manner.

Phase I study of paclitaxel, cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer.

PURPOSE: We investigated the safety of triple combination therapy by addition of Paclitaxel (PTX) to Cisplatin (CDDP) and 5-fluorouracil (5-FU) combination therapy, which was considered the conventional standard therapy for patients with unresectable / recurrent gastric cancer. MATERIAL AND METHODS: The doses of PTX and CDDP were fixed at 80 and 50 mg/m2. They were administered on days 1 and 8, followed by a resting period of 20 days. 5-FU 300 mg/m2 at a maximum dose of 500 mg/m2 was administered at levels 0 and 2, respectively, and the dose was increased by 100 mg/m2 until the maximum tolerated dose (MTD). It was administered on days 1 - 5 and 8 - 12, followed by a resting period of 16 days. RESULTS: Twelve patients enrolled in this study. Of them, three patients were excluded from evaluation because treatment continuation was not feasible. There were 4 leukopenia and 7 neutropenia cases with hematological toxicity at grade 3 or higher. They were observed at all dose levels, but no case showed infection. In terms of non-hematological toxicity at grade 3 or higher, there were two patients with nausea and vomiting and two patients with diarrhea, one patient with mucositis, one patient with anorexia. All patients with non-hematological toxicity at grade 3 or higher were at level 2. The dose-limiting toxicity (DLT) was observed at level 2, and 5-FU at 400 mg (level 1) was adopted. CONCLUSIONS: We proved in this study that PTX, CDDP, and 5-FU combination chemotherapy was a safe treatment.

[Treatment of superior sulcus tumor].

We reported on 34 patients with superior sulcus non-small-cell lung cancer and clinical outcome. It is necessary to select the most appropriate approach from preoperative examination and the degree of infiltration at the chest wall. Recently, various approach and preoperative chemoradiotherapy followed by surgical resection is effective for the treatment of superior sulcus tumor (SST), we should keep challenging for radical resection in mind.