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Background We investigated the relationship between the loaded pressure and flow rate in various catheters and the entire infusion line including the catheters, in several infusion solutions and packed red blood cells. Methods We connected the infusion line and catheter to the infusion solution and used an outer pressure bag or a compressor to pressurize the infusion solution bag to a pressure within the clinical (up to 450 mm Hg) or higher range (up to 1050 mm Hg). We approximated the relationship between the loaded pressure and flow rate in the entire infusion line including the catheter, versus the catheter alone, as a power function and compared the power numbers. Results In the clinical pressure range of normal saline, the power numbers of the entire infusion line for the 24-, 22-, 20-, and 18-gauge catheters were 0.76, 0.82, 0.81, and 0.86, respectively, while those for the catheter alone were 0.67, 0.63, 0.56, and 0.44, respectively. In the higher pressure range of normal saline, the power numbers of the entire infusion line for the 24-, 22-, 20-, and 18-gauge catheters were 0.68, 0.70, 0.71, and 0.73, respectively, while those for the catheter alone were 0.62, 0.61, 0.59, and 0.58, respectively. As the power number of the entire infusion line was closer to 1.00 than the values of the catheter, the relation between the loaded pressure and the flow rate was more linear in the entire infusion line than that in the catheter. Similar results were obtained using packed red blood cells and 40% glycerin mixture in normal saline. Conclusions Regardless of the type of infusion solution or transfusion, the pressure-flow relationship in the catheter was nonlinear and not directly proportional. However, within the clinical pressure range (up to 450 mm Hg), the relationship between the flow rate and pressure in the entire infusion line was almost linear and proportional.

Opioid inhibition of nociceptive stimuli varies in individuals and is difficult to titrate. We have reported the vascular stiffness value (K) as a standard monitor to quantify sympathetic response with high accuracy. On the contrary, among individuals, a considerable variation in the rate of change in K for constant pain has been observed. In this study, we proposed a new index, the minimum stimulus intensity value that evoked the response on K (MECK: Minimum Evoked Current of K), and evaluated its accuracy in predicting sympathetic response to nociceptive stimuli under constant opioid administration. Thirty patients undergoing open surgery under general anesthesia were included. After anesthetic induction, remifentanil was administered at a constant concentration of 2 ng/ml at the effect site followed by tetanus stimulation. MECK was defined as the minimal current needed to produce a change in K. MECK significantly (P BP). Bland–Altman plot analysis using the predicted ROCBP calculated from MECK and the measured ROCBP showed that the prediction equation for ROCBP was highly accurate. This study showed the potential of MECK to predict blood pressure change during surgical incision under opioid analgesia.Clinical trial registration Registry: University hospital medical information network; Registration number: UMIN000041816; Principal investigator's name: Satoshi Kamiya; Date of registration: July 9th, 2019.

Malignant hyperthermia (MH) is a severe hypermetabolic disorder associated with dysregulation of calcium homeostasis and is triggered by inhalational anesthetics (isoflurane, sevoflurane, desflurane) and a depolarizing muscle relaxant (succinylcholine). We report the case of a 16-day-old infant undergoing laparoscopic surgery. The patient developed hyperthermia and hypercarbia with muscle rigidity. After the diagnosis of MH, dantrolene was administered with sufficient hydration. The patient was transferred to the pediatric intensive care unit for monitoring and treatment of acute renal injury due to myoglobinuria. Subsequently, two variants of the ryanodine receptor 1 (RYR1) gene were identified in the patient as the mutation point at c.1589G > A p.Arg530His and c.1841G > T p.Arg614Leu, which are known to be associated with MH. This was a rare case of MH in a 16-day-old infant that might be related to two RYR1 mutations inherited from the parents.

Resumo Historico Nausea e Vomito no Pos‐Operatorio (NVPO) e um evento adverso frequente da anestesia geral. Varias classes de antiemeticos, incluindo antagonistas do receptor 5‐Hidroxitriptamina3 (5‐HT3) e antagonistas do receptor da Neurocinina‐1 (NK‐1), tem sido utilizados para tratar a NVPO. Objetivo Comparar o efeito antiemetico dos antagonistas do receptor NK‐1, incluindo o fosaprepitanto. Fontes de dados Foram utilizadas bases de dados on‐line (PubMed, MEDLINE, Scopus, The Cochrane Library). Criterios de elegibilidade do estudo, participantes e intervencoes Foram incluidos Estudos Clinicos Randomizados (ECR) realizados em pacientes acima de 18 anos classificacao ASA I a III, com o objetivo de avaliar a eficacia de antiemeticos que incluissem antagonistas do receptor NK‐1 e antagonistas do receptor 5‐HT3, e que comparassem a incidencia de NVPO. Metodos de avaliacao e sintese do estudo Todas as avaliacoes estatisticas foram realizadas por abordagem de efeito aleatorio e foram calculadas razoes de chances e Intervalos de Confianca de 95%. Resultados As doses de 40 mg e 80 mg de aprepitanto reduziram significantemente a incidencia de vomito no periodo de 0 a 24 horas pos‐operatorias (razao de chances [OR = 0,40]; Intervalo de Confianca de 95% [95% IC] 0,30‐0,54; p Limitacoes Os fatores de risco para NVPO nao foram analisados, ECRs usando multiplos antiemeticos foram incluidos, ECRs para fosaprepitanto tinham amostras pequenas, podendo haver algum vies. Conclusoes e implicacoes dos principais achados Aprepitanto e fosaprepitanto podem ser drogas antiemeticas profilaticas efetivas para vomito no pos‐operatorio. No entanto, sao necessarios mais estudos para elaboracao de meta‐analises de melhor qualidade. Numero de registro da revisao sistematica CRD42019120188.

Purpose This study aimed to evaluate whether the three ryanodine receptor type 1 (RYR1) variants (p.Ser2345Thr, p.Ser2345Arg, and p.Lys3367Arg) which we identified in Japanese malignant hyperthermia (MH) patients with a clinical grading scale rank of 6 were causative for MH. Methods We prepared human embryonic kidney (HEK)-293 cells transfected with wild-type RYR1 or one of the RYR1 variants, along with myotubes cultured from muscle pieces. Calcium kinetics were examined by calculating the 340/380-nm ratio under various caffeine and 4-chloro-m-cresol (4CmC) concentrations with the ratiometric dye Fura-2 AM. Half-maximal effective concentration (EC50) values were calculated from dose-response curves. Statistical analysis was based on one-way analysis of variance with a Dunnett's multiple comparison test, using a P value Results In functional analysis using HEK-293 cells, we found significant reductions in the EC50 of p.Ser2345Thr and p.Ser2345Arg in comparison with wild-type RYR1 (P 0.999 for 4CmC). On the other hand, functional analysis using myotubes showed significant differences in the EC50 values for all variants (P Conclusions p.Ser2345Thr and p.Ser2345Arg appear capable of causing a calcium metabolism disorder that leads to the onset of MH, and p.Ser2345Arg can be considered as a diagnostic mutation, because it meets the European Malignant Hyperthermia Group criteria. However, patients with p.Lys3367Arg might have mutations in genes other than RYR1 that are capable of causing MH.

Introduction For successful pulmonary segmentectomy, the identification of boundaries between segments is important. Previous measures include tracing the intersegmental vessels by staining with a dye via the affected pulmonary artery or bronchus and inflating with oxygen via a high frequency ventilator. However, problems with these methods have been reported. Aim We developed a novel method using a manual jet ventilator (MJV) and investigated its efficacy in identification of the pulmonary intersegmental plane. Material and methods Patients underwent MJV for pulmonary segmentectomy in the period from January 2013 to December 2017 at our institution. The patients' characteristics, resected segments, availability of clear resection planes, and complications associated with MJV from medical records were investigated. A questionnaire survey was conducted with the surgeons on the effectiveness of lung segment identification using MJV. Results Of 199 cases of planned pulmonary segmentectomy, 171 cases with descriptions of identified intersegmental planes were analyzed. Of these, 152 (89%) cases showed a clear boundary. There were 19 cases where the exact boundaries were not clearly identified, but segmentectomy was still performed. Furthermore, we found that identification of the right upper lobes was difficult (p = 0.0028). A subjective questionnaire was answered by the 12 surgeons who performed the procedures. All 12 responded that MJV was very effective or effective regarding clarity, safety, shorter identification time, and shorter resection time. Conclusions MJV enabled surgeons to more easily and safely identify the pulmonary intersegmental plane, thereby suggesting that MJV has clinical significance during pulmonary segmentectomy.

Background Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p +/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p +/− mice. Conclusions Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice.

Introduction: Cardiac hypertrophy leading to heart failure is one of the critical causes of morbidity and mortality. Although social interest in treatment and prevention of cardiovascular disease is high, sufficient outcome has not been obtained yet. Chlorogenic acid (CGA) is one of the most abundant phenolics in plants, and is called caffeic acid. Recently, the cardioprotective effects of CGA which ameliorate isoproterenol-induced hypertrophy in vitro research have been reported. However, it has not been elucidated whether CGA affects cardiac hypertrophy in vivo models with TAC. Hypothesis: We assessed the hypothesis that the administration of CGA has protective effect on TAC-induced cardiac hypertrophy. Methods: We used mouse models of cardiac hypertrophy induced by TAC for four weeks. Mice were randomly assigned to sham, TAC, and TAC+CGA groups. CGA was administered at dose of 40mg/kg intraperitoneally once a day for four weeks after the TAC operation. cardioprotective effect was investigated by echocardiography and histological analysises. In addition, immunoblot and metabolome analysises and biomedical assays were conducted in excised hearts. Statistical analysis was performed by one-way ANOVA. All data are expressed as mean ± SD. Statistical significance was defined as P < 0.05. Results: We evaluated sham group (n=8), TAC group (n=7), TAC+CGA group (n=7) four weeks after TAC operation. TAC group showed an increase of heart weight, which was attenuated by CGA (120.3±9.3mg, 148.8±9.0mg, 126.6±6.2mg, p Conclusion: In conclusion, the present study revealed that CGA administration ameliorates pressure overload-induced cardiac hypertrophy in rodent model. As a key factor, expression of inflammatory cytokines and modulation of glucose metabolism were observed.

Background Acute onset paraplegia after endovascular aneurysm repair (EVAR) is a rare but well-known complication. We here show a 79-year-old woman with paraplegia caused by static and dynamic spinal cord insult not by ischemia after EVAR. Case presentation The patient underwent EVAR for abdominal aortic aneurism under general anesthesia in the supine position. She had a medical history of lumbar canal stenosis. After the surgery, we recognized severe paraplegia and sensory disorder of lower limbs. Although the possibility of spinal cord ischemia was considered at that time, postoperative magnetic resonance imaging (MRI) revealed burst fracture of vertebra and compressed spinal cord. Conclusions Patients with spinal canal stenosis can cause extrinsic spinal cord injury even with weak external forces. Thus, even after EVAR, it is important to consider extrinsic factors as the cause of paraplegia.

BACKGROUND It is unclear whether the doses of opioids and the routes of administration used for postoperative analgesic management are associated with delirium. We aimed to compare the incidence of postoperative delirium (POD) between intravenous patient-controlled analgesia (IVPCA) and patient-controlled epidural analgesia (PCEA) in patients who underwent postoperative analgesic management using opioids. METHODS We retrospectively investigated surgical patients (n=3,324) who received patient-controlled analgesia (PCA). Morphine was used for IVPCA, and fentanyl and ropivacaine were used for PCEA. The patients' background characteristics, perioperative management, presence of POD, and postoperative analgesia technique after IVPCA (n=1,184) or PCEA (n=2,140) were assessed. We divided the patients into IVPCA and PCEA groups and compared the incidence of POD by propensity score matching. We used the independent t-test for comparisons between the groups, and P

Coronary heart disease is a major global health concern. Further, severity of this condition is greatly influenced by myocardial ischemia/reperfusion (I/R) injury. Branched-chain amino acids (BCAAs) have cardioprotective effects against I/R via mammalian target of rapamycin (mTOR) activity, wherein Leu is considered to particularly regulate mTOR activation. However, the mechanism underlying cardioprotective effects of Leu via mTOR activity is not fully elucidated. Here, we aimed to study the signaling pathway of cardioprotection and mitochondrial function induced by Leu treatment.Cardiac myocytes isolated from adult male Wistar rats were incubated and exposed to simulated I/R (SI/R) injury by replacing the air content. Cardiac myocytes were treated with Leu and subsequently, their survival rate was calculated. To elucidate the signaling pathway and mitochondrial function, immunoblots and mitochondrial permeability transition pore were examined. Cell survival rate was decreased with SI/R but improved by 160 μM Leu (38.5 ± 3.6% vs. 64.5 ± 4.2%, respectively, p 0.001). Although rapamycin (mTOR inhibitor) prevented this cardioprotective effect induced by Leu, wortmannin (PI3K inhibitor) did not interfere with this effect. In addition, we indicated that overexpression of Opa-1 and mitochondrial function are ameliorated via Leu-induced mitochondrial biogenesis. In contrast, knockdown of Opa-1 suppressed Leu-induced cardioprotection.Leu treatment is critical in rendering a cardioprotective effect exhibited by BCAAs via mTOR signaling. Furthermore, Leu improved mitochondrial function.

Background. We investigated the potential safety of remimazolam and propofol in malignant hyperthermia- (HM-) susceptible patients using ryanodine receptor 1- (RYR1-) expressing human embryonic kidney- (HEK-) 293 cells. Methods. We compared the enhanced responsiveness of HEK-293 cells expressing wild-type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC50; i.e., the concentration required to reach half-maximal activation) using an unpaired two-tailed t -test while a P < 0.05 was considered significant. Results. Remimazolam and propofol did not promote the caffeine-induced increase in intracellular Ca2+ levels in HEK-293 cells expressing mutant RYR1 even with exposure to approximately 100-fold the clinically used concentration. In wild-type RYR1, EC50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM ( P = 0.76 ) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively ( P = 0.83 ). In mutant RYR1, EC50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively ( P = 0.63 ) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively ( P = 0.73 ). Remimazolam and propofol increased intracellular Ca2+ levels in a concentration-dependent manner, but the effect was not enhanced by RYR1. EC50 values of remimazolam with non-RYR1 vs. wild-type RYR1 were 1.00 mM vs. 0.92 mM, respectively ( P = 0.91 ) while those of propofol were 1.09 mM vs. 1.05 mM, respectively ( P = 0.84 ). Conclusions. The increase in intracellular Ca2+ concentration caused by remimazolam or propofol was not considered an RYR1-mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH-susceptible patients with RYR1-mutation without causing MH and may be safely substituted for an MH-triggering anesthetic when RYR1-mediated MH occurs.

Background: Postoperative Nausea and Vomiting (PONV) is a common complication of general anesthesia. Several kinds of antiemetics, including 5-Hydroxytryptamine3 (5-HT3) receptor antagonists, and Neurokinin-1 (NK-1) receptor antagonists have been used to treat PONV. Objectives: To compare the antiemetic effect of NK-1 receptor antagonists, including fosaprepitant. Data sources: Online databases (PubMed, MEDLINE, Scopus, The Cochrane Library databases) were used. Study eligibility criteria, participants, and interventions: Randomized Controlled Trials (RCTs) performed in patients over 18 years with ASA-PS of I‒III, aimed to assess the efficacy of antiemetics including NK-1 receptor antagonists and 5-HT3 receptor antagonists, and compared the incidence of PONV were included. Study appraisal and synthesis methods: All statistical assessments were conducted by a random effect approach, and odds ratios and 95% Confidence Intervals were calculated. Results: Aprepitant 40 mg and 80 mg significantly reduced the incidence of vomiting 0‒24 hours postoperatively (Odds Ratio [OR = 0.40]; 95% Confidence Interval [95% CI 0.30‒0.54]; p < 0.001, and OR = 0.32; 95% CI 0.19‒0.56; p < 0.001). Fosaprepitant could also reduce the incidence of vomiting significantly both 0‒24 and 0‒48 hours postoperatively (OR = 0.07; 95% CI 0.02‒0.24; p < 0.001 and OR = 0.07; 95% CI 0.02‒0.23; p < 0.001). Limitations: Risk factors for PONV are not considered, RCTs using multiple antiemetics are included, RCTs for fosaprepitant is small, and some bias may be present. Conclusions and implications of key findings: Aprepitant and fosaprepitant can be effective prophylactic antiemetics for postoperative vomiting. However, more studies are required for higher-quality meta-analyses. Systematic review registration number: CRD42019120188. Resumo Histórico: Náusea e Vômito no Pós-Operatório (NVPO) é um evento adverso frequente da anestesia geral. Várias classes de antieméticos, incluindo antagonistas do receptor 5-Hidroxitriptamina3 (5-HT3) e antagonistas do receptor da Neurocinina-1 (NK-1), têm sido utilizados para tratar a NVPO. Objetivo: Comparar o efeito antiemético dos antagonistas do receptor NK-1, incluindo o fosaprepitanto. Fontes de dados: Foram utilizadas bases de dados on-line (PubMed, MEDLINE, Scopus, The Cochrane Library). Critérios de elegibilidade do estudo, participantes e intervenções: Foram incluídos Estudos Clínicos Randomizados (ECR) realizados em pacientes acima de 18 anos classificação ASA I a III, com o objetivo de avaliar a eficácia de antieméticos que incluíssem antagonistas do receptor NK-1 e antagonistas do receptor 5-HT3, e que comparassem a incidência de NVPO. Métodos de avaliação e síntese do estudo: Todas as avaliações estatísticas foram realizadas por abordagem de efeito aleatório e foram calculadas razões de chances e Intervalos de Confiança de 95%. Resultados: As doses de 40 mg e 80 mg de aprepitanto reduziram significantemente a incidência de vômito no período de 0 a 24 horas pós-operatórias (razão de chances [OR = 0,40]; Intervalo de Confiança de 95% [95% IC] 0,30-0,54; p < 0,001 e OR = 0,32; 95% IC 0,19-0,56; p < 0,001). O fosaprepitanto pode também reduzir significantemente a incidência de vômito tanto de 0-24 horas como no período de 0-48 horas pós-operatórias (OR = 0,07; 95% IC 0,02-0,24; p < 0,001 e OR = 0,07; 95% IC 0,02-0,23; p < 0,001). Limitações: Os fatores de risco para NVPO não foram analisados, ECRs usando múltiplos antieméticos foram incluídos, ECRs para fosaprepitanto tinham amostras pequenas, podendo haver algum viés. Conclusões e implicações dos principais achados: Aprepitanto e fosaprepitanto podem ser drogas antieméticas profiláticas efetivas para vômito no pós-operatório. No entanto, são necessários mais estudos para elaboração de meta-análises de melhor qualidade. Número de registro da revisão sistemática: CRD42019120188.

We compared the pharmacokinetics of levobupivacaine when administered intraperitoneally, subcutaneously, and intravenously in an anesthetized rat model, to estimate the toxicity risk of a local anesthetic when absorbed from the peritoneum. Thirty-two rats were anesthetized with sevoflurane. In Experiment 1, we administered 5.0 mg/kg of levobupivacaine intraperitoneally (IP) (n = 7), subcutaneously (SC) (n = 6), or intravenously (IV) (n = 6). In Experiment 2, we administered 2.5 mg/kg of levobupivacaine IP (n = 7) or SC (n = 6). Data are shown as median [range] of Experiment 1. In either of experiments, the time to reach maximum plasma concentration of levobupivacaine was shorter in the IP group than in the SC group (IP: 2 [2–5] min; SC: 5 [2–10] min; P = 0.04), and the maximum concentration of levobupivacaine did not differ between the IP and SC groups (IP: 0.45 [0.05–0.67] µg/mL; SC: 0.47 [0.21–0.62] µg/mL; P = 0.90). The area under the curve from time 0 to 120 min after levobupivacaine administration was significantly higher in the SC group than in the IP group in both experiments (IP: 0.29 [0.10–0.54] mg h/L; SC: 0.78 [0.39–0.98] mg h/L; P = 0.04). Levobupivacaine is rapidly absorbed following IP administration, but its maximum plasma concentration within 2 h following IP administration is no statistical difference as that following SC administration. On the other hand, when levobupivacaine is given subcutaneously, Tmax can exceed 1 h, so we need to be aware of local anesthetic toxicity during this period.

This study aimed to evaluate whether the three ryanodine receptor type 1 (RYR1) variants (p.Ser2345Thr, p.Ser2345Arg, and p.Lys3367Arg) which we identified in Japanese malignant hyperthermia (MH) patients with a clinical grading scale rank of 6 were causative for MH.We prepared human embryonic kidney (HEK)-293 cells transfected with wild-type RYR1 or one of the RYR1 variants, along with myotubes cultured from muscle pieces. Calcium kinetics were examined by calculating the 340/380-nm ratio under various caffeine and 4-chloro-m-cresol (4CmC) concentrations with the ratiometric dye Fura-2 AM. Half-maximal effective concentration (ECIn functional analysis using HEK-293 cells, we found significant reductions in the ECp.Ser2345Thr and p.Ser2345Arg appear capable of causing a calcium metabolism disorder that leads to the onset of MH, and p.Ser2345Arg can be considered as a diagnostic mutation, because it meets the European Malignant Hyperthermia Group criteria. However, patients with p.Lys3367Arg might have mutations in genes other than RYR1 that are capable of causing MH.

The authors have retracted this article because they did not have permission to use the data in Tables 1 and 2.

Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs. Main methods: An in vivo model of I/R injury was tested in control, mTOR+/+, and mTOR+/−. Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified. Biochemical and mitochondrial swelling assays were also performed. Key findings: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001). Significance: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect., This work was supported by JSPS KAKENHI, Japan [grant number 19K09353].

We present a case of a 74-year-old man who was a heavy smoker with a performance status of 0(Brinkman indexof 2080). In 2008, he was diagnosed with idiopathic pulmonary fibrosis and was treated with pirfenidone. During follow-up, abnormal chest shadows were observed. In May 2014, he was diagnosed with right middle lobe primary squamous cell carcinoma of the lung(C-T2aN2M1a, contralateral lung metastasis)IV a, for which chemotherapy was immediately initiated. After 3 courses of carboplatin(5 AUC, day 1)plus nanoparticle albumin-bound paclitaxel(100mg/m2, days 1, 8, and 15) treatment, the primary tumor markedly decreased in size(reduction ratio, 93.3%). Moreover, both the mediastinal lymph nodes and lung metastatic lesions disappeared, and the level of tumor marker CYFRA had decreased from 29.5 to 3.4 ng/mL. The patient then underwent thoracoscopic partial resection of the right middle lobe of the lung, as a combination of these chemotherapeutic agents with salvage surgery is the standard treatment regimen for residual middle lobe lung tumors. Subsequently, he was discharged from the hospital without complications. Three courses of the same chemotherapeutic agents were administered post-surgery. As of August 2017, the patient was alive without any recurrence during the outpatient follow-up.

A 67-year-old woman was detected stage III B adenocarcinoma of the left lung, with epidermal growth factor receptor(EGFR) -mutation. Since chest computed tomography showed enlarged lymph nodes in stations 7 and 1R-4R, radiochemotherapy was recommended. However, she declined radiochemotherapy and the chemotherapy after tumor reduction surgery was chosen. She underwent resection of the left lower lobe and lingular segment, and mediastinal lymph node dissection through a posterolateral thoracotomy by extended bronchoplasty(type C) due to the extranodal invasion of lymph nodes to the lingular segmental bronchus. At postoperative day 21, she underwent right superior mediastinal lymph node dissection through a median sternotomy. Postoperatively, she received 6 cycles of chemotherapy with carboplatin plus paclitaxel followed by gefitinib. 1.5 years later, gamma knife surgery was done for multiple cerebral metastases, followed by 4 cycles of chemotherapy with cisplatin plus pemetrexed and then erlotinib. Six years after surgery, she is surviving without any evidence of disease recurrence. Tumor reduction surgery, when followed by chemotherapy, for EGFR-mutant lung adenocarcinoma is likely to lead to long-term survival.

Some biomarkers are helpful for AD diagnosis. Although many studies on efficacy of D-dimer have been reported, there are few reports about SFMC. Therefore we conducted a retrospective comparative study of efficacy of SFMC and D-dimer for diagnosis of AD.Nineteen patients diagnosed as AD in the emergency visit were examined. Patients with cardiopulmonary arrest on arrival were excluded. These patients were classified into three patterns as follows, Stanford A or B, terms of arriving at hospital, and closing type or patent type. The value of D-dimer and SFMC were measured at the time of the first medical examination, and comparative study of both biomarkers was carried out in each groups.Background of patients were not significantly different in three studies. SFMC and D-dimer showed no significant difference between Stanford A and B. Short-terms SFMC is significantly higher than long-terms. But D-dimer showed no significant difference in each comparison. Patent type of SFMC showed higher than closing type. But D-dimer showed no significant difference between patent type and closing type.SFMC showed earlier response to AD than D-dimer. Measuring SFMC coupled with D-dimer is helpful for AD diagnosis.

Background: Right upper lobectomy with right cervical and bilateral mediastinal lymph node dissection via a median approach was performed for non-small cell lung cancer. Methods: From 1995 to 2003, 48 patients aged ≤ 70 years underwent resection of cancer in the right upper lobe, including 26 with N0, four with N1 and 18 with N2 disease. Results: Metastases to the right cervical, highest mediastinal, pretracheal and bilateral tracheobronchial lymph nodes were frequent. There were no operative or hospital deaths. Preoperative accuracy of N-factor diagnosis was only 35.4%. The overall 5-year survival rate was 58.8%. The rate for C-N2 disease (n = 18) was 42.6%, and the rate for p-N2 disease (n = 7) and p-N3 disease (n = 13) was 57.1% and 0%, respectively, using the Kaplan−Meier method. Conclusions: Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease.

〈目的〉左非小細胞肺癌において,(1) N0, N1症例に対して上縦隔上部縦隔リンパ節 (#1, 2, 3) の郭清は必要か,(2) N2症例に対する系統的拡大郭清 (両側縦隔リンパ節郭清) は予後を改善するかを考察する.〈対象・方法〉左非小細胞肺癌切除例のp N0, N1, N2症例220例を対象として, 上縦隔上部リンパ節の郭清の有無による予後と再発部位の相違, ならびにN2症例の肺葉別リンパ節転移部位, 再発部位を分析した. 〈結果〉pN0症例は114例で5生率は70.5%だった. 郭清度別の比較では, 完全郭清群が73.2%(n=27), 不完全郭清群が69.5%(n=87) で有意差を認めなかった. pN1症例は48例で5生率は45.2%, 郭清度別5生率は完全郭清群が37.9%(n=23), 不完全郭清群が52.0%(n=25) で, ともに有意差を認めなかった. p N2症例は58例で原発部位は左上葉42例, 左下葉16例だった. pN2症例の5生率は23.1%で, p N0, p N1症例に対し有意差を認めた. 原発肺葉と縦隔リンパ節の転移部位の関係をみると, 左上葉は#4, 5, 6, 左下葉は#4, 5, 7のいずれかに転移を認めた. p N2症例で, 術後再発をリンパ節だけに認めたのは左下葉が3例, 左上葉1例だった. 左下葉例は対側縦隔再発だったが, 左上葉例は患側縦隔再発だった. 〈結論〉 (1) pN0, N1症例では, 上縦隔上部リンパ節の郭清を省略できる可能性がある. (2) 左肺のp N2症例に対する系統的拡大郭清は, 下葉症例のうち#7に転移を認め,#1-4,#8, 9に転移を認めない症例でのみ予後改善に寄与する可能性がある.

縦隔リンパ節転移のみを認めた稀な原発不明腺癌の1例を経験した. 症例は35歳, 男性. 咳噺, 発熱を主訴に近医を受診し, 胸部CTにて中縦隔腫瘍の診断で当科紹介入院. 胸骨正中切開下に腫瘍摘出術を施行した. 腫瘍は径7cm大であり, 右# 2,# 3, 右# 4リンパ節が一塊となったものであった. 術中迅速病理診断は低分化型腺癌リンパ節転移であったため両側縦隔郭清を施行し右# 1リンパ節にも転移を認めた. 術後の全身検索にて明らかな原発巣を確認できなかった. 術後早期に右頸部に再発したため右頸部郭清を施行し放射線治療 (50Gy) を追加した. 再切除後27カ月間経過した現在, 再発や原発巣出現の徴候なく健在である. 本症例は稀なT0N2M0原発性肺癌が考えられ, 今後も全身検索を含めた厳重な経過観察が必要である. 縦隔リンパ節転移のみを認めた原発不明癌は本邦では自験例を含め21例であり, 完全切除により予後が向上すると考えられた.

Background. UFT a blend of uracil and Tegafur (1-[2-tetrahydrofuryl]-5 fluorouracil), molar ratio, 4 : 1 is an anti-tumor agent for oral administration that is presumed to maintain the concentration of 5-fluorouracil (5-FU) in tumor tissue. The concentration of 5-FU achieved with UFT in lymph node metastases has, however, not yet been examined; in this study we aimed to clarify the transfer of 5-FU to lymph node metastases in patients treated with UFT.

症例は38歳女性.1986年から, 両側気腫性肺嚢胞にて経過観察されていた.1995年12月, 右胸部痛, 血痰が出現し, 胸部単純X線写真にて右上葉の腫瘤陰影を認めた.経皮肺生検にて肺腺癌を疑ったが確定診断にはいたらなかった.また画像診断では, 肺癌を第一に疑ったが, 胸膜中皮腫等の胸壁由来の腫瘍も否定できなかった.胸腔鏡で肺癌胸壁浸潤と診断した後, 右上中葉, 胸壁合併切除およびR2b郭清を施行した.肺癌は気腫性肺嚢胞壁より発生し, 嚢胞内腔を充満する様に発育した低分化型腺癌で, 胸壁に浸潤しておりp-T3N0M0-stage III Aであった.併せて, 気腫性肺嚢胞に合併した肺癌の切除例自験例12例について検討した.気腫性肺嚢胞は肺癌の高危険群であり, 厳重な経過観察を行うとともに癌を疑った場合には積極的な診断が必要と思われた.

A 51-year-old man consulted our hospital with complaints of a headache and spasm of the left upper limbs in January 2007. He was diagnosed as left lung adenocarcinoma (c-T2N0M1, stage IV). His serum CEA level was 104.1 ng/mL. After the brain tumor extraction, CDDP (80 mg/m2) + GEM (1,000 mg/m2) were administered as first-line treatment, and the tumor response was PR (33.3% reduction rate), impaired liver function served to interrupt this regimen. Other chemotherapy was then conducted in the order of GEM (1,000 mg/m2) + VNR (25 mg/m2), and CBDCA (AUC=5) + DOC(60 mg/m2), and the tumor response was NC. As fourth-line treatment, S-1 (75 mg/m2, day 1-28, every 6 weeks) + CBDCA (AUC=5, day 8, every 6 weeks) was chosen. After 3 courses of the treatment, the serum CEA level normalized, a chest CT detected the left lung tumor size reduction (66.7% reduction rate), and an abdominal CT detected disappearance of the left adrenal gland tumor. In January 2008, left upper lobectomy and lymph node resection (ND2a) were performed. Histopathological examination of the lung tumor showed viable adenocarcinoma cells. Postoperatively, S-1+CBDCA also was administered in a 3-course treatment. This patient is currently continuing treatment with S-1 monotherapy with no recurrence. This case suggests that S-1+CBDCA may be an effective treatment in patients with advanced non-small-cell lung cancer even after multiple chemotherapy.

To determine if the preoperative administration of tegafur and uracil (UFT) to patients with lung adenocarcinoma could induce apoptosis.We conducted a randomized prospective study on 30 patients with lung adenocarcinoma, divided into two groups of 15 patients each. One group received UFT 600 mg/day preoperatively for 7 consecutive days and a control group received no chemotherapy or radiotherapy. The apoptotic index (AI) was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) method. Expression of Ki-67 was examined by immunohistochemical staining. The concentration of 5-fluorouracil (5-FU) in tumor tissue was measured by chemical assay.The AI of lung adenocarcinoma cells increased significantly in the UFT-treated group but not in the control group. A significant positive correlation was seen between the AI and the 5-FU concentrations in the tumor tissue.The continuous oral administration of UFT for 7 days preoperatively resulted in enhanced apoptosis and a significant positive correlation between the AI and 5-FU concentrations in lung adenocarcinoma. Therefore, it may be possible to evaluate the effects of adjuvant chemotherapy based on the AI.

Thymic cancer is a rare tumor, the optimal treatment of which remains controversial. The efficacy of induction therapy in thymic cancer is unclear. A 51-year-old man was diagnosed as having a poorly differentiated carcinoma of the thymus with lymph node metastasis (stage IVb according to the Masaoka staging system), through an echo-guided biopsy. The patient was administrered cisplatin (CDDP) combined with paclitaxel once per week for 4 weeks, under concurrent local radiation. Once a partial response was achieved, the residual tumor was completely resected, and bilateral mediastinal lymph nodes were dissected. Histopathological examination of the resected specimen showed no evidence of viable malignant cells. At present, 15 months after surgery, the patient is doing well and shows no signs of recurrence. This case demonstrates that induction chemoradiotherapy with CDDP and paclitaxel may be well tolerated and useful for patients with advanced thymic cancer.