Repeated Carbon-Ion Radiation Therapy for Intrahepatic Recurrent Hepatocellular Carcinoma.

PURPOSE: This retrospective study aimed to evaluate the safety and efficacy of repeated carbon-ion radiation therapy (CIRT) in patients with intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: We reviewed patients who underwent repeated CIRT for intrahepatic recurrent HCC between 2010 and 2020. RESULTS: Forty-one patients received multiple CIRT courses for HCC. During the second course, 17 (41.5%) and 24 (58.5%) of 41 patients underwent CIRT for local recurrence (LR) and intrahepatic recurrence after the first irradiation, respectively. The median age at the first course was 76 years, and the median tumor size in all the courses was 25 mm. Throughout all CIRT courses, the prescribed dose was 52.8 to 60.0 Gy (relative biological effectiveness), which was delivered in 4 to 12 fractions. The median follow-up period after the first and second CIRT was 40 and 21 months. Median overall survival (OS) after the first and second CIRT were 80 and 27 months, respectively. The 2- and 5-year OS after the first CIRT were 87.8% and 50.1%, and the 2-year OS rate after the second CIRT was 56.0%. The 1- and 2-year local control (LC) after the second CIRT was 93.4% and 83.0%, respectively. The median progression-free survival (PFS) after the second CIRT was 11 months. There were no significant differences in the LC and PFS between patients with LR and out-of-field recurrence (P = .83; 0.28, respectively). The albumin-bilirubin scores at 3 and 6 months after the second CIRT were not significantly different from those before irradiation. According to the Common Terminology Criteria for Adverse Events version 4.0, grade 4 or greater toxicities were not observed. CONCLUSIONS: Repeated CIRT for intrahepatic recurrent HCC was safe and effective, including reirradiation for LR. OS, LC, and PFS were satisfactory, and liver function was preserved. Repeated CIRT could be considered a treatment option for intrahepatic recurrent HCC.

Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities.

In the field of chiral Brønsted base catalysis, a new generation of chiral catalysts has been highly anticipated to overcome the intrinsic limitation of pronucleophiles that are applicable to the enantioselective reactions. Herein, we reveal conceptually new chiral Brønsted base catalysts consisting of two different organobase functionalities, one of which functions as an organosuperbase and the other as the substrate recognition site. Their prominent activity, which stems from the distinctive cooperative function by the two organobases in a single catalyst molecule, was demonstrated in the unprecedented enantioselective direct Mannich-type reaction of α-phenylthioacetate as a less acidic pronucleophile. The present achievement would provide a new guiding principle for the design and development of chiral Brønsted base catalysts and significantly broaden the utility of Brønsted base catalysis in asymmetric organic synthesis.

Enantioselective Formal [3+2] Cycloaddition of Epoxides with Imines under Brønsted Base Catalysis: Synthesis of 1,3-Oxazolidines with Quaternary Stereogenic Center.

The formal [3+2] cycloaddition of epoxides and unsaturated compounds is a powerful methodology for the synthesis of densely functionalized five-membered heterocyclic compounds containing oxygen. Described is a novel enantioselective formal [3+2] cycloaddition of epoxides under Brønsted base catalysis. The bis(guanidino)iminophosphorane as a chiral organosuperbase catalyst enabled the enantioselective reaction of ß,γ-epoxysulfones with imines, owing to its strong basicity and high stereocontrolling ability, to provide enantioenriched 1,3-oxazolidines having two stereogenic centers, including a quaternary one, in a highly diastereo- and enantioselective manner.

[Effects of Various Antidepressants on Hemodynamics during General Anesthesia].

BACKGROUND: It is known that serious refractory hypotension during anesthesia may develop in some patients treated with antidepressants. However the detail of this phenomenon remains unclear. METHODS: We performed a retrospective study based on written anesthesia records from April 2011 through September 2012 (n=5,578). We picked up patients who had received various types of antidepressants. We excluded cases in which neuraxial anesthesia had been performed, and preoperative general condi- tion or performed operation had affected hemodynam- ics greatly. 91 of 5,578 patients were included. All 91 patients received general anesthesia using propofol. We checked type of antidepressants taken and use of vasopressors during anesthesia. RESULTS: Type of antidepressants taken by 91 patients had no effect on the frequency of vasopressor administration. However, 7 of 91 patients showed treatment-resistant refractory hypotension by ephed- rine and phenylephrine. Catecholamines (noradrenaline, dobutamine) were effective. Frequency of refractory hypotension was significantly higher with serotonin and noradrenaline reuptake inhibitors (SNRI) or with two combined antidepressants. CONCLUSIONS: Type of antidepressants had no effect on frequency of vasopressor administration. Treat- ment-resistant refractory hypotension by ephedrine and phenylephrine was significantly higher with SNRI or two combined antidepressants. Sympathetic nerve activity may be influenced by interaction of anesthetics and antidepressants in some patients.

Enantioselective Addition of a 2-Alkoxycarbonyl-1,3-dithiane to Imines Catalyzed by a Bis(guanidino)iminophosphorane Organosuperbase.

A chiral bis(guanidino)iminophosphorane catalyzes enantioselective addition reactions of a 1,3-dithiane derivative as a pronucleophile. The chiral uncharged organosuperbase facilitates the addition of benzyloxycarbonyl-1,3-dithiane to aromatic N-Boc-protected imines to provide optically active α-amino-1,3-dithiane derivatives, which are valuable versatile building blocks in organic synthesis.

The accuracy of non-invasively continuous total hemoglobin measurement by pulse CO-Oximetry undergoing acute normovolemic hemodilution and reinfusion of autologous blood.

BACKGROUND: Non-invasively continuous total hemoglobin (SpHb) measurement has not been assessed adequately in acute bleeding and rapid blood transfusion during surgery. Thus, we have assessed the efficacy of SpHb during both acute normovolemic hemodilution (ANH) and autologous blood transfusion (ABT). METHODS: Twenty-four patients undergoing urological and gynecological surgery were enrolled. ANH was induced by withdrawing blood of 800 g with simultaneous fluid administration. When surgical hemostasis was completed, collected blood was reinfused. Measurement of SpHb, perfusion index (PI) and real total Hb (tHb) were done before and after each 400 ml blood removal (-0, -400, -800 ml) and reinfusion (+0, +400, +800 ml). RESULTS: A Bland-Altman analysis for repeated measurements showed a bias (precision) g/dl of 1.12 (1.25), 1.43 (1.24) and 1.10 (1.23) for all data, during ANH and during ABT, respectively. Additionally, a bias (precision) increased with a reduction in tHb (g/dl): ≥10.0; 0.74 (1.30), 8.0-10.0; 1.15 (1.12) and <8.0; 1.60 (1.28). Although the difference between SpHb and tHb was almost zero before anesthesia induction, it became significant just before ANH and did not change further by ANH and ABT. Significant correlations between SpHb and tHb for all data (r = 0.75, n = 228, p < 0.001) were observed. PI slightly correlated with the difference between SpHb and tHb (r = 0.38, n = 216, p < 0.001). Furthermore, before and after induction of anesthesia, PI also correlated with the difference between SpHb and tHb (r = 0.42, n = 23, p = 0.048 and r = 0.51, n = 22, p = 0.016, respectively). CONCLUSIONS: The present data suggest that SpHb may overestimate tHb during ANH and ABT. In addition, PI and tHb levels had an impact on the accuracy of SpHb measurements.

Endogenous neuropeptide S tone influences sleep-wake rhythm in rats.

Neuropeptide S (NPS) is an endogenous peptide that exerts wakefulness promoting, analgesic, and anxiolytic effects when administered exogenously. However, it remains to be determined if endogenous NPS tone is involved in the control of the diurnal sleep-wake cycle, or spontanous behavior. In this study, we examined the effects of the NPS receptor antagonist [D-Cys((t)Bu)(5)]NPS (2 and 20 nmol, icv) on physiological sleep and spontaneous locomotor behavior. The higher dose of [D-Cys((t)Bu)(5)]NPS decreased the amount of time spent in wakefulness [control 782.5 ± 25.5 min, treatment 751.7 ± 28.1 min; p<0.05] and increased the time spent in NREMS [control 572.6 ± 17.2 min, treatment 600.2 ± 26.1 min; p<0.05]. There was no statistically significant difference in time spent in REMS. There were no behavioral changes including abnormal gross motor behavior in response to [D-Cys((t)Bu)(5)]NPS administration. Collectively these data suggest an involvement of the endogenous NPS/NPS receptor system in physiological sleep architecture.

[Rectus sheath block and transversus abdominis plane block for a patient with Lambert-Eaton myasthenic syndrome undergoing low anterior resection].

A 55-year-old male with Lambert-Eaton myasthenic syndrome underwent low anterior resection. Before anesthetic induction, his arterial blood gas analysis showed chronic hypercapnia (pH 7.404, Paco2 59 mmHg, BE 9.1). Anesthesia was induced with propofol, remifentanil and ketamine. Uneventful tracheal intubation was achieved after superior laryngeal nerve block without using muscle relaxants. Then ultrasound-guided bilateral rectus sheath block and transversus abdominis plane block were performed using 60 ml of 0.375% ropivacaine. Anesthesia was maintained with propofol, remifentanil monitoring bispectral index. Good surgical condition was maintained even without using muscle relaxants. Although only a small amount of morphine was required during the early postoperative days, his postoperative course was smooth and uneventful. The present case shows that ultrasound-guided rectus sheath block and transversus abdominis plane block are safe and useful for abdominal surgery in patients with neuromuscular disease.