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Background: Enhanced recovery after surgery (ERAS) pathways utilize multimodal analgesia. In pathways already utilizing incisional injection of liposomal bupivacaine (ILB), we assessed the benefit of adding intrathecal opioid analgesia (ITA)., Methods: In this randomized controlled non-inferiority trial in patients undergoing laparotomy for gynecologic malignancy, we allocated patients 1:1 to ILB alone versus ITA + ILB with 150 μg intrathecal hydromorphone. The primary endpoint was the Overall Benefit of Analgesia Score (OBAS) at 24 h following surgery. Secondary endpoints included pain scores, intravenous opioid use, and cost of care., Results: Demographic and surgical factors were balanced for 105 patients. For the primary endpoint, ILB alone was non-inferior to ITA + ILB (median OBAS at 24 h of 4 vs 4; p = 0.70). We observed a significant reduction in the need for intravenous opioids (26% vs 71%; p < 0.001) and total opioid requirements (median 7.5 vs 39.3 mg morphine equivalents, p < 0.001) in the first 24 h. Clinically relevant improvements in pain scores were identified in the first 16 h after surgery favoring ITA + ILB. Total cost of the index episode, pharmacy costs, and costs at 30 days were not statistically different., Conclusions: Using OBAS as the primary endpoint, ILB alone was non-inferior to ITA + ILB. However, important cost-neutral benefits for ITA + ILB in the first 24 h post-operatively included lower pain scores and reduced need for intravenous opioids. These early, incremental benefits of adding ITA to ERAS bundles already utilizing ILB should be considered to optimize immediate post-operative pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the TMEM132C rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, p = 0.0001; CIH group, p = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the TMEM132C rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Objectives: The aim of this prospective study was to compare perioperative opioid use in women by status of CYP2D6, a highly polymorphic pharmacogene relevant to opioid metabolism., Methods: Patients undergoing laparotomy were prospectively recruited and provided a preoperative saliva swab for a pharmacogenomic (PGx) gene panel. Postoperative opioid usage and pain scores were evaluated via chart review and a phone survey. Pharmacogenes known to be relevant to opioid metabolism were genotyped, and opioid metabolizing activity predicted by CYP2D6 genotyping. Patient and procedural factors were compared using Fisher's exact and Kruskal-Wallis tests., Results: The 96 enrolled patients were classified as ultra-rapid (N = 3, 3%), normal (58, 60%), intermediate (27, 28%), and poor (8, 8%) opioid metabolizers. There was no difference in surgical complexity across CYP2D6 categories (p = 0.61). Morphine Milligram Equivalents (MME) consumed during the first 24 h after peri-operative suite exit were significantly different between groups: ultrarapid metabolizers had the highest median MME (75, IQR 45-88) compared to the other three groups (normal metabolizers 23 [8-45], intermediate metabolizers 48 [20-63], poor metabolizers 31 [12-53], p = 0.03). Opioid requirements were clinically greater in ultrarapid metabolizers during the second 24 h and last 24 h but were statistically similar (p = 0.07). There was no difference in MME prescribed at discharge (p = 0.22) or patient satisfaction with pain control (p = 0.64) between groups., Conclusions: A positive association existed between increased CYP2D6 activity and in-hospital opioid requirements, especially in the first 24 h after surgery. This provides important information to further individualize opioid prescriptions for patients undergoing laparotomy for gynecologic pathology., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Orbital apex syndrome (OAS) is a complex condition characterized by visual loss, diplopia, and eye pain that occurs secondary to several pathological processes involving the orbital apex. We report a case of acute invasive fungal rhinosinusitis (AIFRS) associated with OAS. A 76-year-old man with left-sided visual loss, diplopia, palpebral ptosis, and headache was diagnosed with OAS secondary to Tolosa-Hunt syndrome and received systemic corticosteroid therapy from his neurologist. Owing to persistent symptoms, we opened the optic canal using a transnasal endoscopic approach for a surgical biopsy of the orbital apex lesions. Histopathological evaluation revealed numerous Aspergillus organisms in the biopsied granuloma. After surgical debridement, he received a 12-month course of voriconazole, and no recurrence of AIFRS occurred during 8-year follow-up. Patients with OAS may occasionally be prescribed corticosteroids because the clinical manifestations of AIFRS-induced OAS are similar to those observed in OAS secondary to Tolosa-Hunt syndrome, especially no nasal symptoms which is known to respond to corticosteroid therapy. Because both AIFRS-induced OAS and OAS secondary to Tolosa-Hunt syndrome induce ophthalmoplegia, proptosis, eye pain, it is sometimes difficult to differentiate these two diseases in early stage. However, corticosteroid therapy causes exacerbation of fungal infection in patients with AIFRS-induced OAS resulting in delayed accurate diagnosis and poor prognosis. AIFRS is associated with a high mortality rate ; therefore, transnasal endoscopic biopsy of orbital apex lesions before corticosteroid administration is recommended in patients with OAS. J. Med. Invest. 71 : 310-313, August, 2024.

Background: Ethmoidal arteries are at risk of accidental injury during endoscopic sinus surgery (ESS)., Aims/objectives: We aimed to examine the location of ethmoidal arteries in relation to ethmoid cells and the anterior skull base (ASB) in Japanese patients., Material and Methods: CT images of 100 sides of 50 patients were retrospectively reviewed. The location of anterior ethmoidal arteries (AEAs), middle ethmoidal arteries (MEAs) and posterior ethmoidal arteries (PEAs) in relation to ethmoidal cells and their distance from the ASB were evaluated., Results: AEAs and PEAs were present in all sides. 60% of AEAs and 9% of PEAs ran below the level of ASB. MEAs were present in 21 sides and ran below the ASB in 23.8% (5/21) of these sides. The incidence of AEAs running below the level of ASB was significantly higher in the sides with supraorbital ethmoid cells (SOECs) than in those without SOECs., Conclusion and Significance: This study revealed the position and the distance from ASB of AEAs, PEAs, and MEAs in relation to ethmoid cells in Japanese patients. In cases with SOECs, surgeons should be careful not to injure the AEAs running below the level of ASB. J. Med. Invest. 71 : 273-278, August, 2024.

Background: Surgical treatment is recommended for patients with severe allergic rhinitis (AR) refractory to medical treatment. Endoscopic posterior nasal neurectomy (PNN) is primarily performed to improve rhinorrhea in severe perennial AR, however studies on its long-term prognosis are lacking., Aims/objectives: This study aimed to investigate the long-term prognosis of PNN., Materials and Methods: A questionnaire survey was administered to 17 patients (12 men and 5 women) at least 1 year after PNN. Nasal symptoms and medications, as well as patient satisfaction with surgery at the time of survey, were scored. Furthermore, scores were compared between patients with postoperative periods of >5 years and <5 years., Results: Nasal symptoms and medication scores significantly improved after surgery. There was no significant difference between patients with a postoperative period of >5 years and <5 years in both preoperative and postoperative nasal symptoms and medication scores. No correlation was found between patient satisfaction with surgery and postoperative period., Conclusions and Significance: PNN improved nasal symptoms and medication scores in patients with severe perennial AR. Furthermore, the study results suggest that the long-term effect of PNN for perennial AR lasts for >5 years. J. Med. Invest. 71 : 62-65, February, 2024.

Purpose: To evaluate the short-term efficacy and safety of a combined mifepristone-misoprostol regimen in individuals seeking medical abortion at up to 63 days of gestational age., Methods: This open-label, multicenter, prospective study evaluated the short-term efficacy and safety of medical abortion, with the primary outcome being the abortion success rate 24 h after misoprostol administration. The participants received 200 mg of mifepristone orally and 800 μg of misoprostol buccally in the hospital/clinic 36-48 h later. Bleeding and lower abdominal pain, which are the main symptoms associated with medical abortion, were recorded., Results: The abortion success rate was 93.3% (95% confidence interval [CI]: 87.3-97.1%) within 24 h of misoprostol administration, 63.3% (95% CI: 54.05-71.94%) within 4 h, and 90.0% (95% CI: 83.18-94.73%) within 8 h. The median time from misoprostol administration to a successful abortion was 3.93 h. Bleeding was most commonly observed 0-4 h prior to the confirmation of gestational sac (GS) expulsion. The most intense lower abdominal pain occurred 0-1 h before the confirmation of GS expulsion., Conclusion: The combined regimen of mifepristone and buccal misoprostol for medical abortion showed short-term efficacy and a favorable safety profile., Competing Interests: The authors declare no Conflict of Interests for this article., (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Background The incidence of severe bacterial infections (SBIs) in infants aged ≤90 days is thought to have decreased because of widespread vaccination programs. However, relevant epidemiological data in Japan are scarce. Materials and methods This observational, single-center study investigated the epidemiology of fever in infants aged ≤90 days. SBI was defined as the presence of meningitis, urinary tract infections (UTIs), or bacteremia. Invasive bacterial infection (IBI) was defined as the presence of meningitis, bacteremic UTI, or bacteremia. We determined the incidence of UTIs, bacteremia, meningitis, SBIs, and IBIs in the following three age groups: 0-28, 29-60, and 61-90 days. We subsequently calculated the relative incidence for the groups aged 29-60 and 61-90 days, using the group aged 0-28 days as the reference group.  Results Herein, 58, 124, and 166 infants were included in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. Of the total number of patients, 15.5%, 8.9%, and 16.9% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with SBI. The relative incidences were 1 for the 0-28 days group (reference group), 0.67 for the 29-60 days group (95% confidence interval [CI], 0.39-1.15), and 1.08 for the 61-90 days group (95% CI, 0.58-2.00). Of the total number of patients, 10.3%, 3.2%, and 0.6% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with IBI. Relative incidences were 1 (reference group), 0.50 (95% CI, 0.29-0.88), and 0.28 (95% CI, 0.19-0.41) for the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. All cases of IBI were caused by Group B streptococcus (GBS), except for two cases of bacteremia, which were caused by Haemophilus influenzae .  Conclusion The incidence of SBI was similar in the 0-28 days and 61-90 days age groups. However, the incidence of IBI decreased with increasing age. The incidence of UTIs was highest in the 61-90 days age group, and that of meningitis and bacteremia decreased with increasing age., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yoshitake et al.)

Considerable individual differences have been widely observed in the sensitivity to opioids. We conducted a genome-wide association study (GWAS) in patients with cancer pain to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to individual differences in opioid analgesic requirements in pain treatment by utilizing whole-genome genotyping arrays with more than 650,000 markers. The subjects in the GWAS were 428 patients who provided written informed consent and underwent treatment for pain with opioid analgesics in a palliative care unit at Higashi-Sapporo Hospital. The GWAS showed two intronic SNPs, rs1283671 and rs1283720, in the ANGPT1 gene that encodes a secreted glycoprotein that belongs to the angiopoietin family. These two SNPs were strongly associated with average daily opioid requirements for the treatment of pain in both the additive and recessive models (p < 5.0000 × 10−8). Several other SNPs were also significantly associated with the phenotype. In the gene-based analysis, the association was significant for the SLC2A14 gene in the additive model. These results indicate that these SNPs could serve as markers that predict the efficacy of opioid analgesics in cancer pain treatment. Our findings may provide valuable information for achieving satisfactory pain control and open new avenues for personalized pain treatment.

Objective: In the present study, we examined the effects of dual sublingual immunotherapy (SLIT) with Japanese cedar pollen (JCP) and house dust mite (HDM) allergens on nasal symptoms during the peak pollen period (PPP) and in late fall (LF) in patients with allergic rhinitis (AR) sensitized to both JCP and HDM. We then compared the efficacy of dual-SLIT with JCP and HDM to that of mono-SLIT with JCP at PPP., Methods: Twenty-five bisensitized patients with AR who showed positive serum specific immunoglobulin E (IgE) against both JCP and HDM were enrolled. In dual-SLIT, 16 patients received JCP drops/tablets and HDM tablets concurrently. In mono-SLIT with JCP, nine patients received JCP drops/tablets. Nasal symptoms were scored on a 0-4 point scale., Results: The nasal scores at PPP and in LF in the bisensitized patients with AR who received dual-SLIT with JCP and HDM in 2019 were significantly lower than those in the same patients who received antihistamines only in 2018. The decrease in scores of nasal obstruction at PPP from 2018 to 2019 in patients who received dual-SLIT was significantly greater than those in patients who received mono-SLIT with JCP. Dual-SLIT was well tolerated and only had mild adverse effects., Conclusion: These findings suggest that dual-SLIT suppressed both JCP-induced seasonal and HDM-induced perennial nasal symptoms in bisensitized patients with AR. Dual-SLIT was more effective in suppressing nasal obstruction at PPP than mono-SLIT with JCP with limitation of baseline characteristics not to be controlled between the two groups, suggesting that dual-SLIT suppressed HDM-induced priming effects, thus resulting in further suppression of nasal obstruction at PPP., Level of Evidence: 3b, a case-controlled study., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Cell-free and concentrated ascites reinfusion therapy (CART) has been suggested to be able to treat malignant ascites more safely and effectively with chemotherapy because of its ability to retain serum protein and albumin. Although the characteristics of cancer types and CART and the clinical implications of combination therapy with antitumor agents are becoming widespread, there are limited reports on its efficacy and complications., Methods: In this prospective observational national post-marketing study, 128 patients with malignancies received 300 CART sessions at 22 centers. After excluding other malignancies, the patients were divided into four groups: gynecological malignancies with chemotherapy (GYC+; 18 cases and 36 times) and without chemotherapy (GYC-; 35 cases and 52 times), and gastrointestinal malignancies with chemotherapy (GIC+; 8 cases and 16 times) and without chemotherapy (20 cases and 58 times)., Results: There were significant reductions in the body weight in all groups and significant reductions in abdominal circumference and significant improvements in the diet and Eastern Cooperative Oncology Group performance status only in the GYC+ group. The total serum protein and albumin increased significantly in all groups, except for the GIC+ group, before and after CART. There was no significant difference in the presence or absence of antitumor medication., Conclusion: With CART, there were differences in the improvement of the clinical symptoms between malignancy groups. The combination of CART and antineoplastic agents may be as safe as CART alone in cases of exudative malignant ascites.