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アクセイ フクマク チュウヒシュ ニ タイスル cytoreductive surgery
海外では悪性腹膜中皮腫に対してcytoreductive surgery (CRS)と腹腔内温熱化学療法を含めた周術期化学療法が普及しているものの、本邦では悪性腹膜中皮腫に対する外科的治療の報告は乏しい。今回我々は当院でのCRSと周術期化学療法による悪性腹膜中皮腫に対する治療成績を報告する。2013年2月から2022年4月までの期間において、15例の悪性腹膜中皮腫に対してCRSを施行した。患者年齢の中央値は58歳(42-67)で、男性5例と女性10例であった。CRSは病変の存在する壁側腹膜と臓器切除を組み合わせて施行した。10例に対して術前化学療法を施行し、12例に対して術後化学療法を施行した。腹腔内温熱化学療法を8例に対して施行した。全生存期間の中央値は41か月であった。3年生存率57.7%で、5年生存率は34.6%であった。上皮型でperitoneal cancer index≦22であった6例については全例生存中であり、今後の長期生存が期待される結果であった。2.5cmより大きな腫瘍が遺残した場合でも術後化学療法の奏功により3年以上の生存が得られる症例も存在していた。単変量解析をおこなうも、生存に関する統計学的に有意な因子は認めなかった。手術合併症(Clavien-Dindo分類3以上)はGrade 3aが2例、Grade 3bが1例、Grade 4aが2例であった。悪性腹膜中皮腫に対して、これまで日本で施行されてきた化学療法単独療法では予後不良であることが知られている。一方、今回の我々が施行したCRSと周術期化学療法の治療成績は比較的予後良好であり、合併症も許容範囲内であると考えられた。悪性腹膜中皮腫に対する海外におけるCRSと化学療法による良好な治療成績の報告があることからも、本邦でのCRSと周術期化学療法の継続と症例の集積により、体系的な治療法確立と治療成績向上が期待できるであろう。Cytoreductive surgery and perioperative chemotherapy, including hyperthermic intraperitoneal chemotherapy, the standard treatments for malignant peritoneal mesothelioma worldwide are not yet widespread in Japan. We report the surgical outcomes of cytoreductive surgery with perioperative chemotherapy for patients with malignant peritoneal mesothelioma at our institution. We encountered 15 patients who required cytoreductive surgery from February 2013 to April 2022. Their median age was 58 (range 42–67) years, and there were 5 men and 10 women. Cytoreductive surgery was performed by combining extensive peritoneal resection and the resection of various organs. Ten patients underwent neoadjuvant chemotherapy. Hyperthermic intraperitoneal chemotherapy was performed in 8 patients, and 12 patients received postoperative systemic chemotherapy. The median overall survival period was 41 months for all patients. After the cytoreductive surgery, the 3- and 5-year survival rates were 57.7% and 34.6%, respectively. All six patients with epithelial-type peritoneal mesothelioma with a peritoneal cancer index of ≤22 are alive, with expected long-term survival. Furthermore, among patients with a cytoreduction completeness of 3, which indicates residual tumors of >2.5 cm in diameter, long-term survival was achieved in those who responded to chemotherapy. In the univariate analysis, no significant factor was identified for overall survival. For malignant peritoneal mesothelioma, the treatment outcome of chemotherapy alone, which is the standard treatment in Japan, is known to be poor. This study demonstrated that cytoreductive surgery with chemotherapy achieved better outcomes than known reports in Japan. The results of cytoreductive surgery with chemotherapy from across the world may improve treatment outcomes in Japan.departmental bulletin pape
Shiga Idai News Vol.34 (2023 Spring)
特 集 : 一燈照隅 ~一隅を照らす人々 ~
・若鮎遡上会実行委員会 / 医学科3年山口 瑠心さん(実行委員長)
・リレー・フォー・ライフ・ジャパン滋賀医科大学実行委員会 / 医学科4年 : 上原 希さん(実行委員長)
・滋賀テックプラングランプリ特別賞受賞者 / 医学科5年 : 石山 博章さん
・第3回創生アイデアコンテスト優秀賞受賞者 / 医学科2年 : 松山 峻大さん
・厚生労働大臣表彰を受賞 / 小児発達支援学部門 : 竹内特任教授
・ワクチン接種への貢献に対し、滋賀県から感謝状を受領
・令和4年度滋賀県救急医療功労者知事表彰受賞 / 救急・集中治療部 : 辻田准教授
・谷特任教授、山田特任准教授、仲客員教授が令和4年度科学技術分野の文部科学大臣表彰科学技術賞を受賞
食事による循環器疾患リスク予測ツールの一般公開 : NIPPON DATA研究より
看護学教育の新たな挑戦 : Virtual Reality(VR)を活用した実践・体験的学習
産学官連携により、6つの共同研究講座が新設
活動実績ダイジェスト
滋賀医科大学は開学50周年を迎えますothe
ホウゴウ フゼン ニヨル キョウクウナイ センパ ニ カンリュウ リョウホウ オ シコウシタ 1レイ
胃全摘術後に縫合不全を発症すると唾液や腸液などの消化液が漏出するが,稀に胸腔内に穿破することがある.今回,われわれは縫合不全による胸腔内穿破を胸腔内の穿刺ドレナージと洗浄で保存的に治療し,再手術を回避できたので報告する.
症例は48歳,男性.食道胃接合部癌に対して開腹下に胃全摘術を施行した.術後3日目に急激な呼吸困難を認めた.全身状態が悪く胃X線透視検査が困難であった.そのためガストログラフィン内服直後にCT撮影を施行し,縫合不全による左胸腔内穿破と診断した.穿刺ドレナージと生理食塩水の洗浄で保存的に治療し,術後25日目に縫合不全は治癒していることを確認した.
胃全摘術後の縫合不全による胸腔内穿破の報告は少なく,再手術をするか穿刺ドレナージをするか議論の余地がある.自験例では穿刺ドレナージと洗浄で保存的に治療し再手術を回避することができた.ただし,胸腔内は腹腔内に比べて適切なドレナージと瘻孔形成が不利な条件下にあるため,手術を施行するタイミングを逸しないよう慎重に経過をみる必要があると考えられた.Intestinal fluid could leak into the abdominal cavity after total gastrectomy; however, in rare cases intestinal fluid could leak into the thoracic cavity. We report a case where an intrathoracic puncture caused by leakage was treated conservatively using intrathoracic drainage and saline perfusion lavage.
A 48-year-old man with an esophagogastric junction cancer underwent open total gastrectomy. Three days postoperatively, the patient had sudden respiratory failure. Computed tomography was performed after administering oral gastrografin. The patient was diagnosed with an intrathoracic perforation caused by leakage. The intrathoracic fluid collection was drained and the thoracic cavity perfused with saline. The patient recovered fully 25 days after operation.
There are few reports of cases of intrathoracic leakage after total gastrectomy. Such cases should be followed-up closely as they are likely to become severe. Furthermore, reoperation can be avoided by drainage and saline perfusion lavage.departmental bulletin pape
Relationship of Higher-level Functional Capacity With Long-term Mortality in Japanese Older People : NIPPON DATA90
application/pdfBackground:
Basic and instrumental activities of daily living (BADL and IADL, respectively) are known predictors of mortality. However, the relationship between higher-level functional capacity (HLFC) and mortality and related sex differences have rarely been investigated.Methods:
A prospective population-based cohort study was conducted in 1,824 older residents (≥65 years) with independent BADL from 300 randomly selected areas in Japan from 1995, and the participants were followed up until 2010. Using the Cox proportional hazards model, the relationship between HLFC and mortality risk was investigated, with adjustment for possible confounders. HLFC was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Baseline data were collected using a questionnaire or by home-visit interviews.Results:
During an average 12.2-year follow-up, all-cause death was observed in 836 (45.8%) participants. Impaired HLFC was significantly associated with mortality (hazard ratio [HR] 1.37; 95% confidence interval [CI], 1.13-1.65). Lower social role was significantly associated with higher mortality risk in men (HR 1.38; 95% CI, 1.13-1.68). Lower IADL and intellectual activity were significantly associated with higher mortality risk in women (HR 1.50; 95% CI, 1.15-1.95 and HR 1.46; 95% CI, 1.19-1.79, respectively). The relationship between HLFC and mortality risk showed a similar tendency among cardiovascular diseases, stroke, cancer, and pneumonia.Journal ArticleConclusion:
Impaired HLFC was associated with a high risk of all-cause mortality among community-dwelling older people with independent BADL. In particular, social role in men and IADL and intellectual activity in women were associated with long-term mortality risk.journal articl
Oncogenic epidermal growth factor receptor signal-induced histone deacetylation suppresses chemokine gene expression in human lung adenocarcinoma
application/pdfEpidermal growth factor receptor (EGFR)-mutated (mt) lung adenocarcinoma (LA) is refractory to immune checkpoint inhibitors (ICIs). However, the mechanisms have not been fully elucidated. CD8+ T cell infiltration was significantly lower in EGFR-mt than in EGFR-wild-type LA, which was associated with suppression of chemokine expression. Since this T cell-deserted tumor microenvironment may lead to the refractoriness of ICIs against EGFR-mt LA, we investigated the mechanism by focusing on the regulation of chemokine expression. The expression of C-X-C motif ligand (CXCL) 9, 10 and 11, which constitute a gene cluster on chromosome 4, was suppressed under EGFR signaling. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) revealed open chromatin peaks near this gene cluster following EGFR-tyrosine kinase inhibitor (TKI) treatment. The histone deacetylase (HDAC) inhibitor recovered the expression of CXCL9, 10 and 11 in EGFR-mt LA. Nuclear HDAC activity, as well as histone H3 deacetylation, were dependent on oncogenic EGFR signaling. Furthermore, the Cleavage Under Targets and Tagmentation (CUT & Tag) assay revealed a histone H3K27 acetylation peak at 15 kb upstream of CXCL11 after treatment with EGFR-TKI, which corresponded to one of the open chromatin peaks detected by ATAC-seq. The data suggest that EGFR-HDAC axis mediates silencing of the chemokine gene cluster through chromatin conformational change, which might be relevant to the ICI resistance by creating T cell-deserted tumor microenvironment. Targeting this axis may develop a new therapeutic strategy to overcome the ICI resistance of EGFR-mt LA.Journal Articlejournal articl
Feasibility of Microwave Scissors-Based Off-Clamp Laparoscopic Partial Nephrectomy in a Porcine Model.
Objectives:
To assess the feasibility of off-clamp laparoscopic partial nephrectomy using microwave scissors.
Methods:
We performed transperitoneal laparoscopic partial nephrectomy, without hilar clamping or renorrhaphy, using only microwave scissors for renal resection in a porcine model. For each kidney, 2 types of procedures were performed: a middle pole resection excising an area of 2-cm diameter and approximately 1-cm depth and a lower pole resection at the level of the lower polar line. The renal calyces exposed during renal resection were sealed and transected using microwave scissors. After 3 days of follow-up, the pigs were reoperated to inspect for postoperative complications. Euthanasia was performed to collect the remaining kidneys for histopathological examination.
Results:
Ten procedures were successfully performed, without hilar clamping or suturing of the renal calyces and parenchyma, in 5 kidneys from 3 pigs. The median resecting time, blood loss, and lateral thermal injury were 23.2 min, 47.1 mL, and 6.8 mm in the middle pole resection, and were 15.1 min, 26.5 mL, and 6.9 mm in the lower pole resection, respectively. No complications were noted during reoperation, such as postoperative hemorrhage and major urine leakage. Extravasation occurred in 2 middle pole resections and 3 lower pole resections during retrograde pyelogram. Hematoxylin and eosin staining revealed thermal injury characterized by tissue microwave fixation in the near zone and acute coagulative necrosis in the intermediate zone.
Conclusions:
Microwave scissors-based off-clamp laparoscopic partial nephrectomy is feasible in pigs and can be used for clinical applications.journal articl
Detection of BRAF V600E mutation in radiological Langerhans cell histiocytosis-associated neurodegenerative disease using droplet digital PCR analysis
Langerhans cell histiocytosis-associated neurodegenerative disease (LCH-ND) is the most serious late complication secondary to LCH and is gradually progressive, destructive, and irreversible. Detection of the BRAF V600E mutation in peripheral blood mononuclear cells (PBMCs), even in the absence of active LCH lesions, is considered a sign of clinical LCH-ND, presenting with both abnormal imaging findings and neurological symptoms. However, the detection of the BRAF V600E mutation in PBMCs of patients with asymptomatic radiological LCH-ND (rLCH-ND) without active LCH lesions who present only with abnormal imaging findings is unknown. In this study, we analyzed the BRAF V600E mutations in PBMCs and cell-free DNA (cfDNA) of patients with rLCH-ND without active LCH lesions (n = 5) using a droplet digital polymerase chain reaction (ddPCR) assay. The BRAF V600E mutation in PBMCs was detected in three out of five (60%) cases. The mutant allele frequencies in the three positive cases were 0.049%, 0.027%, and 0.015%, respectively. However, the cfDNA BRAF V600E mutation remained undetected in all patients. Detection of the BRAF V600E mutant allele in PBMCs may be helpful in identifying asymptomatic rLCH-ND in patients at high risk for developing LCH-ND, including those with relapses at CNS risk sites or central diabetes insipidus.Journal Articlejournal articl
General anesthetic binding mode via hydration with weak affinity and molecular discrimination: General anesthetic dissolution in interfacial water of the common binding site of GABAA receptor
application/pdfThe GABAA receptor (GABAAR) is a target channel for the loss of awareness of general anesthesia. General anesthetic (GA) spans a wide range of chemical structures, such as monatomic molecules, barbital acids, phenols, ethers, and alkanes. GA has a weak binding affinity, and the affinity has a characteristic that correlates with the solubility in olive oil rather than the molecular shape. The GA binding site of GABAAR is common to GAs and exists in the transmembrane domain of the GABAAR intersubunit. In this study, the mechanism of GA binding, which allows binding of various GAs with intersubunit selectivity, was elucidated from the hydration analysis of the binding site. Regardless of the diverse GA chemical structures, a strong correlation was observed between the binding free energy and total dehydration number of the binding process. The GA binding free energy was more involved in the binding dehydration and showed molecular recognition that allowed for the binding of various GA structures via binding site hydration. We regarded the GA substitution for the interfacial water molecule of the binding site as a dissolution into the interfacial hydration layer. The elucidation of the GA binding mechanism mediated by hydration at the GABAAR common binding site provides a rationale for the combined use of anesthetics in medical practice and its combination adjustments via drug interactions.Journal Articlejournal articl
The efficacy of adjuvant chemotherapy on the survival of early stage endometrial cancer
Objective:
No consensus exists on the adjuvant chemotherapy for the International Federation of Gynecology and Obstetrics (FIGO) Stage I-II endometrial cancer with risk factors for recurrence. This study evaluated adjuvant chemotherapy's efficacy in improving these patients' survival.
Study design:
We conducted a retrospective chart review of patients with FIGO Stage I-II endometrial cancer with recurrence risk factors. The patients received no adjuvant therapy at the National Cancer Center Hospital (NCCH) but received platinum-based chemotherapy at Shiga University of Medical Science (SUMS).
Results:
Six hundred thirty-eight patients with endometrial cancer were identified. Of these, 118 met the inclusion criteria, 321 were excluded from NCCH, while 49 met the inclusion criteria, and 150 were excluded from SUMS. Multivariate analyses of age, surgery, para-aortic lymphadenectomy, omentectomy, histological type, myometrial invasion, cervical stromal invasion, and adjuvant therapy revealed that in patients aged > 60 years with type II histology, the outer half of myometrial invasion, cervical stromal invasion, and positive peritoneal cytology had significantly worse recurrence-free survival (RFS) rates, and patients aged > 60 years with type II histology, outer half of myometrial invasion, and positive peritoneal cytology had significantly worse overall survival (OS) rates. Patients that received adjuvant chemotherapy showed equivalent effects on RFS (hazard ratio [HR] = 2.13; 95% confidence interval [CI] = 0.82-5.53) and worse on OS ([HR = 5.20; 95 %CI = 1.26-21.50) than patients who did not.
Conclusion:
This study did not show that adjuvant chemotherapy for FIGO Stages I-II endometrial cancer with recurrence risk factors has survival benefit. Further large-scale studies are necessary to validate our findings.journal articl
Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery
Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017-March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann-Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p < 0.05). The multiple linear regression analysis indicated that the CYP2D6 polymorphism was a prediction factor of the high NRS-AUC levels in Days 0-7 (β = 9.52, 95% CI 1.30-17.7). In IM patients, the analgesic effect of tramadol was significantly reduced one week after orthopedic surgery in clinical practice. Therefore, dose escalation of tramadol or the use of alternative analgesic medications can be recommended for IM patients.journal articl