ABSTRACT
Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (P<0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.
Subject(s)
Humans , Adult , Male , Female , Middle Aged , Aged , Histones/genetics , Brain Neoplasms/pathology , Proto-Oncogene Proteins B-raf/metabolism , Glioma/pathology , Astrocytoma/pathology , MutationABSTRACT
ObjectiveTo compare the effects of programmed intermittent epidural bolus （PIEB） and continuous epidural infusion （CEI） on enhanced recovery after cesarean section. MethodsTotally 120 women scheduled to undergo elective cesarean section under combined spinal and epidural anesthesia， aged 18-45 years， with single fetus， full-term pregnancy （≥37 weeks）， ASA grade II or III， were recruited， with 60 cases in each group. At the end of the surgery， after a similar epidural loading dose， patients were randomLy assigned to receive either PIEB （6 mL·h-1 beginning 30 minutes after the loading dose） or CEI （6 mL·h-1， beginning immediately after the loading dose） for the maintenance of analgesia with 0.1% ropivacaine. At 2， 6， 12， 24 and 36 h postoperatively， VAS score was used to evaluate the composite pain， and Bromage Score was used to evaluate the degree of lower extremity motor block. The time to first flatus， time to first ambulation and the satisfaction scores were also recorded. ResultsThe VAS scores at 12， 24 and 36 h postoperatively and the lower extremity motor block scores at 6， 12 and 24 h postoperatively in the PIEB group were significantly lower than those in the CEI group （P < 0.01）. The epidural analgesic dosage was less in the PIEB group than that of the CEI group （P=0.002）. The time to first flatus and time to first ambulation were significantly shorter than those in the CEI group （P < 0.05）. The satisfaction scores were significantly higher in the PIEB group than in the CEI group （P < 0.05）. There was no significant difference in the first urination time after urinary catheter removal and the length of hospital stay between the two groups （P > 0.05）. ConclusionCompared with CEI， PIEB provides better postoperative analgesia， less motor block scores， lower epidural analgesic dosage， shorter the time to first flatus and defecation and time to first ambulation， and greater patient satisfaction， which is more consistent with the ERAS concept of analgesia.