The participants were followed from September 2015 until September 2016 for evaluation of the occurrence of permanent neurological deficits.
Descriptive data analysis
Twenty-nine patients were male and 29 were female. The mean age at time of surgery was 56.6 ± 13.7 years (range: 32–80). Of the 58 patients, 35 had a primary brain tumor and 23 had a metastatic brain tumor. Among patients with primary brain tumors, 7 patients had a low-grade glioma (LGG) (World Health Organization (WHO) grade I in 1 case, WHO grade II in 6), and 28 patients a high-grade glioma (HGG) (WHO grade III in 15 cases, WHO grade IV in 13). Twelve patients had a glioblastoma, 9 an anaplastic astrocytoma, 5 a diffuse astrocytoma, 5 an anaplastic oligodendroglioma, 1 an oligodendroglioma, 1 an anaplastic oligoastrocytoma, 1 a ganglioglioma, and 1 a gliosarcoma. O(6)-methylguanine-DNA methyltransferase (MGMT) methylation was found in 12 patients, whereas isocitrate dehydrogenase 1 (IDH1) mutation was detected in 17 patients and 1p/19q codeletion in 8 patients.
Adenocarcinoma was the most common histological type among patients with metastatic brain tumors, affecting 10 patients, followed by melanoma (4 patients), undifferentiated carcinoma (2 patients), squamous cell carcinoma (2 patients), and other subtypes (5 patients).
The primary sites in patients with metastatic tumors were as follows: lung cancer in 10 cases, melanoma in 4, upper gastrointestinal tract tumors in 2, ovarian cancer in 1, urinary tract cancer in 1, and unknown in 5 cases.
Seventeen patients had had previous treatment with radiotherapy, whereas 20 patients had received chemotherapy prior to surgery. Among the patients with primary brain tumors who had received chemotherapy prior to surgery, 10 were treated with temozolomide, whereas only one patient had received lomustine (CCNU).
The main tumor location was frontal in 30 cases, temporal in 15, and parietal in 5, in the basal ganglia in 3 cases, and in other locations in 5. Twenty-one patients had left-sided tumors, 26 right-sided tumors, and 11 bilateral tumors.
Fifty-six of the 58 surgical procedures were performed by eight board-certified neurosurgeons. In detail, senior surgeons with a mean experience of 17.5 years (range 14–25 years) performed 43 surgeries, while surgeons with an intermediate experience level (8.5 years, range 7–10 years) performed 13 surgeries. Two of the 58 surgical procedures were performed by chief residents under supervision of one of the above-mentioned board-certified neurosurgeons.
The mean duration of surgery was 2.71 ± 0.87 h in the rIPC group and 2.62 ± 0.9 h in the control group. Forty-four patients were classified as American Society of Anesthesiologists Physical Status (ASA PS) 1 or 2 (low risk), and 9 as ASA PS 3 (intermediate risk). An ASA PS classification was not available for 5 patients. The use of intraoperative neurophysiological monitoring was similar in both groups (20 patients in the rIPC group vs. 19 patients in the control group). Gross total resection was achieved in 26 patients, near total resection (≥90% but <100%) in 21, and subtotal resection in 11.
The baseline characteristics did not differ between treatment groups (Table
1).
Table 1
Patient characteristics
General data | Age (years) | 58.89 (±13.5) | 54.77 (±13.9) |
Sex (male/female) | 12/15 | 17/14 |
BMI | 25.73 (±6.18)a
| 25.42 (±4.12)b
|
Previous medical conditions | Arterial hypertension | 6 | 10 |
Coronary artery disease | 2 | 3 |
Hypothyroidism | 6 | 3 |
Atrial fibrillation | 1 | 0 |
Hypercholesterolemia | 0 | 4 |
Previous stroke | 0 | 0 |
Smokers | 3 | 5 |
Ex-smokers | 0 | 2 |
Regular medications | Aspirin | 2 | 3 |
Beta blockers | 4 | 2 |
Calcium channel blockers | 3 | 1 |
ACE inhibitors | 5 | 6 |
Anticoagulants | 1 | 0 |
Anticonvulsants | 10 | 14 |
Diuretics | 4 | 3 |
Statins | 3 | 2 |
Levothyroxine | 6 | 3 |
Antidepressants | 3 | 4 |
Other drugs | 1 | 5 |
Clinical data | Patients undergoing first resection | 10 | 15 |
Previous radiotherapy | 8 | 9 |
Previous chemotherapy | 10 | 10 |
Glioma patients previously treated with temozolomide | 6 | 4 |
Glioma patients previously treated with CCNU | 0 | 1 |
Preoperative Karnofsky (%) | 90 (80–100) | 100 (80–100) |
Tumor location | Frontal | 15 | 15 |
Temporal | 6 | 9 |
Parietal | 2 | 3 |
Basal ganglia | 1 | 2 |
Other locations | 3 | 2 |
Left hemisphere | 10 | 11 |
Right hemisphere | 12 | 14 |
Bilateral tumors | 5 | 6 |
Surgical data | ASA PS 1 | 1 | 3 |
ASA PS 2 | 17 | 23 |
ASA PS 3 | 6 | 3 |
Surgery duration (h) | 2.71 (±0.87) | 2.62 (±0.9) |
Use of intraoperative neuromonitoring (MEP/SEP) | 20 | 19 |
Gross total resection | 13 | 13 |
Near total resection | 9 | 12 |
Subtotal resection | 5 | 6 |
Intraoperative blood loss (ml) | 300 (200–300)c
| 300 (200–600)d
|
Hypoxemia (SaO2 ≤ 92%) | 1 e
| 0 f
|
Hypotension (MAP ≤65 mmHg) | 1 | 4 |
Use of intraoperative corticosteroids | 0 | 0 |
Intraoperative vessel damage | 0 | 0 |
Histopathological findings in patients with glioma | LGG (WHO I and II) | 3 | 4 |
HGG (WHO III and IV) | 13 | 15 |
Glioblastoma | 6 | 6 |
Gliosarcoma | 0 | 1 |
Diffuse astrocytoma | 2 | 3 |
Anaplastic astrocytoma | 4 | 5 |
Oligodendroglioma | 0 | 1 |
Anaplastic oligodendroglioma | 2 | 3 |
Anaplastic oligoastrocytoma | 1 | 0 |
Ganglioglioma | 1 | 0 |
MGMT methylation | 5 | 7 |
1p/19q codeletion | 4 | 4 |
IDH1 mutation | 7 | 10 |
Histopathological findings in patients with metastasis | Adenocarcinoma | 6 | 4 |
Undifferentiated carcinoma | 0 | 2 |
Melanoma | 3 | 1 |
Squamous cell carcinoma | 1 | 1 |
Other | 1 | 4 |
Ischemic preconditioning and neurological deficits
New neurological deficits occurred in 4 of 27 patients in the rIPC group: anomic aphasia in 1, severe motor deficit (muscle strength (MS): 0–2/5) in 1, mild to moderate motor deficit (MS: 3–4/5) in 2 cases, and dysphagia in 1 case. The deficits were permanent in 2 of these patients at 3 months follow-up (anomic aphasia in 1, severe motor deficit in another). One patient presented with recovery of neurological function, and 1 patient died within 1 month after surgery.
In the control group, new neurological deficits were found in 5 of 31 patients: non-fluent aphasia in 1 case, dysarthria in 1 case, sensitive deficit in 2 cases, and mild to moderate motor deficit in 3 cases. Of these 5 patients, one had permanent deficits at 3 months follow-up (anomic aphasia and mild to moderate motor deficit). Three patients have shown improvement in neurological function, and one patient was lost to follow-up.
There was no significant difference between the two groups with respect to incidence of new neurological deficits (Fisher's exact test; p = 1).
Three of 27 patients in the rIPC group experienced postoperative deterioration of neurological symptoms: aphasia in 2 cases, severe motor deficit in 2 cases, and mild to moderate motor deficit in 1 case. At 3 months follow-up, only one of these patients had a permanent deficit (mild to moderate motor deficit).
In the control group, three patients had a postoperative worsening of neurological function (severe motor deficit). One of these patients presented a partial improvement of motor function (mild to moderate deficit) at 3 months follow-up. The other two patients were lost to follow-up.