Carotid Artery Bypass Surgery of In-Body Tissue Architecture-Induced Small-Diameter Biotube in a Goat Model: A Pilot Study.

Biotubes are autologous tubular tissues developed within a patient's body through in-body tissue architecture, and they demonstrate high potential for early clinical application as a vascular replacement. In this pilot study, we used large animals to perform implantation experiments in preparation for preclinical testing of Biotube. The biological response after Biotube implantation was histologically evaluated. The designed Biotubes (length: 50 cm, internal diameter: 4 mm, and wall thickness: 0.85 mm) were obtained by embedding molds on the backs of six goats for a predetermined period (1-5 months). The same goats underwent bypass surgery on the carotid arteries using Biotubes (average length: 12 cm). After implantation, echocardiography was used to periodically monitor patency and blood flow velocity. The maximum observation period was 6 months, and tissue analysis was conducted after graft removal, including the anastomosis. All molds generated Biotubes that exceeded the tensile strength of normal goat carotid arteries, and eight randomly selected Biotubes were implanted. Thrombotic occlusion occurred immediately postoperatively (1 tube) if anticoagulation was insufficient, and two tubes, with insufficient Biotube strength (<5 N), were ruptured within a week. Five tubes maintained patency for >2 months without aneurysm formation. The spots far from the anastomosis became stenosed within 3 months (3 tubes) when Biotubes had a wide intensity distribution, but the shape of the remaining two tubes remained unchanged for 6 months. The entire length of the bypass region was walled with an αSMA-positive cell layer, and an endothelial cell layer covered most of the lumen at 2 months. Complete endothelial laying of the luminal surface was obtained at 3 months after implantation, and a vascular wall structure similar to that of native blood vessels was formed, which was maintained even at 6 months. The stenosis was indicated to be caused by fibrin adhesion on the luminal surface, migration of repair macrophages, and granulation formation due to the overproliferation of αSMA-positive fibroblasts. We revealed the importance of Biotubes that are homogeneous, demonstrate a tensile strength > 5 N, and are implanted under appropriate antithrombotic conditions to achieve long-term patency of Biotube. Further, we clarified the Biotube regeneration process and the mechanism of stenosis. Finally, we obtained the necessary conditions for a confirmatory implant study planned shortly.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Low-flow perfusion technique for shaggy aortic arch.

BACKGROUND: The most common complication of thoracic aortic disease with shaggy aorta is cerebral infarction. We have performed "low-flow perfusion" as a method of extracorporeal circulation to prevent cerebral embolism in patients with strong atherosclerotic lesions in the aortic arch. METHODS: "Low-flow perfusion" is a method in which cardiopulmonary bypass is started by partial blood removal, approaching deep hypothermia while maintaining self-cardiac output. We compared the outcomes of 12 patients who underwent the "low-flow perfusion" method (Group L) with those of 12 who underwent normal extracorporeal circulation (Group N) during aortic arch surgery since 2019. RESULTS: Group L consisted of 8 males with an average age of 73 years old, and Group N consisted of 6 males with an average age of 73 years old. The average time from the start of cooling to ventricular fibrillation was 9.5 min in Group L and 3.6 min in Group N (p < 0.01). The eardrum temperature when ventricular fibrillation was reached was 28.2 °C in Group L and 32.5 °C in Group N (p = 0.01). A blood flow analysis also revealed low wall shear stress on the lesser curvature of the aortic arch. CONCLUSION: With this method, the intracranial temperature was sufficiently low at the time of ventricular fibrillation, and there was no need to increase the total pump flow. The low-flow perfusion method can prevent cerebral embolism by preventing atheroma destruction by the blood flow jet while maintaining the self-cardiac output during the cooling process.

A case of sigmoid colon perforation due to segmental absence of intestinal musculature (SAIM) accompanied by vascular Ehlers-Danlos syndrome: a case report.

BACKGROUND: Segmental absence of intestinal musculature (SAIM) is a partial defect of the intrinsic muscular layer of the intestinal tract. In this report, we describe a case of perforation of the sigmoid colon due to SAIM accompanied by vascular Ehlers-Danlos syndrome (vEDS), which was successfully treated by surgical therapy. CASE PRESENTATION: A male in his 30 s was being followed up for vEDS diagnosed by genetic testing. He had undergone two major vascular surgeries, abdominal aortic artery revascularization and thoracic endovascular aortic repair for a residual dissection and enlarging abdominal aortic aneurysm. On postoperative day 11, the patient developed perforation of the sigmoid colon for which intraperitoneal lavage and drainage, Hartmann surgery, and transverse colostomy were performed. Histological findings showed no disturbance of blood flow or diverticulum but did show a defect in the intrinsic muscular layer around the perforation site, leading to the pathological diagnosis of SAIM and associated perforation of the sigmoid colon. Postoperatively, the patient had no complications and was discharged on postoperative day 18. The patient is being followed as an outpatient and has experienced no relapse. CONCLUSIONS: Both SAIM and vEDS, which may be related diseases, are associated with the presence of tissue fragility and have a high potential to cause intestinal perforation Caution should be exercised during surveillance in patients with constipation and examinations that cause increased intestinal pressure.

Leiomyosarcoma Presenting as Rupture With a Type II Endoleak After Thoracic Endovascular Aortic Repair.

Endovascular stent-graft therapy is a commonly performed procedure for aortic lesions worldwide and complications unique to stent grafts, such as postoperative endoleaks, are well known. However, as this treatment modality becomes more popular, physicians should carefully monitor for other unexpected complications, which may not always be related to the graft. This study presents a case of leiomyosarcoma of the aorta that developed during follow-up for a type II endoleak (T2EL) after thoracic endovascular aortic repair. The presence of the T2EL hindered the diagnosis of the sarcoma at an early stage. These findings suggest that an apparent aneurysm that grows suddenly during follow-up after stent grafting should raise the index of suspicion for a neoplasm as well as an endoleak.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Uterine Cervical and Endometrial Carcinomas: Histopathological Analysis of Survival and Local Control. A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study.

OBJECTIVE: A retrospective comparative analysis of the outcomes of gamma knife radiosurgery (GKRS) for brain metastases from uterine cervical carcinoma (CC) and endometrial carcinoma (EC), investigated the efficacy and prognostic factors for survival and local tumor control. Histopathological analysis was also performed. METHODS: The authors retrospectively reviewed 61 patients with 260 tumors of CC and 73 patients with 302 tumors of EC who had undergone GKRS. RESULTS: The survival times after GKRS had no difference between CC and EC. Uncontrolled primary cancer was significant unfavorable factor. CC resulted in significantly higher neurological death and post-GKRS neurological deterioration. New lesions appeared intracranially after GKRS, with no significant difference between CC and EC. Local tumor control rates at 6, 12, and 24 months after GKRS were 90.0%, 86.6%, and 78.0% for CC and 92.2%, 87.9%, and 86.4% for EC. Primary cancer of CC, more than 7 cm3 volume, and prescription dose less than 20 Gy were significantly correlated in control failure. Local tumor control rates were significantly lower for squamous cell carcinoma in CC. No significant differences were found between histopathological subtypes of EC. CONCLUSIONS: This study established a relationship between the efficacy of GKRS for CC and EC brain metastases and the histopathological. Though, survival time after GKRS has no difference between CC and EC, CC was significantly higher neurogenic death and neurological deterioration after GKRS. Squamous cell carcinoma had a significantly lower rate of local tumor control among all CC, thereby resulting in CC having lower local tumor control than EC.

Primary central nervous system other iatrogenic immunodeficiency-associated lymphoproliferative disorders presenting as extraosseous plasmacytoma with a progressive clinical course: A case report and literature review.

Other iatrogenic immunosuppressive-associated lymphoproliferative disorders (OIIA-LPDs) rarely occur in the central nervous system (CNS). Additionally, they almost always present as lymphoma and withdrawal by cessation of immunosuppressive treatment. We report a case of primary CNS OIIA-LPD that presented as extraosseous plasmacytoma (EP) with a progressive clinical course in spite of immunosuppressive treatment cessation. A 78-year-old man with a history of rheumatoid arthritis (RA) presented with a month-long headache. Magnetic resonance imaging showed mass lesions in the left temporal lobe, left middle fossa, and intradural cervical spine. The left temporal lesion was resected and diagnosed as EP histologically, and OIIA-LPD presented as plasmacytoma integrally due to his history of immunosuppressive treatment using tacrolimus for RA. Despite immunosuppressive treatment cessation, OIIA-LPD lesions did not regress but, on the contrary, showed a progressive clinical course. Considering his advanced age and renal dysfunction, postoperative treatment with radiation and moderate chemotherapy using prednisolone were administrated. Subsequently, the disease state stabilized, and the patient had a Karnofsky performance status score of 90 for 6 months; however, the tumor recurred with meningeal dissemination, and he died 8 months after treatment. Types of OIIA-LPD onset as EP and its progressive clinical course resistant to cessation of immunosuppressive treatment are rare. Moreover, this OIIA-LPD disease state worsened despite its radiosensitivity. We believe the progressive clinical course of this OIIA-LPD case with its high cell proliferation is similar to Epstein-Barr virus negative plasmablastic lymphoma, which could lead to a poor outcome.

Stereotactic intensity-modulated radiotherapy for skull base meningioma using the HybridArc with Novalis STx system.

Background: Skull base meningiomas are often difficult to remove completely with preserved nerve function and may require radiation therapy. However, the Gamma Knife is unsuitable for large tumor volume or the optic nerve, which is difficult to identify on imaging. We report the results of stereotactic radiotherapy with HybridArc using Novalis STx for skull base meningiomas. Methods: We retrospectively examined 28 patients with skull base meningioma who underwent stereotactic radiotherapy (54 Gy/30 fractions) with HybridArc. Results: The 28 patients, nine males and 19 females, were aged 31-83 years (mean 58.4 years), and the tumor volume was 2.6-97.1 mL (mean 29.7 mL). HybridArc irradiation was performed with D95 54 Gy/30 fractions for all patients with a median follow-up period of 36.0 months (range: 12-78 months). Tumor control rates at 1, 2, and 5 years after radiotherapy were 92.6%, 89.1%, and 82.8%, respectively. Only one non-atypical meningioma remained uncontrolled; thus, the tumor control rate for non-atypical meningioma at 1, 2, and 5 years was 94.1%. Tumor control rates for atypical meningioma at 1, 2, and 5 years were 85.7%, 71.4%, and 53.6%, respectively, significantly worse than for non-atypical meningiomas (P = 0.0395). Radiation injury was observed in two cases (7.1%). Visual field defects were observed in 16 patients, and diplopia in 6. Visual field and diplopia improvements were achieved in 5 and 2 patients, respectively (with overlap). Conclusion: Stereotactic radiotherapy (54 Gy/30 fractions) with HybridArc using Novalis STx is a safe and effective approach for relatively large skull base meningiomas.

Gamma Knife radiosurgery for metastatic brain tumors from ovarian cancer: histopathological analysis of survival and local control. A Japanese multi-institutional cooperative and retrospective cohort study.

OBJECTIVE: Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed. METHODS: The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan. RESULTS: After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005). CONCLUSIONS: This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

Stereotactic radiosurgery results for brain metastasis patients with renal cancer: A validity study of Renal Graded Prognostic Assessment and proposal of a new grading index (JLGK2101 Study).

BACKGROUND AND PURPOSE: The Renal Graded Prognostic Assessment (GPA) is relatively new and has not been sufficiently validated using a different dataset. We thus developed a new grading index, the Renal Brain Metastasis Score (Renal-BMS). MATERIALS AND METHODS: Using our dataset including 262 renal cancer patients with brain metastases (BMs) undergoing stereotactic radiosurgery (SRS) (test series), we validity tested the Renal-GPA. Next, we applied clinical factor-survival analysis to the test series and thereby developed the Renal-BMS. This system was then validated using another series of 352 patients independently undergoing SRS at nine gamma knife facilities in Japan (verification series). RESULTS: Using the test series, with the Renal-GPA, 95% confidence intervals (CIs) of the post-SRS median survival times (MSTs) overlapped between pairs of neighboring subgroups. Among various pre-SRS clinical factors of the test series, six were highly associated with overall survival. Therefore, we assigned scores for six factors, i.e., "KPS ≥ 80%/<80% (0/3)", "tumor numbers 1-4/≥5 (score; 0/2)", "controlled primary cancer/not (0/2)", "existing extra-cerebral metastases/not (0/3)", "blood hemoglobin ≥ 11.0/<11.0 g/dl (0/1)" and "interval from primary cancer to SRS ≥ 5/<5 years (0/1)". Patients were categorized into three subgroups according to the sum of scores, i.e., 0-4, 5-8 and 9-12. In the test and verification series, post-SRS MSTs differed significantly (p < 0.0001) with no overlaps of 95% CIs among the three subgroups. CONCLUSIONS: The Renal BMS has the potential to be very useful to physicians selecting among aggressive treatment modalities for renal cancer patients with BMs.

Effects of two different radiotherapies for craniopharyngiomas using stereotactic radiosurgery/ stereotactic radiotherapy or fractionated stereotactic radiotherapy.

Background: Numerous studies have reported about good tumor control with both stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for residual and recurrent craniopharyngiomas, but no studies have reported on the appropriate use of different types of radiation modalities. This study aimed to report the outcomes of SRS/stereotactic radiotherapy (SRT) or FSRT and compare tumor control in a single center. Methods: From 2014 when TrueBeamTM STx with Novalis was introduced in our hospital to 2021, 21 patients underwent SRS/SRT or FSRT with gamma knife surgery (GKS) and Novalis. We have selected the radiation modalities considering mainly the distance of the optic nerve and chiasm. Imaging and clinical follow-up data were sent and reviewed. Results: The mean age was 52 years and there were 11 men. Of the 21 total patients, three experienced SRS (GKS, 50% isodose 12-15 Gy), five underwent SRT (GKS or Novalis, 19.5-24 Gy 3 fractions), and 13 patients underwent FSRT (Novalis, 54 Gy 30 fractions). The median follow-up was 32.6 (range 17-44) months after SRS/SRT and 34.0 (range 4-61) months after FSRT. In the SRS/SRT group, the mean tumor volume decreased from 1.103 to 0.131 cm3 (P < 0.01), and in the FSRT group, from 3.015 to 1.012 cm3 (P < 0.01). No radiation-induced optic neuropathy and other acute toxicity occurred. Conclusion: Craniopharyngioma can be expected to have very good tumor control by selecting SRS/SRT or FSRT depending on the distance between the optic nerve and the tumor.

Extensive Aortic Stent Graft Coverage for Thoracoabdominal Aortic Aneurysm is Associated With Hemorrhagic Complications Induced by Disseminated Intravascular Coagulation.

BACKGROUND: Hybrid endovascular repair for thoracoabdominal aortic aneurysm (TAAA) is a less invasive alternative treatment than conventional open repair. However, disseminated intravascular coagulation (DIC) and hemorrhagic complications can occur postoperatively. We investigated risk factors for hemorrhagic complications after hybrid endovascular TAAA repair. METHODS: Sixty-one patients who underwent elective hybrid endovascular TAAA repair between 2007 and 2020 were included. Laboratory data before and after placing stent graft were collected, and DIC was diagnosed using a scoring system established by the Japanese Association for Acute Medicine. The length of the stent graft used to cover the aorta was defined as the aortic coverage length, which was measured using the first postoperative computed tomography image. Predictors of unexpected hemorrhagic complications were evaluated. RESULTS: Postoperative thrombocytopenia was observed in 57 (93%) patients, and their platelet count decreased significantly after stent graft placement (14.3 [9.5-18.0] vs. 8.2 [5.4-10.9] × 104/µL, P < 0.001). Fifteen (25%) and 45 patients (74%) were diagnosed with DIC before and after stent graft placement, respectively. Hemorrhagic complications were observed in 21 patients (34%). Multivariate logistic regression analysis revealed that aortic coverage length was an independent risk factor for hemorrhagic complications (odds ratio 1.441/50 mm increase; 95% confidence interval, 1.041-1.994, P = 0.027). The cutoff value for aortic coverage length obtained from the receiver operating characteristic curve (area under the curve = 0.72) was 304.4 mm (sensitivity 0.76, specificity 0.70). CONCLUSION: Aortic coverage length is a risk factor for hemorrhagic complications. Patients undergoing extensive aortic coverage greater than 304 mm should be closely monitored.

Proposal criteria of paradoxical low-flow low-gradient aortic stenosis for predicting prognosis in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) is associated with poor prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). This study aimed to verify the conventional criteria of PLF-LG AS (left ventricular ejection fraction [LVEF] > 50%, mean aortic valve pressure gradient [AVPG] < 40 mm Hg and stroke volume index [SVI] < 35 ml/m2 by measuring Doppler method) compatible for predicting prognosis in patients undergoing TAVI. MATERIALS AND METHODS: A total of 128 consecutive patients who underwent TAVI for AS with LVEF > 50% were enrolled. The primary endpoint was the hospital readmission due to heart failure (HRHF) and the secondary endpoint was all-cause mortality after hospital discharge. The patients were classified by both the conventional criteria of PLF-LG AS and the proposal criteria of PLF-LG AS if mean aortic valve pressure gradient (AVPG) < 40 mmHg and SVI by measuring Simpson's method < cut off value based on the ROC curve for predicting HRHF. RESULTS: According to the conventional criteria, only 6 patients were diagnosed with PLF-LG AS. However, according to the proposal criteria, 16 patients were diagnosed with PLF-LG AS. Fourteen patients developed HRHF during the follow-up period after TAVI. Based on the ROC curves, SVI by measuring Simpson's method (cut off value = 25 ml/m2) had higher sensitivity and specificity for predicting HRHF (AUC = 0.74, p = 0.0013) than SVI by measuring Doppler method (AUC = 0.63, p = 0.045). The multivariate analysis revealed that PLF-LG AS defined by the proposal criteria (HR: 5.25; 95% CI: 1.60-17.16; p = 0.0073) but not by the conventional criteria was independently associated with HRHF. PLF-LG AS defined by the conventional criteria and the proposal criteria were not associated with all-cause mortality in the univariate analysis. CONCLUSIONS: Our results demonstrated that new criteria of PLF-LG AS defined as SVI < 25 ml/m2 measured by Simpson's method could predict HRHF in patients with severe AS who underwent TAVI.

Volume-Staged Radiosurgery for Large Arteriovenous Malformation: Retrospective Analysis of 19 Cases.

Introduction The effectiveness of Gamma Knife surgery (GKS) for small arteriovenous malformations (AVMs) is well known. However, for large AVMs, the prescribed dose should be decreased to reduce the risk of radiation damage, but it leads to a decrease in nidus obliteration rates. Therefore, it is very difficult to achieve complete obliteration of large AVMs in a single treatment, and methods using multiple irradiation such as volume-staged stereotactic radiosurgery (VS-SRS) have been suggested. We retrospectively reviewed our results of VS-SRS for large AVMs to assess the efficacy of VS-SRS. Methods Nineteen patients with AVMs of ≥10 ml and who consented to VS-SRS were treated by this surgical strategy and retrospectively analyzed. We excluded AVMs that were too large such as those >40 cc to avoid severe radiation damage. The components were divided mainly in the vertical direction, and each component was irradiated with a marginal dose of 18 Gy. Each irradiation was performed at intervals of 3-6 months, and the components with main feeders were irradiated first, and the components that included the main drainer were irradiated last. We tried to keep V18 to <10 ml if possible. The follow-up after GKS was performed by MRI every 6 months, and cerebral angiography was performed to confirm complete nidus obliteration, but if the patient refused, it was judged on the basis of MRI findings. Results Nineteen patients with a mean age of 40.2 years underwent VS-SRS. Each compartment was irradiated at 3--16 month (median, 3 months) intervals. The mean initial AVM volume was 19 ± 5.6 ml. Fourteen patients received two-stage radiosurgery and five received three-stage radiosurgery. The median target volume was 9.1 ml at stage 1, 9.0 ml at stage 2, and 10.1 ml at stage 3. The median margin dose was 18 Gy at each stage. The mean follow-up after the last stage of radiosurgery was 3.9 (1-11.4) years. Complete obliteration was confirmed by angiography in six patients, and by magnetic resonance angiography in one patient. The cumulative obliteration rates were 30.7% and 58.2% at 3 and 5 years following VS-SRS, respectively. The cumulative hemorrhage rates were 7.1% and 22.1% at 3 and 5 years, respectively. MRI showed T2-weighted prolongation in 15 patients (78.9%). Of these 15 patients, four were symptomatic (epilepsy in all) and two underwent surgical removal of symptomatic expanding hematomas. Conclusions In our experience, VS-SRS offers a viable treatment strategy in patients with large AVMs. Further optimization of the dose and volume at each stage is required.

Detection of fibrotic remodeling of epicardial adipose tissue in patients with atrial fibrillation: Imaging approach based on histological observation.

BACKGROUND: Fibrotic remodeling of epicardial adipose tissue (EAT) is crucial for proinflammatory atrial myocardial fibrosis, which leads to atrial fibrillation (AF). OBJECTIVES: We tested the hypothesis that the ratio of central to marginal adipocyte diameter in EAT represents its fibrotic remodeling. Based on a similar concept, we also tested whether the percent (%) change in EAT fat attenuation determined using computed tomographic (CT) images can detect this remodeling. METHODS: Left atrial appendages were obtained from 76 consecutive AF patients during cardiovascular surgery. EAT in the central area (central EAT: C-EAT) and that adjacent to the atrial myocardium (Marginal EAT: M-EAT) were evaluated histologically. CT images for all of the 76 patients were also analyzed. RESULTS: The adipocyte diameter was smaller, fibrotic remodeling of EAT (EAT fibrosis) was more severe, and infiltration of macrophages and myofibroblasts was more extensive in M-EAT than in C-EAT. EAT fibrosis was positively correlated with adipocyte diameter in C-EAT and negatively correlated in M-EAT, resulting in a positive correlation between EAT fibrosis and the ratio of central to marginal adipocyte diameter (C/M diameter ratio; r = 0.73, P < .01). The C/M diameter ratio was greater in patients with persistent AF than in those with paroxysmal AF. CT images demonstrated that the %change in EAT fat attenuation was positively correlated with EAT fibrosis. CONCLUSION: Our results suggest that the central-to-marginal adipocyte diameter ratio is tightly associated with fibrotic remodeling of EAT. In addition, the %change in EAT fat attenuation determined using CT imaging can detect remodeling noninvasively.

Aortic valve neocuspidization with in-body tissue-engineered autologous membranes: preliminary results in a long-term goat model.

OBJECTIVES: Aortic valve neocuspidization has shown satisfactory clinical outcomes; however, autologous pericardium durability is a concern for young patients. This study applied an autologous collagenous membrane (Biosheet®), produced by in-body tissue architecture, to aortic valve neocuspidization and investigated its long-term outcome in a goat model. METHODS: Moulds were embedded subcutaneously in 6 goats. After 2 months, Biosheets formed in the moulds. We performed aortic valve neocuspidization using a portion of the sheets with a thickness of 0.20-0.35 mm, measured by optical coherence tomography. Animals were subjected to echocardiography and histological evaluation at 6 months (n = 3) and 12 months (n = 3). As a control, the glutaraldehyde-treated autologous pericardium was used in 4 goats that were similarly evaluated at 12 months. RESULTS: All animals survived the scheduled period. At 6 months, Biosheets maintained valve function and showed a regeneration response: fusion to the annulus, cell infiltration to the leaflets and appearance of elastic fibres at the ventricular side. After 12 months, the regenerative structure had changed little without regression, and there was negligible calcification in the 1/9 leaflets. However, all cases had one leaflet tear, resulting in moderate-to-severe aortic regurgitation. In the pericardium group, three-fourths of the animals experienced moderate-to-severe aortic regurgitation with a high rate of calcification (9/12 leaflets). CONCLUSIONS: Biosheets may have regeneration potential and anti-calcification properties in contrast to autologous pericardium. However, in order to obtain reliable outcome, further improvements are required to strictly control and optimize its thickness, density and homogeneity.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer.

Introduction The outcomes after gamma knife radiosurgery (GKRS) were retrospectively analysed in patients with brain metastases from anaplastic lymphoma kinase (ALK) rearrangement-positive and epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) to evaluate the efficacy, safety and difference for overall survival and local tumor control. Methods The medical records were retrospectively reviewed of 607 patients (25 ALK-positive, 171 EGFR-positive, and 411 wild type) with 2959 tumors who had undergone GKRS. Results The median overall survival time after initial GKRS was 14 months. Driver gene mutation-positive patients had significantly longer overall survival than wild type patients (p < 0.0001), and ALK-positive patients survived significantly longer than EGFR-positive patients (p = 0.04). Multivariate analysis showed the unfavorable factors significantly affecting overall survival outcomes were older age, lower Karnofsky Performance Status score, multiple intracranial metastases, uncontrolled primary cancer, uncontrolled extracranial metastases, no administration of immune checkpoint inhibitors, and driver gene mutation-negative cases. Seventy-three patients died of uncontrolled brain metastases at a median of 12 months. Driver gene mutations had no influence (p = 0.33), and ALK-positive and EGFR-positive patients showed no significant difference in neurological survival (p = 0.83). A total of 174 patients demonstrated distant brain control failure at a median of 15 months. ALK-positive type was significant compared with EGFR-positive type (p = 0.047), but driver gene mutation-positive and -negative types showed no significant difference in the development of new brain metastases (p = 0.2). The median tumor volume was 1.06 cm3 in the driver gene mutation-positive type and 1.85 cm3 in wild type. The median marginal dose was 20 Gy in both types. The 6-, 12-, and 24-month local tumor control rates were 97.3%, 96.1%, and 95.9%, respectively. Driver gene mutations had a significantly positive impact on local tumor control (p = 0.001), and ALK-positive and EGFR-positive types showed no significant difference (p = 0.95). A total of 193 tumors had radiation injury at a median of 12 months after GKRS. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 8.1%, and 8.7%, respectively. Driver gene mutations significantly induced radiation damage (p = 0.021), and the ALK-positive type was affected more than the EGFR-positive type (p = 0.02). Conclusions ALK rearrangement-positive NSCLC patients tended to have significantly longer survival, but had higher incidence of new intracranial metastases due to long-term survival after GKRS, compared with EGFR mutation-negative and driver gene mutation-negative NSCLC patients. GKRS induced significantly satisfactory local tumor control in driver gene mutation-positive tumors but GKRS-related complication frequency was higher, especially in ALK-positive NSCLC patients. Therefore, more careful imaging follow-up is necessary after GKRS for patients with driver gene mutation-positive NSCLC.

True Aneurysm of the Left Main Trunk in a Marfan Syndrome Patient at Remote Period after Bentall Operation and Total Arch Replacement: A Case Report.

In 2002, a 37-year-old male with Marfan syndrome underwent the Bentall operation, total arch replacement, and aortobifemoral bypass for DeBakey type IIIb chronic aortic dissection, annuloaortic ectasia, and aortic regurgitation. In 2007, mild mitral regurgitation (MR) caused by mitral valve prolapse was identified. In April 2017, echocardiography revealed the worsening of MR and moderate tricuspid regurgitation (TR). Moreover, coronary angiography (CAG) revealed a coronary artery aneurysm in the left main trunk (LMT). In August 2017, the patient underwent mitral valve replacement (MVR), tricuspid annuloplasty (TAP), and coronary artery reconstruction. We reconstructed the LMT aneurysm using an artificial graft. True aneurysm of the coronary artery complicated with Marfan syndrome is a rare complication that has seldom been reported. This case highlights that it is essential to carefully follow-up patients with Marfan syndrome after the Bentall operation.

Femoral artery anatomy is a risk factor for limb ischemia in minimally invasive cardiac surgery.

OBJECTIVE: In minimally invasive cardiac surgery (MICS), femoral artery cannulation during cardiopulmonary bypass (CPB) can cause limb ischemia. This study evaluated the association between femoral artery anatomy and the risk of limb ischemia in MICS. METHODS: Eighty-one patients who underwent MICS with CPB using single femoral artery cannulation between 2010 and 2018 were included. The patients were stratified by their femoral artery diameter and anatomy of ectopic side branch, i.e., medial or lateral femoral circumflex arteries: Type A, deep femoral artery (DFA) ≥ superficial femoral artery (SFA); type B, DFA < SFA with an ectopic side branch of the common femoral artery (CFA); type C, DFA < SFA with an ectopic side branch at the CFA bifurcation; and type D, DFA < SFA without an ectopic side branch. The ratio of the postoperative creatine kinase concentration and the cross-sectional area of the femoral muscles (CK/MA) was used as a surrogate marker of limb ischemia. Predictors of high CK/MA were evaluated. RESULTS: No critical limb ischemia was observed in this study. The median postoperative creatine kinase and CK/MA were 1954 (1305-2872) IU/l and 15.2 (9.2-19.8) IU/l/cm2. Multivariable logistic regression found that anatomical type D (odds ratio 4.19, 95% confidence interval: (1.26-14.0); p = 0.020) and prolonged CPB time (OR 1.01, 95% CI (1.00-1.02); p = 0.045) were independent risk factors of high CK/MA. CONCLUSION: Anatomical type D and prolonged CPB time were associated with risk of limb ischemia in MICS.

Acute Management of Gamma Knife Radiosurgery for Asymptomatic Obstructive Hydrocephalus Associated with Posterior Fossa Metastases.

OBJECTIVE: We retrospectively assessed the effectiveness and safety of Gamma Knife radiosurgery (GKRS) for asymptomatic obstructive hydrocephalus associated with posterior fossa metastases, which was known empirically but not well discussed. METHODS: We reviewed the medical records of 27 patients who underwent GKRS for asymptomatic obstructive hydrocephalus related to posterior fossa metastases. RESULTS: Cumulative control rates of hydrocephalus were 11.1%, 51.9%, 70.4%, and 74.6% at 1, 2, 3, and 6 months after GKRS. Primary gastrointestinal tract cancer (P = 0.001) was significantly correlated with unfavorable management. Evans ratio at GKRS (median 0.31) improved significantly compared with that at 1-3 months after GKRS (median 0.26) (P < 0.0001) and maintained at 6 to 12 months. Cumulative local tumor control rates were 91.7%, 70.8%, and 64.4% at 3, 6, and 12 months after GKRS. Primary gastrointestinal tract cancer (P = 0.018) and no conventional systemic agents (P = 0.027) were significantly correlated with unfavorable control. Cumulative incidence rates of adverse radiation effects were 0.0%, 16.7%, and 24.2% at 6, 9, and 12 months after GKRS. Primary gastrointestinal tract cancer (P < 0.0001) and single and 2- or 3-fraction GKRS (P < 0.0001) were significantly correlated with unfavorable outcomes. All but 1 patient avoided surgical procedure for hydrocephalus after GKRS. CONCLUSIONS: The present findings suggest that GKRS is an effective and safe treatment for asymptomatic obstructive hydrocephalus caused by posterior fossa metastases, and all but 1 could avoid invasive surgical procedures for hydrocephalus. Posterior fossa metastases from gastrointestinal tract cancer resulted in unsatisfactory outcomes for control of hydrocephalus, tumor progression, and adverse radiation effects.