The Role of Radiotherapy for Meningeal Melanocytomas - A 20 Year Update.

BACKGROUND/AIM: Meningeal melanocytomas are rare tumors of the central nervous system and optimal treatment needs further clarification. This study compared subtotal resection (STR), STR plus radiation therapy (RT), gross total resection (GTR), and GTR+RT to better define the role of postoperative RT. PATIENTS AND METHODS: All cases reported in the literature were reviewed. Patients (n=184) with complete data were analyzed for local control (LC) and overall survival (OS). RESULTS: On univariate analysis, GTR (vs. STR) was associated with improved LC (p=0.016). When comparing the treatment regimens, best and worst results were found after GTR+RT and STR alone, respectively (p<0.001). On univariate analysis, GTR resulted in better OS than STR (p=0.041). Moreover, the treatment regimen had a significant impact on OS (p=0.049). On multivariate analyses of LC and OS, extent of resection and treatment regimen were found to be significant factors. After STR, RT significantly improved LC but not OS. After GTR, RT did not significantly improve LC or OS. CONCLUSION: GTR was significantly superior to STR regarding LC and OS. STR+RT resulted in significantly better LC when compared to STR alone.

Whole-brain Radiotherapy With or Without a Simultaneous Integrated Boost for Treatment of Brain Metastases.

BACKGROUND/AIM: Many patients with brain metastases receive whole-brain radiotherapy (WBRT), despite the increasing use of stereotactic radiotherapy alone. A more recent approach includes WBRT combined with simultaneous integrated boost (WBRT+SIB). This study compared WBRT alone and WBRT+SIB for unresected brain metastases. PATIENTS AND METHODS: One-hundred-and-three patients receiving WBRT+SIB were compared to 275 patients receiving WBRT alone for intracerebral control (IC) and overall survival (OS). RESULTS: Both treatment groups (WBRT alone and WBRT+SIB) were balanced with respect to patient characteristics. On multivariate analyses, WBRT+SIB (p=0.041), Karnofsky performance score (KPS) >70 (p<0.001), and 1-3 brain metastases (p=0.016) were significantly associated with IC. KPS >70 (p<0.001), favorable tumor type (p=0.011), 1-3 brain metastases (p=0.011), and absence of extracranial metastases (p<0.001) were significantly associated with OS. CONCLUSION: WBRT+SIB is associated with improved IC but similar OS when directly compared to WBRT for brain metastases. Selected patients with a high risk of intracerebral recurrence may benefit from SIB.

Stereotactic Radiotherapy or Whole-Brain Irradiation Plus Simultaneous Integrated Boost After Resection of Brain Metastases.

BACKGROUND/AIM: Most patients with resected brain metastases receive post-operative radiotherapy. This study investigated outcomes of fractionated stereotactic radiotherapy (FSRT) alone or whole-brain irradiation plus simultaneous integrated boost (WBI+SIB) in the post-operative setting. PATIENTS AND METHODS: Forty-four patients receiving FSRT alone (n=32) or WBI+SIB (n=12) after resection of 1-3 brain metastases from 2014-2022 were analyzed. Twelve factors were evaluated for local control (LC), distant brain control (DBC), and overall survival (OS). RESULTS: On univariate and multivariate analyses, single brain metastasis was associated with improved LC and DBC. Longer interval between tumor diagnosis and radiotherapy, single brain metastasis, and Karnofsky performance score >80 were associated with improved OS. WBI+SIB showed a trend towards better DBC. CONCLUSION: Several independent predictors of outcomes after FSRT or WBI+SIB following resection of brain metastases were identified. Given similar survival in the post-operative setting between FSRT and WBI+SIB, potential toxicity remains a significant factor in treatment recommendations.

Radiotherapy with or without Decompressive Surgery for Metastatic Spinal Cord Compression: A Retrospective Matched-Pair Study Including Data from Prospectively Evaluated Patients.

In 2005, a randomized trial showed that addition of surgery to radiotherapy improved outcomes in patients with metastatic spinal cord compression (MSCC). Since then, only a few studies compared radiotherapy plus surgery to radiotherapy alone. We performed a retrospective matched-pair study including data from prospective cohorts treated after 2005. Seventy-nine patients receiving radiotherapy alone were matched to 79 patients assigned to surgery plus radiotherapy (propensity score method) for age, gender, performance score, tumor type, affected vertebrae, other bone or visceral metastases, interval tumor diagnosis to MSCC, time developing motor deficits, and ambulatory status. Improvement of motor function by ≥1 Frankel grade occurred more often after surgery plus radiotherapy (39.2% vs. 21.5%, p = 0.015). No significant differences were found for post-treatment ambulatory rates (59.5% vs. 67.1%, p = 0.32), local progression-free survival (p = 0.47), overall survival (p = 0.51), and freedom from in-field recurrence of MSCC (90.1% vs. 76.2% at 12 months, p = 0.58). Ten patients (12.7%) died within 30 days following radiotherapy alone and 12 patients (15.2%) died within 30 days following surgery (p = 0.65); 36.7% of surgically treated patients did not complete radiotherapy as planned. Surgery led to significant early improvement of motor function and non-significantly better long-term control. Patients scheduled for surgery must be carefully selected considering potential benefits and risk of perioperative complications.

Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage: Angiographic Pattern and Its Impact on the Clinical Course.

OBJECTIVE: To analyze angiographic characteristics of cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH) and their potential impact on secondary infarction and functional outcome. METHODS: Demographic, clinical, and imaging data of sSAH patients with angiographic CVS admitted over a 6-year period were retrospectively analyzed. RESULTS: A total of 85 patients were included in the final analysis. A total of 311 arterial territories in 85 angiographies demonstrated angiographic CVS. The anterior cerebral artery (ACA) was the most common site of angiographic CVS (42.1%), followed by the middle cerebral artery (MCA) (26.7%). In 29 angiographies (34%) CVS was found in more than 3 vessels and a bilateral pattern was identified in 53 cases (62%). Older age (OR 3.24 [95% CI 1.30-8.07], P = 0.012) was identified as the only significant risk factor for CVS-related infarction (OR 22.67, P = 0.015). Unfavorable outcome was associated with older age (OR 3.24, P = 0.023) and poor World Federation of Neurosurgical Societies grade (OR 3.64, P = 0.015). Analyses of angiographic characteristics did not reveal any risk factors for unfavorable outcome. We identified distal CVS as a significant risk factor for CVS-related infarction (OR 2.89, P = 0.026). CONCLUSIONS: Angiographic CVS after sSAH shows a specific distribution pattern in favor of ACA and MCA and in most cases 2-3 affected vessels are affected, often bilaterally. Patients exhibiting distal CVS have a higher risk for CVS-related infarction and should be observed closely. Nonetheless, the majority of angiographic characteristics did not allow conclusions about functional outcome nor the occurrence of CVS-related infarction in sSAH patients.

Cerebral effects of resuscitation with either epinephrine or vasopressin in an animal model of hemorrhagic shock.

PURPOSE: The use of epinephrine (EN) or vasopressin (VP) in hemorrhagic shock is well established. Due to its specific neurovascular effects, VP might be superior in concern to brain tissue integrity. The aim of this study was to evaluate cerebral effects of either EN or VP resuscitation after hemorrhagic shock. METHODS: After shock induction fourteen pigs were randomly assigned to two treatment groups. After 60 min of shock, resuscitation with either EN or VP was performed. Hemodynamics, arterial blood gases as well as cerebral perfusion pressure (CPP) and brain tissue oxygenation (PtiO2) were recorded. Interstitial lactate, pyruvate, glycerol and glutamate were assessed by cerebral and subcutaneous microdialysis. Treatment-related effects were compared using one-way ANOVA with post hoc Bonferroni adjustment (p < 0.05) for repeated measures. RESULTS: Induction of hemorrhagic shock led to a significant (p < 0.05) decrease of mean arterial pressure (MAP), cardiac output (CO) and CPP. Administration of both VP and EN sufficiently restored MAP and CPP and maintained physiological PtiO2 levels. Brain tissue metabolism was not altered significantly during shock and subsequent treatment with VP or EN. Concerning the excess of glycerol and glutamate, we found a significant EN-related release in the subcutaneous tissue, while brain tissue values remained stable during EN treatment. VP treatment resulted in a non-significant increase of cerebral glycerol and glutamate. CONCLUSIONS: Both vasopressors were effective in restoring hemodynamics and CPP and in maintaining brain oxygenation. With regards to the cerebral metabolism, we cannot support beneficial effects of VP in this model of hemorrhagic shock.

The Impact of Intrahospital Transports on Brain Tissue Metabolism in Patients with Acute Brain Injury.

BACKGROUND: Patients with severe acute brain injury (ABI) often require intrahospital transports (IHTs) for repeated computed tomography (CT) scans. IHTs are associated with serious adverse events (AE) that might pose a risk for secondary brain injury. The goal of this study was to assess IHT-related alterations of cerebral metabolism in ABI patients. METHODS: We included mechanically ventilated patients with ABI who had continuous multimodality neuromonitoring during an 8-h period before and after routine IHT. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PtiO2) as well as cerebral and subcutaneous microdialysis parameters (lactate, pyruvate, glycerol, and glutamate) were recorded. Values were compared between an 8-h period before (pre-IHT) and after (post-IHT) the IHT. RESULTS: A total of 23 IHT for head CT scans in 18 patients were analyzed. Traumatic brain injury (n = 7) was the leading cause of ABI, followed by subarachnoid hemorrhage (n = 6) and intracerebral hemorrhage (n = 5). The analyzed microdialysis parameters in the brain tissue as in the subcutaneous tissue did not show significant changes between the pre-IHT and post-IHT period. In addition, we observed no significant increase in ICP or decrease in CPP and PtiO2 in the 8-h period after IHT. CONCLUSIONS: While the occurrence of AE during IHT is a known risk factor for ABI patients, our results demonstrate that IHTs do not alter the brain tissue chemistry in a significant manner. This fact may help assess the risk for routine IHT more accurately.

The Impact of Extubation Failure in Patients with Good-Grade Subarachnoid Hemorrhage.

OBJECTIVE: To analyze the clinical impact of extubation failure (EF) in patients with good-grade subarachnoid hemorrhage (SAH), in whom a good clinical course usually is expected. PATIENTS AND METHODS: We reviewed the clinical data from 141 patients with SAH and 1) initial Hunt & Hess grade 1-3; 2) induction of general anesthesia for intervention; and 3) the presence of data about the functional outcome. Patients were divided into 3 groups: 1) primary tracheotomized patients (PT); 2) patients with successful extubation (ES); and 3) patients with EF (reintubation within 48 hours). RESULTS: EF occurred with a rate of 0.12. The leading cause of EF was respiratory insufficiency (n = 7), followed by impaired consciousness (n = 5). Multivariate logistic regression did not show any neurologic predictor of EF. Patients with ES showed an excellent outcome after 6 months (favorable outcome: 95.7%), whereas the outcome of patients with EF and PT was significantly (P < 0.05) poorer. The case fatality rate was nonsignificantly greater in the EF group (0.15 vs. 0.03). Hospitalization was significantly reduced for patients with ES, whereas the occurrence of symptomatic cerebral vasospasms and vasospastic cerebral infarction was similar between patients with EF, ES, or PT. CONCLUSIONS: We showed that EF is a frequent condition in good grade-SAH but is not predictable using common neurologic parameters. Regarding the functional outcome, we were able to show that the result of an extubation trial clearly delineates the patients in 2 distinct groups, in which ES predicts an excellent outcome.

Repeated Endovascular Treatments in Patients with Recurrent Cerebral Vasospasms After Subarachnoid Hemorrhage: A Worthwhile Strategy?

OBJECTIVE: Endovascular interventions in patients with subarachnoid hemorrhage (SAH) and symptomatic cerebral vasospasm (sCVS) are commonly performed, but the potential benefits of repeated interventions have not been proven. The aim of this study was to show the potential burden and opportunities of repeated endovascular interventions in cases of recurrent sCVS. METHODS: We reviewed 15 patients with SAH who underwent more than 2 endovascular treatments of recurrent sCVS (CVS group) regarding the radiation doses, their clinical course, and their functional outcome. A case-control group of SAH patients without sCVS individually matched for age, World Federation of Neurosurgical Societies score, Fisher grade, and treatment modality was used as control group (non-CVS group). RESULTS: A total of 70 endovascular treatments were performed in the CVS group. CVS group patients received longer mechanical ventilation (585 days vs. 439 days) and showed a higher rate of tracheostomy (12/15 vs. 7/15) and shunt-dependent hydrocephalus (6/15 vs. 2/15) than did the non-CVS patients. Moreover, patients from the CVS group underwent significantly (P < 0.001) more angiographies (median, 5 vs. 2) and CTP/CTA scans (median, 4 vs. 1) and consequently received significantly (P < 0.001) higher radiation doses. The rate of unfavorable outcomes (mRS 3-6) after 3 months was nonsignificantly higher in the CVS group (6/15 vs. 2/15), but after 6 months at least 5/14 patients from the CVS group showed a favorable outcome. CONCLUSION: Repeated endovascular treatments of SAH patients with recurrent CVS are complex and expose the patients to high radiation doses. Nevertheless, favorable results could be achieved in patients in otherwise poor condition.

Safety of Percutaneous Dilatational Tracheostomy in Patients with Acute Brain Injury and Reduced PaO2/FiO2 Ratio-Retrospective Analysis of 54 Patients.

OBJECTIVE: Percutaneous dilatational tracheostomy (PDT) is a commonly performed method in neurocritical care, and its safety has been proven in numerous studies. Nevertheless, data regarding the application in patients with acute brain injury and poor respiratory function are poor. The purpose of this study was to evaluate the incidence of hypoxemia and hypercapnia during PDT in those patients. METHODS: In a retrospective analysis, we acquired data from 54 patients with an acute brain injury (ABI) and a reduced PaO2/FiO2 ratio (PaO2/FiO2 < 300 mm Hg). In all cases, blood gas analyses before, during, and approximately 12 hours after PDT were available. We reviewed the patients' ventilator settings, results of gas exchange, and radiographic signs of acute respiratory distress syndrome (ARDS). Patients with ARDS were defined using the Berlin criteria. RESULTS: We observed 2 cases (3.6%) of intraoperative hypoxemia (PaO2 < 60 mm Hg) and 4 cases (7.4%) of intraoperative hypercapnia (PaCO2 > 55 mm Hg). Twenty patients fulfilled the Berlin criteria for ARDS. While mean PaO2 did not differ significantly between ARDS and non-ARDS patients, intraoperative hypoxemia only occurred in the ARDS group (2/20). Mean PaCO2 was similar in the ARDS and non-ARDS groups, and cases of hypercapnia were apparent in both groups. The mean PaO2/FiO2 ratio of all patients improved from 229.1 mm Hg before PDT to 255.3 mm Hg. CONCLUSIONS: Regarding the intraoperative gas exchange, indication of PDT in patients with ABI and ARDS should be considered carefully. However, PDT in ABI patients with reduced PaO2/FiO2 ratio alone appears to be a safe procedure.

Analysis of extracellular brain chemistry during percutaneous dilational tracheostomy: A retrospective study of 19 patients.

OBJECTIVE: The purpose of this study was to analyze changes in brain tissue chemistry around percutaneous dilational tracheostomy (PDT) in patients with acute brain injury (ABI) in a retrospective single-center analysis. PATIENTS AND METHODS: We included 19 patients who had continuous monitoring of brain tissue chemistry and intracranial pressure (ICP) during a 20h period before and after PDT. Different microdialysis parameters (lactate, pyruvate, lactate pyruvate ratio (LPR), glycerol and glutamate) and values of ICP, cerebral perfusion pressure (CPP) and brain tissue oxygenation (PBrO2) were recorded per hour. Mean values were compared between a 10h period before PDT (prePDT) and after PDT (postPDT). RESULTS: Mean values of cerebral lactate, pyruvate, LPR, glycerol and glutamate did not differ significantly between prePDT and postPDT. In addition, the rate of patients, which exceeded the known threshold was similar between prePDT and postPDT. Only one patient showed a strong increase of cerebral glycerol during the postPDT period, but analysis of subcutaneous glycerol could exclude an intracerebral event. ICP, CPP and PBrO2 did not exhibit significant changes. CONCLUSIONS: We could exclude the occurrence of cerebral metabolic crisis and the excess release of cerebral glutamate and glycerol in a series of 19 patients. Our results support the safety of PDT in patients with ABI.

ERG expression in multiple myeloma-A potential diagnostic pitfall.

INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions. MATERIAL AND METHODS: We subsequently selected 12 formalin-fixed, paraffin-embedded tissue samples of multiple myeloma from our archives and performed immunohistochemical staining for ERG. RESULTS: All 12 analyzed cases showed strong nuclear expression of ERG in >90% of tumor cells (myeloma cells). CONCLUSIONS: This report highlights a potential and critical diagnostic pitfall in biopsy specimens where morphology is only of limited assistance in reaching the correct diagnosis. It urges pathologists to exercise caution in cases where strong ERG-positivity implicates the presence of a prostatic neoplasia and illustrates the need for further immunohistochemical examination.

Isoflurane-Associated Mydriasis Mimicking Blown Pupils in a Patient Treated in a Neurointensive Care Unit.

We report a misinterpretation of bilateral mydriasis as blown pupils related to elevated intracranial pressure (ICP) under volatile sedation with isoflurane (Anesthetic Conserving Device [AnaConDa], Hudson RCI, Uppland Vasby, Sweden) in a 59-year-old patient with a severe traumatic brain injury with frontal contusion. The patient showed bilateral mydriasis and a missing light reflex 8 hours after changing sedation from intravenous treatment with midazolam and esketamine to volatile administration of isoflurane. Because cranial computed tomography ruled out signs of cerebral herniation, we assumed the bilateral mydriasis was caused by isoflurane and reduced the isoflurane supply. Upon this reduction the mydriasis regressed, suggesting the observed mydriasis was related to an overdose of isoflurane. Intensivists should be aware of the reported phenomenon to avoid unnecessary diagnostic investigations that might harm the patient. We recommend careful control of the isoflurane dose when fixed and dilated pupils appear in patients without other signs of elevated ICP.

Microdialysis as a Part of Invasive Cerebral Monitoring During Porcine Septic Shock.

BACKGROUND: Metabolic changes in critically ill patients with endotoxin-induced septic shock are measured primarily by techniques that afford organ-specific metabolic monitoring based on interstitial fluid samples. The present study was designed to evaluate the role of cerebral microdialysis (MD) as a part of invasive neuromonitoring during endotoxemia in a porcine model. MATERIALS AND METHODS: Continuous endotoxin infusion was administered to 7 female pigs and, in addition to hemodynamic monitoring and blood chemistry, interstitial lactate, pyruvate, glucose and glycerol concentrations in muscle, liver, and cerebral tissue were measured via in vivo MD for an observation period of 180 minutes. RESULTS: The cerebral concentrations of lactate and glycerol showed no significant increases, whereas the hepatic and muscular levels rose dramatically under endotoxemia. However, the lactate/pyruvate ratio and especially the lactate/glucose ratio showed a profound and significant increase in brain tissue as well. Cerebral perfusion pressure decreased from 77 to 50 mm Hg without reaching pathologic values. CONCLUSIONS: Although our results confirm the special protection of the brain during endotoxemia compared with other organs, early metabolic changes become evident by increasing lactate/pyruvate ratio and lactate/glucose ratio. MD appears to be a suitable additional technique in invasive neuromonitoring for obtaining early information about metabolic deterioration in the brain during septic shock.

A New Predictive Tool for Optimization of the Treatment of Brain Metastases from Colorectal Cancer After Stereotactic Radiosurgery.

AIM: To develop a predictive tool for survival after stereotactic radiosurgery of brain metastases from colorectal cancer. PATIENTS AND METHODS: Out of nine factors analyzed for survival, those showing significance (p<0.05) or a trend (p≤0.06) were included. For each factor, 0 (worse survival) or 1 (better survival) point was assigned. Total scores represented the sum of the factor scores. RESULTS: Performance status (p=0.010) and interval from diagnosis of colorectal cancer until radiosurgery (p=0.026) achieved significance, extracranial metastases showed a trend (p=0.06). These factors were included in the tool. Total scores were 0-3 points. Six-month survival rates were 17% for patients with 0, 25% for those with 1, 67% for those with 2 and 100% for those with 3 points; 12-month rates were 0%, 0%, 33% and 67%, respectively. Two groups were created: 0-1 and 2-3 points. Six- and 12-month survival rates were 20% vs. 78% and 0% vs. 44% (p=0.002), respectively. CONCLUSION: This tool helps optimize the treatment of patients after stereotactic radiosurgery for brain metastases from colorectal cancer.

PROSAIKA: a prospective multicenter registry with the first programmable gravitational device for hydrocephalus shunting.

OBJECTIVE: Cerebrospinal fluid (CSF) overdrainage is a major problem in shunt therapy for hydrocephalus. The adjustable gravitational valve proSA allows for the first time a targeted compensation for overdrainage in the upright position without interfering with the differential pressure valve. To evaluate benefit, safety and reliability, the multicenter prospective registry PROSAIKA was conducted in 10 German neurosurgical centers. METHODS: Between March 2009 and July 2010, 120 hydrocephalic patients undergoing first time shunt implantation or shunt revision using proSA entered the study. 93 patients completed the 12 months follow-up. RESULTS: Hydrocephalus symptoms were improved in 86%, unchanged in 9% and deteriorated in 3%. In 51%, the proSA opening pressure was readjusted one or several times to treat suspected suboptimal shunt function, this resulted in clinical improvement in 55%, no change in 25%, and deterioration in 20% of these patients. The 1 year censored proSA shunt survival rate was 89%. Device related shunt failure was seen in two cases. CONCLUSIONS: This is the first clinical report on the implantation of the adjustable gravitational valve proSA with a follow-up of 12 months in a substantial number of patients. Irrespective of different hydrocephalus etiologies and indications for shunt surgery, the overall results after 12 months were very satisfying. The high frequency of valve readjustments underlines the fact that preoperative selection of the appropriate valve opening pressure is difficult. The low number of revisions and complications compared to other valves proves that proSA implantation adds no further risk; this valve is reliable, helpful and safe.

Impact of percutaneous dilatational tracheostomy in brain injured patients.

OBJECTIVE: Tracheostomy is an established method in the airway management of critically ill patients with traumatic and non-traumatic brain injuries. High priority in the treatment of those patients is to protect vulnerable brain tissue. While bedside percutaneously dilatative tracheostomy (PDT) technique is increasingly used, there is disagreement about the harms of this intervention for the damaged brain. Therefore, discussions about the safety of tracheostomy in those patients must consider direct and indirect cerebral parameters. METHODS: We examined a series of 289 tracheostomies regarding vital signs, respiratory and intracranial parameters in a retrospective study. Complications were recorded and risk factors for a complicated scenario statistically determined. RESULTS: Severe complications were rare (1/289). Arterial hypotension occurred in 3 of 289 cases with a systolic blood pressure below 90mmHg. We had two patients (0.5%) with transient hypoxia, but 43 cases (15%) of severe hypercapnia during PDT. Invasive measurement of brain tissue oxygen tension (PBrO2) ruled out any cerebral hypoxia during the procedure in 39 available cases. Intracranial pressure (ICP) rose temporarily in 24% of the cases. Cerebral perfusion pressure (CPP) however remained unaffected. Surgery time and hypercapnia are capable risk factors for intraoperative ICP elevation. There is no significant difference in intraoperative ICP rises between disease entities. CONCLUSION: PDT is a safe procedure for the most common neurosurgical diseases, even for patients with respiratory insufficiency. Shortening surgical time seems to be the most important factor to avoid ICP increase.

Predicting overall survival in patients with brain metastases from esophageal cancer.

AIM: To identify survival predictors and develop a survival score for patients with brain metastases from esophageal cancer. PATIENTS AND METHODS: In 16 patients, seven factors were analyzed including age, gender, Karnofsky performance score (KPS), time from diagnosis of esophageal cancer to irradiation, number of brain metastases, histology, and presence of extracerebral metastases. RESULTS: Improved survival was significantly associated with KPS≥80 (p<0.001), the presence of one brain metastasis (p=0.007), and no extra-cerebral metastases (p=0.002). These factors were included in the final score. Factor scores were calculated by dividing 6-month survival rates by 10. Total survival scores represented the sums of factor scores and were 2, 7, 10, 19 or 24 points. Six-month survival rates by score were 0%, 0%, 0%, 67% and 100%, respectively. Two groups were formed, those of patients with 2-10 points and those with 19-24 points; 6-month survival was 0% and 88%, respectively (p<0.001). CONCLUSION: This new score facilitates the selection of individual therapies for patients with brain metastases from esophageal cancer.

Radiosurgery alone for 1-3 newly-diagnosed brain metastases from melanoma: impact of dose on treatment outcomes.

BACKGROUND/AIM: To compare different doses of stereotactic radiosurgery (SRS) for 1-3 newly-diagnosed cerebral metastases from melanoma. PATIENTS AND METHODS: Fifty-four patients were assigned to dose groups of 20 Gy (N=36) and 21-22.5 Gy (N=18). Variables additionally analyzed were age, gender, Karnofsky Performance Score (KPS), lactate dehydrogenase (LDH) before SRS, number of cerebral lesions, extracranial lesions, time from melanoma diagnosis to SRS. RESULTS: The 12-month local control was 72% after 20 Gy and 100% after 21-22.5 Gy (p=0.020). Freedom from new cerebral metastases (p=0.13) and survival (p=0.13) showed no association with SRS dose. On multivariate analyses, improved local control showed significant associations with SRS doses of 21-22.5 Gy (p=0.007) and normal lactate dehydrogenase levels (p=0.018). Improved survival was associated with normal LDH levels (p=0.006) and KPS 90-100 (p=0.046). CONCLUSION: SRS doses of 21-22.5 Gy resulted in better local control than 20 Gy. Freedom from new brain metastases and survival were not significantly different.

Cerebral metabolism during experimental endotoxin shock and after preconditioning with monophosphoryl lipid A.

PURPOSE: Preconditioning with low doses of monophosphoryl lipid A (MPL) has been shown to induce endotoxin tolerance and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, no data are available about the effects of endotoxin preconditioning on cerebral metabolism during endotoxemia. The study was designed to determine the effects of endotoxin preconditioning with MPL on cerebral metabolism via microdialysis compared to muscle tissue metabolism during experimental endotoxemia. METHODS: In a controlled animal study, continuous endotoxin infusion (1µg/kg b.w. per h) was administrated to 7 female mixed-breed pigs after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. In the control group, 7 animals received a saline pretreatment. In addition to hemodynamic monitoring and blood gas analyses, interstitial lactate, pyruvate, glucose and glycerol concentrations in muscle and cerebral tissue were measured using in vivo microdialysis. RESULTS: There were no significant differences between the two groups with respect to hemodynamic parameters, while mixed venous oxygen saturation (SvO2), arterial blood pH and mean pulmonary arterial pressure (MPAP) were significantly higher in the preconditioned group. Cerebral perfusion pressure (CPP) and brain tissue oxygen pressure (ptiO2) values stayed stable throughout the experiment with no inter-group differences. While interstitial concentrations of lactate and glycerol as well as the lactate/pyruvate (LP) and the lactate/glucose (LG) ratio in muscle tissues were significantly increased in control animals compared to those who had been pretreated with MPL; the results of cerebral microdialysis showed no significant changes in interstitial lactate or glycerol levels in both groups. However, the lactate/glucose (LG) ratio in the control group showed a significantly higher increase than in the preconditioned group. CONCLUSIONS: Preconditioning with low doses of MPL ameliorates the negative metabolic effects of endotoxin shock in muscle tissue. With regard to cerebral metabolism, the present study suggests that MLP preconditioning provides moderate advantages, at least in an experimental model of endotoxin shock.