Expression of peptide transporter 1 has a positive correlation in protoporphyrin IX accumulation induced by 5-aminolevulinic acid with photodynamic detection of non-small cell lung cancer and metastatic brain tumor specimens originating from non-small cell lung cancer.

BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be a useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.

Efficacy of the All-in-One Therapeutic Strategy for Severe Traumatic Brain Injury: Preliminary Outcome and Limitation / 대한신경손상학회지

OBJECTIVE: Despite recent advances in medicine, no significant improvement has been achieved in therapeutic outcomes for severe traumatic brain injury (TBI). In the treatment of severe multiple traumas, accurate judgment and prompt action corresponding to rapid pathophysiological changes are required. Therefore, we developed the “All-in-One” therapeutic strategy for severe TBI. In this report, we present the therapeutic concept and discuss its efficacy and limitations. METHODS: From April 2007 to December 2015, 439 patients diagnosed as having traumatic intracranial injuries were treated at our institution. Among them, 158 patients were treated surgically. The “All-in-One” therapeutic strategy was adopted to enforce all selectable treatments for these patients at the initial stages. The outline of this strategy is as follows: first, prompt trepanation surgery in the emergency room (ER); second, extensive decompression craniotomy (DC) in the operating room (OR); and finally, combined mild hypothermia and moderate barbiturate (H-B) therapy for 3 to 5 days. We performed these approaches on a regular basis rather than stepwise rule. If necessary, internal ecompression surgery and external ventricular drainage were performed in cases in which intracranial pressure could not be controlled. RESULTS: Trepanation surgery in the ER was performed in 97 cases; among these cases, 46 had hematoma removal surgery and also underwent DC in the OR. Craniotomy was not enforced unless the consciousness level and pupil findings did not improve after previous treatments. H-B therapy was administered in 56 cases. Internal decompression surgery, including evacuation of traumatic intracerebral hematoma, was additionally performed in 12 cases. Three months after injury, the Glasgow Outcome Scale (GOS) score yielded the following results: good recovery in 25 cases (16%), mild disability in 28 (18%), severe disability in 33 (21%), persistent vegetative state in 9 (6%), and death in 63 (40%). Furthermore, 27 (36%) of the 76 most severe patients who had an abnormal response of bilateral eye pupils were life-saving. Because many cases of a GOS score of ≤5 are included in this study, this result must be satisfactory. CONCLUSION: This therapeutic strategy without any lose in the appropriate treatment timing can improve the outcomes of the most severe TBI cases. We think that the breakthrough in the treatment of severe TBI will depend on the shift in the treatment policy.

Glioblastoma Multiforme in the Pineal Region with Leptomeningeal Dissemination and Lumbar Metastasis

We report a case of a 31-year-old woman with glioblastoma multiforme (GBM) in the pineal region with associated leptomeningeal dissemination and lumbar metastasis. The patient presented with severe headache and vomiting. Magnetic resonance imaging (MRI) of the brain showed a heterogeneously enhanced tumor in the pineal region with obstructive hydrocephalus. After an urgent ventricular-peritoneal shunt, she was treated by subtotal resection and chemotherapy concomitant with radiotherapy. Two months after surgery, MRI showed no changes in the residual tumor but leptomeningeal dissemination surrounding the brainstem. One month later, she exhibited severe lumbago and bilateral leg pain. Thoracico-lumbar MRI showed drop like metastasis in the lumbar region. Finally she died five months after the initial diagnosis. Neurosurgeons should pay attention to GBM in the pineal region, not only as an important differential diagnosis among the pineal tumors, but due to the aggressive features of leptomeningeal dissemination and spinal metastasis.