FFPE++: Improving the quality of formalin-fixed paraffin-embedded tissue imaging via contrastive unpaired image-to-image translation.

Formalin-fixation and paraffin-embedding (FFPE) is a technique for preparing and preserving tissue specimens that has been utilized in histopathology since the late 19th century. This process is further complicated by FFPE preparation steps such as fixation, processing, embedding, microtomy, staining, and coverslipping, which often results in artifacts due to the complex histological and cytological characteristics of a tissue specimen. The term "artifacts" includes, but is not limited to, staining inconsistencies, tissue folds, chattering, pen marks, blurring, air bubbles, and contamination. The presence of artifacts may interfere with pathological diagnosis in disease detection, subtyping, grading, and choice of therapy. In this study, we propose FFPE++, an unpaired image-to-image translation method based on contrastive learning with a mixed channel-spatial attention module and self-regularization loss that drastically corrects the aforementioned artifacts in FFPE tissue sections. Turing tests were performed by 10 board-certified pathologists with more than 10 years of experience. These tests which were performed for ovarian carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, and papillary thyroid carcinoma, demonstrate the clear superiority of the proposed method in many clinical aspects compared with standard FFPE images. Based on the qualitative experiments and feedback from the Turing tests, we believe that FFPE++ can contribute to substantial diagnostic and prognostic accuracy in clinical pathology in the future and can also improve the performance of AI tools in digital pathology. The code and dataset are publicly available at https://github.com/DeepMIALab/FFPEPlus.

New missions for an old agent: granulocyte-colony stimulating factor in the treatment of stroke patients.

Granulocyte-colony stimulating factor (G-CSF) has a multimodal neuroprotective profile and the cumulative preclinical data from numerous translational studies statistically confirmed the efficacy of G-CSF as a treatment option in ischemic stroke. G-CSF activates anti-apoptotic, antioxidative, and anti-inflammatory signaling pathways and stimulates angiogenesis and neurogenesis. In this review, we summarize the role of G-CSF and the corresponding signal transduction pathways regulated by G-CSF in neuroprotection and discuss its potential as a new drug for stroke treatment.

Health transformation project and defensive medicine practice among neurosurgeons in Turkey.

BACKGROUND: The term "Defensive" medicine was coined in the early 1970's and has been an important topic of scientific investigation and professional debate ever since. OBJECTIVE: The aim of this study was to investigate the characteristics of defensive medicine, its reasons, and the extent to which it is practiced in the Turkish health care system. This is the first national survey to study the practice of defensive medicine among neurosurgeons in Turkey. METHODS: The present cross-sectional study on defensive medicine assessed neurosurgeons registered at the Turkish Neurosurgical Society, who are actively working in various centers and hospitals within the Turkish health care system. A 40-question survey was adapted from existing measures described in the literature and was completed by a total of 404 neurosurgeons, representing 36.7% of the neurosurgeons registered at the Turkish Neurosurgical Society. RESULTS: Seventy-two percent of the participants in the current study reported practicing defensive medicine. This practice was mainly reported among inexperienced neurosurgeons (74.4%). Most were younger than 40 years of age (75.2%), working in state hospitals/universities (72.7%), and living in the Marmara region (38%). Respondents reported engaging in defensive medicine by avoiding high-risk surgery (62.6%), ordering additional imaging studies (60.9%) and laboratory tests (33.7%), and referring patients to consultants (31.2%). Most participants consider every patient as a potential threat in terms of a medical lawsuit (68.3%) and do not believe the courts can distinguish malpractice from complications (89.6%). CONCLUSION: Concerns and perceptions about medical liability lead neurosurgeons to practice defensive medicine. By avoiding high-risk surgery, ordering unnecessary diagnostic tests, and referring the patients to consultants, neurosurgeons try to minimize the risk of malpractice and protect themselves from legal risks, resulting in higher healthcare expenditure and longer treatment periods.

Bronchogenic cyst of the craniocervical junction: a case report.

Intracranial bronchogenic cysts (BCs) are uncommon, and BCs at the craniocervical junction are extremely rare. These lesions are most frequently encountered in the cervico-thoracic region of the spine. Their pathogenesis is still poorly understood. Regardless of the surgical approach, the aim of surgery should be total removal of the cyst and its content, whenever feasible. In this case report, a 50-year-old patient with a BC of the craniocervical junction is presented. The patient was operated on through a right-sided suboccipital retrosigmoid approach. The uniform layer of pseudostratified, ciliated and mucus-secreting columnar cells was seen on histological examination. The clinical manifestations, diagnosis, and treatment of this unusual condition are discussed.

Seizure characteristics and control following resection in 332 patients with low-grade gliomas.

OBJECT: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS: The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS: Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). CONCLUSIONS: The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.

Volumetric extent of resection and residual contrast enhancement on initial surgery as predictors of outcome in adult patients with hemispheric anaplastic astrocytoma.

OBJECT: To investigate the prognostic significance of the volumetrically assessed extent of resection on time to tumor progression (TTP), overall survival (OS), and tumor recurrence patterns, the authors retrospectively analyzed preoperative and postoperative tumor volumes in 102 adult patients from the time of the initial resection of a hemispheric anaplastic astrocytoma (AA). METHODS: The quantification of tumor volumes was based on a previously described method involving computerized analysis of magnetic resonance (MR) images. Analysis of contrast-enhancing tumor volumes on T1-weighted MR images was conducted for 67 patients who had contrast-enhancing tumors. Measurements of T2 hyperintensity were obtained for all 102 patients in the study. The presence or absence of preresection enhancement, actual volume of this enhancement, and the percentage of preoperative enhancement as it relates to the total T2 tumor volume did not have a statistically significant relationship to TTP or OS. In addition to age, the volume of residual disease measured on T2-weighted MR images was the most significant predictor of TTP (p < 0.001), and residual contrast-enhancing tumor volume was the most significant predictor of OS (p = 0.003) on multivariate analysis. In contrast to low-grade gliomas, there was no statistically significant relationship between the extent of resection and histological characteristics at the time of recurrence, that is, tumor Grade III compared with Grade IV. CONCLUSIONS: Data from this retrospective analysis of a histologically uniform group of hemispheric AAs treated in the MR imaging era suggest that residual tumor volumes, as documented on postoperative imaging studies, may be a prognostic factor for TTP and OS for this patient population.

Definition and diagnostic implications of gemistocytic astrocytomas: a pathological perspective.

Gemistocytic astrocytoma still continues to be enigmatic; both in terms of definition and prognostic implications. The major issue of contention has been the clinical relevance of this pathological entity. The currently accepted definition of gemistocytic astrocytoma requires 20% or more gemistocytes, and considers the neoplasm as a diffuse astrocytoma, which is a WHO grade II tumor. Some suggest that gemistocytic morphology should be considered as evidence of a higher grade astrocytoma. However, there is no consensus on the percentage of gemistocytes associated with a worse prognosis than otherwise expected. Given the reported cases and series, it is not clear that this morphology portends a more aggressive biology when all else is equal. There is still a need for studies with sufficient numbers of well-matched gemistocytic and non-gemistocytic astrocytic neoplasms to decide whether upgrading a tumor with 'significant' number of gemistocytes is justifiable. This article presents a critical review of the existing studies and a brief mention of our experience from a pathological perspective.

Advances in neurosurgical technique in the current management of brain tumors.

Despite significant advances in anatomical and functional neuroimaging modalities (eg, magnetic resonance [MR] imaging [MRI], MR spectroscopy [MRS], diffusion and perfusion MR, functional MRI [fMRI], magnetic-source imaging [MSI], diffusion tensor imaging [DTI]) and neuronavigation techniques, intraoperatively obtained functional information remains of crucial importance to the neurosurgeon, especially when operating on tumors that are located in or adjacent to functional cortical sites and subcortical pathways. This article focuses on recent advances in the surgical management of of intracerebral tumors with special emphasis on intraoperative cortical and subcortical stimulation mapping methods, and the prognostic significance of surgery on patient outcome.

Intracranial neuronavigation with intraoperative magnetic resonance imaging.

PURPOSE OF REVIEW: This is an invited review regarding the use of intraoperative magnetic resonance imaging in the neurosurgical setting. The medical literature evaluating the intraoperative use of magnetic resonance imaging for neurosurgery has increased steadily since the implementation of this technique 10 years ago. The present review discusses recent findings and the current use of intraoperative magnetic resonance imaging in neurosurgery with special emphasis on the quality of available evidence. RECENT FINDINGS: Intraoperative use of magnetic resonance imaging is a safe technique that enables the neurosurgeon to update data sets for navigational systems, to evaluate the extent of tumor resection and modify surgery if necessary, to guide instruments to the site of the lesion, and to evaluate the presence of intraoperative complications at the end of surgery. Although recent findings support the safety and efficacy of intraoperative magnetic resonance imaging for the above-mentioned purposes, there is no convincing evidence regarding its prognostic significance in the neurosurgical setting. SUMMARY: Although the use of intraoperative magnetic resonance imaging in neurosurgery has increased significantly within the last 10 years, currently there are less than two dozen dedicated intraoperative units in the United States. The popularization of this technique depends on both economic justification and high-quality scientific evidence supporting its prognostic importance regarding patient outcome.

Intraoperative subcortical stimulation mapping for hemispherical perirolandic gliomas located within or adjacent to the descending motor pathways: evaluation of morbidity and assessment of functional outcome in 294 patients.

OBJECT: Intraoperative stimulation mapping of subcortical white matter tracts during the resection of gliomas has become a valuable surgical adjunct that is used to reduce morbidity associated with tumor removal. The purpose of this retrospective analysis was to assess the morbidity and functional outcome associated with this method, thus allowing the surgeon to predict the likelihood of causing a temporary or permanent motor deficit. METHODS: In this study, the authors report their experience with intraoperative stimulation mapping to locate subcortical motor pathways in 294 patients who underwent surgery for hemispheric gliomas within or adjacent to the rolandic cortex. Data were collected regarding intraoperative cortical and subcortical stimulation mapping results, along with the patient's neurological status pre- and postoperatively. For patients in whom an additional motor deficit occurred postoperatively, its evolution was examined. Of 294 patients, an additional postoperative motor deficit occurred in 60 (20.4%). Of those 60, 23 (38%) recovered to their preoperative baseline status within the 1st postoperative week. Another 12 (20%) recovered from their postoperative motor deficit by the end of the 4th postoperative week, and 11 more recovered to their baseline status by the end of the 3rd postoperative month. Thus, 46 (76.7%) of 60 patients with postoperative motor deficits regained their baseline function within the first 90 days after surgery. The remaining 14 patients (4.8% of the entire study population of 294) had a persistent motor deficit after 3 months. Patients whose subcortical pathways were identified with stimulation mapping were more prone to develop an additional (temporary or permanent) motor deficit than those in whom subcortical pathways could not be identified (27.5% compared with 13.1%, p = 0.003). This was also true when additional (permanent) motor deficits lasted more than 3 months (7.4% when subcortical pathways were found, compared with 2.1% when they were not found; p = 0.041). CONCLUSIONS: In patients with gliomas that are located within or adjacent to the rolandic cortex and, thus, the descending motor tracts, stimulation mapping of subcortical pathways enables the surgeon to identify these descending motor pathways during tumor removal and to achieve an acceptable rate of permanent morbidity in these high-risk functional areas.

Volume of residual disease as a predictor of outcome in adult patients with recurrent supratentorial glioblastomas multiforme who are undergoing chemotherapy.

OBJECT: For patients with recurrent glioblastomas multiforme (GBMs) the prognosis is poor. Although chemotherapy may provide a survival advantage, the role of the extent of tumor resection, or the volume of the residual tumor at the time of recurrence, before instituting chemotherapy, is unclear. This study was designed to assess the response to chemotherapy based on the volume of residual disease (VRD) at the start of treatment in patients with recurrent GBMs. To accomplish this, the authors evaluated a homogeneous group of patients with recurrent GBMs who received the same chemotherapeutic agent. METHODS: One hundred nineteen adult patients with recurrent supratentorial GBMs received temozolomide chemotherapy at the time of tumor recurrence. In this cohort the authors analyzed the prognostic significance of volumetrically assessed tumor mass on time to tumor progression (TTP) and survival time (ST). Multivariate analysis demonstrated that the VRD at the beginning of chemotherapy was a statistically significant predictor of both TTP (p < 0.0001) and ST (p < 0.006) when adjusted for the patient's age, performance score, and time from the initial diagnosis. Patients in whom the VRD was less than 10 cm3 at the start of chemotherapy had a 6-month progression-free survival rate of 32% compared with 8% for patients with a VRD between 10 and 15 cm3 and 3% for patients with a VRD larger than 15 cm3. Patients in whom the VRD was smaller than 10 cm3 had a 1-year survival rate of 37% compared with 9% for patients with a VRD between 10 and 15 cm3 and 18% for patients with a VRD larger than 15 cm3. CONCLUSIONS: These data indicate that patients with recurrent GBMs who start chemotherapy with a smaller volume (< 10 cm3) of residual disease may have a more favorable response to chemotherapy and a more favorable outcome.

Treatment of progressive or recurrent glioblastoma multiforme in adults with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration: a phase I/II multi-institutional trial.

To determine the safety and evaluate the efficacy of repeated administration of virus-producing cells (GLI 328) containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent glioblastoma multiforme, we conducted a phase I/II multi-institutional trial. Eligible patients underwent surgical resection of tumor, followed by injections of vector producing cells (VPC) into the brain adjacent to the cavity. An Ommaya reservoir placed after surgery was used to inject a further dose of VPC seven days after surgery, followed seven days later by ganciclovir. Further gene therapy was given at 28-day intervals for up to a total of five cycles. Toxicity and anti-tumor effect were assessed. Of 30 patients who enrolled in the study, 16 experienced serious adverse events possibly related to the experimental therapy. Laboratory testing, including polymerase chain reaction analysis to detect replication-competent retrovirus in peripheral blood lymphocytes and tissues, as well as co-cultivation bioassays, were negative. Before receiving ganciclovir, 37% of the patients showed evidence of transduced peripheral blood leukocytes, but only 12% showed a persistence of transduced cells at the end of the first cycle of ganciclovir. Median survival was 8.4 months. Twenty percent of the patients (n = 6) survived more than 12 months from the date of study entry. This treatment modality is feasible and appears to have some evidence of efficacy. Toxicity may be related in part to the method of gene delivery.

Coregistration accuracy and detection of brain shift using intraoperative sononavigation during resection of hemispheric tumors.

OBJECTIVE: Sononavigation, which combines real-time anatomic ultrasound data with neuronavigation techniques, is a potentially valuable adjunct during the surgical excision of brain tumors. METHODS: In this study, we report our preliminary observations using this technology on 58 adult patients harboring hemispheric tumors. Data regarding coregistration accuracy was collected from various landmarks that typically do not shift as well as from tumor boundaries and the cortical surface. In a subset of patients, we evaluated the extent and direction of postresection brain displacement and its relationship with patient age, tumor histology, tumor volume, and use of mannitol. RESULTS: For all structures excluding the cortex, average coregistration accuracy measurements between ultrasound and preoperatively acquired magnetic resonance imaging scans were within the range of 2 mm. The most accurate alignments were obtained with the choroid plexus and the falx, and the least reliable structure in terms of coregistration accuracy was the cortical surface. CONCLUSION: Sononavigation provides real-time information during tumor removal in alignment with the preoperative magnetic resonance imaging scans, thus enabling the surgeon to detect intraoperative hemorrhage, cyst drainage, and tumor resection, and it allows for calculation of brain shift during the use of standard navigation techniques.