Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl 4 -induced model of reversible hepatic fibrosis to identify and characterize ...the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B hi F4/80 int Ly-6C lo macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C hi monocytes, a common origin with profibrotic Ly-6C hi macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C lo subset, compared with Ly-6C hi macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process.
Aggressive pituitary adenomas (APAs) are pituitary tumors that are refractory to standard treatments and carry a poor prognosis. Current treatment guidelines are not standardized but combine surgical ...resection, radiation therapy, and chemotherapy. Temozolomide is the only chemotherapeutic agent with documented effectiveness and is recommended for APA in European Society of Endocrinology clinical guidelines.
A 57-year-old man presented with visual deterioration and bitemporal hemianopsia. MRI of the brain demonstrated a sellar mass suspected to be pituitary macroadenoma with displacement of the stalk and optic nerve impingement. The patient underwent stereotactic endoscopic transsphenoidal resection of the mass. Postoperative MRI demonstrated gross total resection. Pathology revealed a sparsely granulated corticotroph adenoma with malignant transformation. Immunohistochemistry showed loss of expression of MLH1 and PMS2 in the tumor cells. Proton therapy was recommended given an elevated Ki67 index and p53 positivity. Before radiotherapy, there was no radiographic evidence of residual tumor. Temozolomide therapy was initiated after surveillance MRI showed recurrence at 16 months postoperatively. However, MRI demonstrated marked progression after 3 cycles. Next-generation sequencing using the MSK-IMPACT platform identified somatic mutations in MLH1 Y548lfs*9 and TP53 R337C . Immunotherapy with ipilimumab/nivolumab was initiated, and MRI demonstrated no residual tumor burden 34 months postoperatively.
APA is a tumor with frequent recurrence and a short median expected length of survival. Here, we demonstrate the utility of immunotherapy in a single case report of APA, with complete resolution of recurrent APA and improved survival compared with life expectancy.
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults ...with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 10
, 10
or up to 10
cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.
Gross-total resection (GTR) of craniopharyngiomas (CPs) is potentially curative and is often the goal of surgery, but endocrinopathy generally results if the stalk is sacrificed. In some cases, GTR ...can be attempted while still preserving the stalk; however, stalk manipulation or devascularization may cause endocrinopathy and this strategy risks leaving behind small tumor remnants that can recur.
A retrospective review of a prospective cohort of patients who underwent initial resection of CP using the endoscopic endonasal approach over a period of 12 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, was performed. Postresection integrity of the stalk was retrospectively assessed using operative notes, videos, and postoperative MRI. Tumors were classified based on location into type I (sellar), type II (sellar-suprasellar), and type III (purely suprasellar). Pre- and postoperative endocrine function, tumor location, body mass index, rate of GTR, radiation therapy, and complications were reviewed.
A total of 54 patients who had undergone endoscopic endonasal procedures for first-time resection of CP were identified. The stalk was preserved in 33 (61%) and sacrificed in 21 (39%) patients. GTR was achieved in 24 patients (73%) with stalk preservation and 21 patients (100%) with stalk sacrifice (p = 0.007). Stalk-preservation surgery achieved GTR and maintained completely normal pituitary function in only 4 (12%) of 33 patients. Permanent postoperative diabetes insipidus was present in 16 patients (49%) with stalk preservation and in 20 patients (95%) following stalk sacrifice (p = 0.002). In the stalk-preservation group, rates of progression and radiation were higher with intentional subtotal resection or near-total resection compared to GTR (67% vs 0%, p < 0.001, and 100% vs 12.5%, p < 0.001, respectively). However, for the subgroup of patients in whom GTR was achieved, stalk preservation did not lead to significantly higher rates of recurrence (12.5%) compared with those in whom it was sacrificed (5%, p = 0.61), and stalk preservation prevented anterior pituitary insufficiency in 33% and diabetes insipidus in 50%.
While the decision to preserve the stalk reduces the rate of postoperative endocrinopathy by roughly 50%, nevertheless significant dysfunction of the anterior and posterior pituitary often ensues. The decision to preserve the stalk does not guarantee preserved endocrine function and comes with a higher risk of progression and need for adjuvant therapy. Nevertheless, to reduce postoperative endocrinopathy attempts should be made to preserve the stalk if GTR can be achieved.
We describe a patient with symptomatic os odontoideum and a previous history of C1-2 wiring who underwent successful treatment with a staged endonasal odontoidectomy and C1-2 revision of ...instrumentation. Access to the odontoid process was gained through the endonasal corridor using an inverted U-shaped nasopharyngeal flap (IUNF). Post-operatively, the patient experienced resolution of her presenting neurologic symptoms but developed conductive hearing loss secondary to bilateral middle ear effusion, requiring bilateral myringotomy and tube placement 3 months post-operatively. We hypothesize this dysfunction may have resulted from surgical edema, packing buttressing the IUNF, or some combination thereof. In this manuscript, we review the evolution of the nasopharyngeal exposure for odontoidectomy and whether an IUNF may predispose to this complication.
Intrinsic third ventricular craniopharyngiomas (IVCs) have been reported by some authors to "pose the greatest surgical challenge" of all craniopharyngiomas (CPAs). A variety of open microsurgical ...approaches have historically been used for resection of these tumors. Despite increased utilization of the endoscopic endonasal approach (EEA) for resection of CPAs in recent years, many authors continue to recommend against use of the EEA for resection of IVCs. In this paper, the authors present the largest series to date utilizing the EEA to remove IVCs.
The authors reviewed a prospectively acquired database of the EEA for resection of IVCs over 14 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital. Preoperative MR images were examined independently by two neurosurgeons and a neuroradiologist to identify IVCs. Pre- and postoperative endocrinological, ophthalmological, radiographic, and other morbidities were determined from retrospective chart review and volumetric radiographic analysis.
Between January 2006 and August 2017, 10 patients (4 men, 6 women) ranging in age from 26 to 67 years old, underwent resection of an IVC utilizing the EEA. Preoperative endocrinopathy was present in 70% and visual deterioration in 60%. Gross-total resection (GTR) was achieved in 9 (90%) of 10 patients, with achievement of near-total (98%) resection in the remaining patient. Pathology was papillary in 30%. Closure incorporated a "gasket-seal" technique with nasoseptal flap coverage and either lumbar drainage (9 patients) or a ventricular drain (1 patient). Postoperatively, complete anterior and posterior pituitary insufficiency was present in 90% and 70% of patients, respectively. In 4 patients with normal vision prior to surgery, 3 had stable vision following tumor resection. One patient noted a new, incongruous, left inferior homonymous quadrantanopsia postoperatively. In the 6 patients who presented with compromised vision, 2 reported stable vision following surgery. Each of the remaining 4 patients noted significant improvement in vision after tumor resection, with complete restoration of normal vision in 1 patient. Aside from the single case (10%) of visual deterioration referenced above, there were no instances of postoperative neurological decline. Postoperative CSF leakage occurred in 1 morbidly obese patient who required reoperation for revision of closure. After a mean follow-up of 46.8 months (range 4-131 months), tumor recurrence was observed in 2 patients (20%), one of whom was treated with radiation and the other with chemotherapy. Both of these patients had previously undergone GTR of the IVC.
The 10 patients described in this report represent the largest number of patients with IVC treated using EEA for resection to date. EEA for resection of IVC is a safe and efficacious operative strategy that should be considered a surgical option in the treatment of this challenging subset of tumors.
Patients who present with a large colloid cyst (CC) and nondilated ventricles represent a therapeutic challenge.1-3 Although transcallosal approaches provide reliable access to the lateral ventricle ...and foramen of Monro, direct visualization of the vascular attachment of the CC to the roof of the third ventricle is not always possible. This can be especially true with CCs located more posteriorly and superiorly.4 Opening of the choroidal fissure can improve access and visualization to the posterior third ventricle; however, this maneuver is associated with some element of risk.5 There is a paucity of operative video in the literature illustrating the technique of gentle, microblade elevation of the fornix to improve visualization into the third ventricle and, on occasion, avoid the need to open the choroidal fissure.6 We report the case of a 28-year-old woman who presented with headaches and progressive short-term memory dysfunction (Video 1). Magnetic resonance imaging demonstrated a 17-mm CC associated with distortion and thinning of the bilateral fornices without hydrocephalus. The patient was offered interhemispheric, transcallosal resection. Intraoperatively, gentle elevation of the fornix with a microblade retractor facilitated access to the vascular attachment of the colloid cyst—obviating the need to open the choroidal fissure. The index operative video discusses the technical nuances associated with trans-callosal resection of CC with use of the microblade retractor. Special emphasis is placed on the intricate relationship of neighboring anatomic structures. The patient consented to the procedure and the publication of her image.
OBJECTIVEActive-duty neurosurgical coverage has been provided at Bagram Air Force Base in Afghanistan since 2007. Early operative logs were reflective of a large number of surgical procedures ...performed to treat battlefield injuries. However, with maturation of the war effort, the number of operations for battlefield injuries has decreased with time. Consequently, procedures performed for elective neurosurgical humanitarian care (NHC) increased in number and complexity prior to closure of the Korean Hospital in 2015, which resulted in effective termination of NHC at Bagram. Monthly neurosurgical caseloads for deployed personnel have dropped precipitously since this time, renewing a debate as to whether the benefits of providing elective NHC in Afghanistan outweigh the costs of such a strategy. To date, there is a paucity of information in the literature discussing the overall context of such a determination.METHODSThe author retrospectively reviewed his personal database of all patients who underwent neurosurgical procedures at Bagram during his deployment there from April 17 to October 29, 2014. Standardized clinical parameters had been recorded in the ABNS NeuroLog system. All cases of nonelective surgical care for battlefield injuries were identified and excluded. Records of all other procedures, which represented elective NHC delivered during this period, were accessed to extract salient clinical and radiological data.RESULTSDuring the 6-month deployment, 49 patients (29 male and 20 female, age range 18 months to 63 years) were treated by the author in elective NHC. Procedures were performed for spinal degenerative disease (n = 28), cranial tumors (n = 11), pediatric conditions (n = 6), Pott's disease (n = 2), peripheral nerve impingement (n = 1), and adult hydrocephalus (n = 1). The duration of follow-up ranged from 3 to 23 weeks. Complications referable to surgery included asymptomatic, unilateral lumbar screw fracture detected 3 months postoperatively and treated with revision of hardware (n = 1); wound infection requiring cranial flap explantation and staged cranioplasty (n = 1); and unanticipated return to the operating room for resection of residual tumor in a patient with a solitary metastatic lesion involving the mesial temporal lobe/ambient cistern (n = 1). There were no instances of postoperative neurological decline.CONCLUSIONSElective NHC can be safely and effectively implemented in the deployed setting. Benefits of a military strategy that supports humanitarian care include strengthening of the bond between the US/Afghan military communities and the local civilian population as well as maintenance of skills of the neurosurgical team during the sometimes-lengthy intervals between cases in which emergent neurosurgical care is provided for treatment of battlefield injuries.
Purpose
Odontoidectomy for ventral compressive pathology may result in O-C1 and/or C1-2 instability. Same-stage endonasal C1-2 spinal fusion has been advocated to eliminate risks associated with ...separate-stage posterior approaches. While endonasal methods for C1 instrumentation and C1-2 trans-articular stabilization exist, no hypothetical construct for endonasal occipital instrumentation has been validated. We provide an anatomic description of anterior occipital condyle (AOC) screw endonasal placement as proof-of-concept for endonasal craniocervical stabilization.
Methods
Eight adult, injected cadaveric heads were studied for placing 16 AOC screws endonasally. Thin-cut CT was used for registration. After turning a standard inferior U-shaped nasopharyngeal flap endonasally, 4 mm × 22 mm AOC screws were placed with a 0° driver using neuronavigation. Post-placement CT scans were obtained to determine: site-of-entry, measured from the endonasal projection of the medial O-C1 joint; screw angulation in sagittal and axial planes, proximity to critical structures.
Results
Average site-of-entry was 6.88 mm lateral and 9.74 mm rostral to the medial O-C1 joint. Average angulation in the sagittal plane was 0.16° inferior to the palatal line. Average angulation in the axial plane was 23.97° lateral to midline. Average minimum screw distances from the jugular bulb and hypoglossal canal were 4.80 mm and 1.55 mm.
Conclusion
Endonasal placement of AOC screws is feasible using a 0° driver. Our measurements provide useful parameters to guide optimal placement. Given proximity of hypoglossal canal and jugular bulb, neuronavigation is recommended. Biomechanical studies will ultimately be necessary to evaluate the strength of AOC screws with plate-screw constructs utilizing endonasal C1 lateral mass or C1-2 trans-articular screws as inferior fixation points.
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