We identified 3 types of spontaneous spinal CSF leak in this observational study: the dural tear, the meningeal diverticulum, and the CSF-venous fistula. These 3 types and the presence or absence of extradural CSF form the basis of a comprehensive classification system.

Purpose Current staging systems for oral cavity cancers incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigated the independent impact of numerical metastatic LN burden on survival. Methods Adult patients with oral cavity squamous cell carcinoma undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004 and 2013. A neck dissection of a minimum of 10 LNs was required. Multivariable models were constructed to assess the association between the number of metastatic LNs and survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Results Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs (HR, 1.34; 95% CI, 1.29 to 1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20 to 1.65; P < .001) and lower neck involvement (HR, 1.16; 95% CI, 1.06 to 1.27; P < .001) also predicted increased mortality. Increasing number of nodes examined was associated with improved survival, plateauing at 35 LNs (HR, 0.98; 95% CI, 0.98 to 0.99; P < .001). In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality. A novel nodal staging system derived by recursive partitioning analysis exhibited greater concordance than the American Joint Committee on Cancer (8th edition) system. Conclusion The number of metastatic nodes is a critical predictor of oral cavity cancer mortality, eclipsing other features such as LN size and contralaterality in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions.

The number of metastatic nodes is a predominant independent factor associated with mortality in hypopharyngeal and laryngeal cancers. Moreover, standard nodal staging factors like LN size and contralaterality have no independent prognostic value when accounting for positive LN number. Deeper integration of quantitative metastatic nodal disease may simplify staging and better triage the need for adjuvant therapy.

Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when considering survival burden. Cancer 2018. © 2018 American Cancer Society.

Differential diagnosis of brain magnetic resonance imaging (MRI) enhancement(s) remains a significant problem, which may be difficult to resolve without biopsy, which can be often dangerous or even impossible. Such MRI enhancement(s) can result from metastasis of primary tumors such as lung or breast, radiation necrosis, infections, or a new primary brain tumor (glioma, meningioma). Neurological symptoms are often the same on initial presentation. To develop a more precise noninvasive MRI diagnostic method, we have engineered a new class of poly(β-L-malic acid) polymeric nanoimaging agents (NIAs). The NIAs carrying attached MRI tracer are able to pass through the blood–brain barrier (BBB) and specifically target cancer cells for efficient imaging. A qualitative/quantitative “MRI virtual biopsy” method is based on a nanoconjugate carrying MRI contrast agent gadolinium-DOTA and antibodies recognizing tumor-specific markers and extravasating through the BBB. In newly developed double tumor xenogeneic mouse models of brain metastasis this noninvasive method allowed differential diagnosis of HER2- and EGFR-expressing brain tumors. After MRI diagnosis, breast and lung cancer brain metastases were successfully treated with similar tumor-targeted nanoconjugates carrying molecular inhibitors of EGFR or HER2 instead of imaging contrast agent. The treatment resulted in a significant increase in animal survival and markedly reduced immunostaining for several cancer stem cell markers. Novel NIAs could be useful for brain diagnostic MRI in the clinic without currently performed brain biopsies. This technology shows promise for differential MRI diagnosis and treatment of brain metastases and other pathologies when biopsies are difficult to perform.

OBJECTIVESpontaneous spinal CSF–venous fistulas are a distinct type of spinal CSF leak recently described in patients with spontaneous intracranial hypotension (SIH). Using digital subtraction myelography (DSM) with the patient in the prone position, the authors have been able to demonstrate such fistulas in about one-fifth of patients with SIH in whom conventional spinal imaging (MRI or CT myelography) showed no evidence for a CSF leak (i.e., the presence of extradural CSF). The authors compared findings of DSM with patients in the lateral decubitus position versus the prone position and now report a significantly increased yield of identifying spinal CSF–venous fistulas with this modification of their imaging protocol.METHODSThe population consisted of 23 patients with SIH who underwent DSM in the lateral decubitus position and 26 patients with SIH who underwent DSM in the prone position. None of the patients had evidence of a CSF leak on conventional spinal imaging.RESULTSA CSF–venous fistula was demonstrated in 17 (74%) of the 23 patients who underwent DSM in the lateral decubitus position compared to 4 (15%) of the 26 patients who underwent DSM in the prone position (p < 0.0001). The mean age of these 16 women and 5 men was 52.5 years (range 36–66 years).CONCLUSIONSAmong SIH patients in whom conventional spinal imaging showed no evidence of a CSF leak, DSM in the lateral decubitus position demonstrated a CSF–venous fistula in about three-fourths of patients compared to only 15% of patients when the DSM was performed in the prone position, an approximately five-fold increase in the detection rate. Spinal CSF–venous fistulas are not rare among patients with SIH.

OBJECTIVE In most patients with spontaneous intracranial hypotension, a spinal CSF leak can be found, but occasionally, no leak can be demonstrated despite extensive spinal imaging. Failure to localize a CSF leak limits treatment options. The authors recently reported the discovery of CSF-venous fistulas in patients with spontaneous intracranial hypotension and now report on the use of digital subtraction myelography in patients with spontaneous intracranial hypotension but no CSF leak identifiable on conventional spinal imaging (i.e., non–digital subtraction myelography). METHODS The patient population consisted of 53 consecutive patients with spontaneous intracranial hypotension who underwent digital subtraction myelography but in whom no spinal CSF leak (i.e., presence of extradural CSF) was identifiable on conventional spinal imaging. RESULTS The mean age of the 33 women and 20 men was 53.4 years (range 29–71 years). A CSF-venous fistula was demonstrated in 10 (19%) of the 53 patients. A CSF-venous fistula was found in 9 (27%) of the 33 women and in 1 (5%) of the 20 men (p = 0.0697). One patient was treated successfully with percutaneous injection of fibrin sealant. Nine patients underwent surgery for the fistula. Surgery resulted in complete resolution of symptoms in 8 patients (follow-up 7–25 months), and in 1 patient, symptoms recurred after 4 months. CONCLUSIONS In this study, the authors found a CSF-venous fistula in approximately one-fifth of the patients with recalcitrant spontaneous intracranial hypotension but no CSF leak identifiable on conventional spinal imaging. The authors suggest that digital subtraction myelography be considered in this patient population.

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