SummaryThe transmembrane protein, STRA6, functions as a vitamin A transporter and a cytokine receptor when activated by vitamin A-bound serum retinol binding protein 4 (RBP4). STRA6 activation transduces a JAK2-STAT3 signaling cascade and promotes tumorigenesis in a xenograft mouse model of colon cancer. We show here that RBP4 and STRA6 expression is associated with poor oncologic prognosis. Downregulating STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. Furthermore, we show that high-fat diet (HFD) increases LGR5 expression and promotes tumor growth in a xenograft model independent of obesity. HFD increased STRA6 levels, and downregulation of STRA6 delays and impairs tumor initiation, tumor growth, and expression of stemness markers. Together, these data demonstrate a key role of STRA6 and RBP4 in the maintenance of colon cancer self-renewal and that this pathway is an important link through which consumption of HFD contributes to colon carcinogenesis.

ALK overexpression can be identified in up to 70% of GBMs and does not correlate with underlying gene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study.

A 24 year-old white right handed woman with an otherwise unremarkable medical and family history was admitted with vertigo, hiccups, intractable vomiting, gait unsteadiness and oscillopsia that developed gradually over 9 months.Although initially relapsing and remitting, her manifestations became persistent approximately one month prior to her admission. Neurological examination revealed periodic alternating nystagmus, gait ataxia and bilaterally brisk tendon reflexes in upper and lower extremities and a right extensor plantar reflex. On admission brain MRI there were several lesions with increased T2/FLAIR ( Fig. 1BCD) and low T1 signal including a space-occupying lesion in the left half of the pons, extending into the left middle cerebellar peduncle, the medulla and the lower mesencephalic tectum (Fig. 1A). Lesions did not exhibit gadolinium enhancement ( Fig. 1A) but showed restricted diffusion in diffusion-weighted sequences (Fig. 1E). Spinal cord MRI was normal. CSF analysis on admission and two months later showed normal cell counts and glucose levels, increased protein (83mg/dL and 90mg/dL, respectively), normal IgG index and no oligoclonal bands. CSF flow cytometric analysis was within normal values and CSF cytology was negative for neoplastic cells in both occasions. Full blood counts, biochemistry, serum LDH, thyroid studies, coagulation profiles, ESR, CRP, autoimmune antibody screening including anti-AQP IV antibodies, plasma folate and B12 vitamin levels, plasma protein immunoelectrophoresis, complement levels, urine analysis and serology for hepatitis and HIV were normal. Bone marrow biopsy and contrast-enhanced whole body CT, upper and lower endoscopy and abdominal ultrasonography were unremarkable. Fundoscopy and slit-lamp examination were also unremarkable. Upon magnetic resonance spectroscopy findings suggestive of tumefactive demyelinating lesions, the patient was treated with two monthly courses of mitoxantrone with no apparent clinical benefit and expansion of lesions on MRI, yet still without gadolinium enhancement. A month after the second course of mitoxantrone she developed dysphagia, voice hoarseness and cachexia. Neurological examination revealed left abducens palsy, pathological left-sided cerebellar tests in addition to previous findings and posterior laryngoscopy showed left vocal cord paresis. A new CSF analysis revealed a raised protein level (130mg/dL) with normal cell counts and glucose. CSF cytology, oligoclonal bands were negative and flow cytometric analysis was within normal ranges. A new brain MRI indicated enlargement of pre-existing lesions with peripheral gadolinium enhancement of the brainstem space-occupying lesion (Fig. 1F). Stereotactic biopsy of the brainstem lesion was performed.

Distal epithelioid sarcoma is a rare and slowly growing tumor that usually develops in the upper extremities of young adults. Neoplastic cells have both spindle and epithelioid appearance and are characterized by the loss of the nuclear protein SMARCB1/INI1. We present the case of a distal epithelioid sarcoma arising in the thumb of a 14-year-old girl, which immunohistochemically was characterized by the loss of SMARCB1/INI1 protein as well as the expression of podoplanin (D2-40), TLE1, Glut1, and Ca 125; plus, we highlight the differential diagnosis of epithelioid sarcoma from its histological mimics.

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Objective: To determine the optimal perioperative care strategy for hepatectomy patients by measuring patient reported outcomes. Methods: One-hundred seventy-four patients with liver malignancy were administered a validated patient reported outcomes tool before and after hepatectomy to assess symptom scores (core and GI-specific symptoms) and life interference ratings. The median age was 56 years (range: 22e98 yrs), 54% were male, and 94% were ASA score 3. 51 patients (29%) had 4 liver segments resected and 51 patients (29%) were operated with a minimally-invasive approach. Anesthetic approaches included epidural (94 pts, 54%), TAP block (63 pts, 36%), non-narcotic intraoperative IV analgesia (36 pts, 21%) and enhanced recovery protocol (ERP, 123 pts, 71%), consisting of nonnarcotic oral analgesia, early feeding and early ambulation. Results: The median length of hospital stay was 5 days (range: 1e19 days), with 11 patients (6%) experiencing major complications, including 1 patient (0.6%) with liver failure and 5 patients (3%) with postoperative bile leak. Within 90 days of surgery, 3 patients required reoperation, 3 were readmitted and there were no mortalities. In multivariate analysis, return to baseline for core symptoms was associated with LOS <6 days (OR: 2.78, p = 0.004) and absence of complications (OR: 2.63, p = 0.007), return of GI function was only associated with smaller magnitude of surgery (OR: 5.1, p = 0.001), and return to overall functional status was associated with absence of complications (OR: 2.32, p = 0.03) and ERP-directed care (OR: 2.29, p = 0.04). Conclusion: Independent of surgical approach and perioperative anesthetic technique, patients report that the strongest predictor of rapid return to normal function after hepatectomy is management on an enhanced recovery protocol.

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Objective: Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on longterm prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the study was to define the association of primary tumor location on prognosis of patients undergoing hepatic resection for NELM. Methods: Between 1990 and -2014, 421patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified by location of the primary tumor (PNETvs non-PNET). A propensity score matched analysis was utilized to assess the impact of primary tumor location on long-term survival. Results: Overall, 197(46.8%) patients had NELM from a PNET primary while 224 (53.2% had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). The extent of liver involvement was comparable among PNET vs. non-PNET patients (>50%: 70.6% vs. 76.3%, respectively; P = 0.19). Patients with PNET and NELM were, however, more likely to have extrahepatic disease (5.6%) compared with non-PNET patients (12.9%) (P = 0.01). At the time of surgery, most patients underwent a minor resection (<3 segments) (PNET, 63.8% vs. non-PNET, 60.3%; P = 0.46). On final pathology, patients with a primary PNET were more likely to have NELM characterized as moderate-or poorly-differentiated (P = 0.005). Post-operatively, patients with a history of primary PNET were less likely to receive somatostatin-analog/targeted adjuvant therapy than non-PNET patients (15.2% vs. 29.9%, respectively; P < 0.001). Patients with PNET + NELM had a worse disease-free (DFS) and overall survival (OS) compared with patients who had non-PNET + NELM