Research Spotlight

Armstrong, E. S., J. Reynolds, S. Carroll, C. Sturdivant and M. S. Suterwala (2019). “Comparing videofluoroscopy and endoscopy to assess swallowing in bottle-fed young infants in the neonatal intensive care unit.” J Perinatol Jul 22. [Epub ahead of print].

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OBJECTIVE: To determine the diagnostic accuracy of videofluoroscopy (VFSS) and endoscopy (FEES) in detecting laryngeal penetration and tracheal aspiration in bottle-fed young infants in the NICU. STUDY DESIGN: VFSS and FEES findings of 22 infants were compared to each other and to a composite reference standard in this prospective study. Sensitivity, specificity, positive and negative predictive values were calculated for each assessment. RESULT: Agreement between VFSS and FEES was high (92%) for aspiration and moderate (56%) for penetration, with FEES detecting more instances of penetration. Compared to the composite reference standard, FEES had greater sensitivity and a higher negative predictive value for penetration than VFSS. Because of the low prevalence of aspiration, diagnostic accuracy could not be determined for aspiration for either assessment. CONCLUSION: FEES appears to be more accurate in detecting penetration in this population, and both assessments are valuable tools in a comprehensive feeding and swallowing evaluation.

Yamamura, K., D. Izumi, R. Kandimalla, F. Sonohara, Y. Baba, N. Yoshida, Y. Kodera, B. Hideo and A. Goel (2019). “Intratumoral Fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma.” Clin Cancer Res Jul 29. [Epub ahead of print].

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PURPOSE: Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although Fusobacterium nucleatum (F. nucleatum) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. EXPERIMENTAL DESIGN: The F. nucleatum levels were quantified by qPCR assays in tumor tissues from 551 ESCC patients from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between F. nucleatum burden and recurrence free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECIST), primary tumor metabolic response defined by maximum standardized uptake value (SUVmax) changes in positron emission tomography – computed tomography (PET/CT), and pathological tumor regression grade (TRG). RESULTS: High burden of F. nucleatum in ESCC patients associated with poor RFS in both training (log-rank p=0.02; Hazard Ratio [HR]=1.61; p=0.03) and validation cohorts (log-rank p=0.003; HR=1.96; p=0.004). Importantly, ESCC patients with high levels of F. nucleatum displayed poor chemotherapeutic response for all three evaluation methods: RECIST (p=0.04), SUVmax change in PET/CT (p=0.0004), and TRG (p=0.003). CONCLUSIONS: We conclude that high levels of intratumoral F. nucleatum have a prognostic significance for predicting poor RFS in ESCC patients. More importantly, our data indicates that higher F. nucleatum burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in ESCC patients.

Al-Temimi, M. H., B. Chandrasekaran, J. Agapian, W. R. Peters, Jr. and K. O. Wells (2019). “Robotic versus laparoscopic elective colectomy for left side diverticulitis: a propensity score-matched analysis of the NSQIP database.” Int J Colorectal Dis 34(8): 1385-1392.

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PURPOSE: Robotic surgery might have an advantage over conventional laparoscopy for colonic diverticulitis. We intend to compare both approaches in the elective management of left side diverticulitis. METHODS: The National Surgical Quality Improvement Program (NSQIP) database (2012-2014) was surveyed for patients undergoing elective left/sigmoid colectomy for diverticulitis. Patient demographics, co-morbidities, disease complexity, and intraoperative details were matched on propensity scores derived from logistic regression model. RESULTS: We identified 441 robotic and 6584 laparoscopic cases. Mean age was 56.8 years. Mean BMI was 29.5, and 46.5% of patients were males. Low preoperative albumin (< 3.5 mg/dl, 11.1% vs. 6.8%, p = 0.003), splenectomy (0.45% vs. 0.05%, p = 0.002), and enterotomy repair (1.1% vs. 0.4%, p = 0.029) were higher in the robotic group than the laparoscopic group. Hand assistance (35.8% vs. 42.9%, p = 0.003), splenic flexure takedown (41.5% vs. 49.2%, p = 0.002), and ureteric stent placement (18.6% vs. 23.5%, p = 0.017) were less common in the robotic group than the laparoscopic group. Case-matched analysis showed that robotic surgery was associated with shorter hospital stay (3.89 +/- 2.18 days vs. 4.75 +/- 3.25 days, p < 0.001), lower conversion rate (7.5% vs. 14.3%, p = 0.001), and longer operative time (219.2 +/- 95.6 min vs. 188.8 +/- 82.3 min, p < 0.001) than laparoscopic surgery. Robotic approach was associated with lower overall morbidity in multivariate analysis (OR = 0.72, 95% CI = 0.55-0.96), but not in case-matched analysis (14.4% vs. 19.2%, p = 0.058). CONCLUSIONS: Robotic surgery is associated with shorter hospital stay and lower conversion rate and may offer lower overall morbidity than laparoscopy after elective left side colectomy for diverticulitis. Controlled prospective studies are needed to confirm these findings.

Abu Ahmad, N., M. Raizman, N. Weizmann, B. Wasek, E. Arning, T. Bottiglieri, O. Tirosh and A. M. Troen (2019). “Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.” FASEB 33(8): 9334-9349.

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Methyl-donor deficiency is a risk factor for neurodegenerative diseases. Dietary deficiency of the methyl-donors methionine and choline [methionine-choline-deficient (MCD) diet] is a well-established model of nonalcoholic steatohepatitis (NASH), yet brain metabolism has not been studied in this model. We hypothesized that supplemental betaine would protect both the liver and brain in this model and that any benefit to the brain would be due to improved liver metabolism because betaine is a methyl-donor in liver methylation but is not metabolically active in the brain. We fed male Sprague-Dawley rats a control diet, MCD diet, or betaine-supplemented MCD (MCD+B) diet for 8 wk and collected blood and tissue. As expected, betaine prevented MCD diet-induced NASH. However, contrary to our prediction, it did not appear to do so by stimulating methylation; the MCD+B diet worsened hyperhomocysteinemia and depressed liver methylation potential 8-fold compared with the MCD diet. Instead, it significantly increased the expression of genes involved in beta-oxidation: fibroblast growth factor 21 and peroxisome proliferator-activated receptor alpha. In contrast to that of the liver, brain methylation potential was unaffected by diet. Nevertheless, several phospholipid (PL) subclasses involved in stabilizing brain membranes were decreased by the MCD diet, and these improved modestly with betaine. The protective effect of betaine is likely due to the stimulation of beta-oxidation in liver and the effects on PL metabolism in brain.-Abu Ahmad, N., Raizman, M., Weizmann, N., Wasek, B., Arning, E., Bottiglieri, T., Tirosh, O., Troen, A. M. Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.

Abramson, V. G., M. Oliveira, A. Cervantes, H. Wildiers, M. R. Patel, T. M. Bauer, P. L. Bedard, C. Becerra, S. Richey, M. C. Wei, E. Reyner, J. Bond, N. Cui, T. R. Wilson, H. M. Moore, C. Saura and I. E. Krop (2019). “A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer.” Breast Cancer Res Treat Jul 31. [Epub ahead of print].

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PURPOSE: This open-label, phase Ib, dose-escalation, and dose-expansion study (NCT01862081) evaluated taselisib with a taxane in locally advanced or metastatic breast cancer (BC) and/or non-small cell lung cancer (NSCLC). METHODS: Patients received taselisib (2-6 mg tablet or 3-6 mg capsule) plus docetaxel or paclitaxel. Primary endpoints were safety, dose-limiting toxicities, maximum tolerated dose, and identification of a recommended phase II dose. Secondary endpoints included pharmacokinetics and antitumor activity assessment. RESULTS: Eighty patients (BC: 72; NSCLC: 7; BC/NSCLC: 1) were enrolled (docetaxel-receiving arms: 21; paclitaxel-receiving arms: 59). Grade >/= 3 adverse events (AEs), serious AEs, and AEs leading to death were reported in 90.5%, 42.9%, and 14.3% of patients, respectively (docetaxel-receiving arms), and 78.9%, 40.4%, and 3.5% of patients, respectively (paclitaxel-receiving arms). Eight patients experienced dose-limiting toxicities. The maximum tolerated dose was exceeded with 3 mg taselisib (capsule) for 21 consecutive days plus 75 mg/m(2) docetaxel and not exceeded with 6 mg taselisib (tablet) for 5 days on/2 days off plus 80 mg/m(2) paclitaxel. Objective response rates and clinical benefit rates were 35.0% and 45.0%, respectively (docetaxel-receiving arms), and 20.4% and 27.8%, respectively (paclitaxel-receiving arms). Exposure for paclitaxel or docetaxel plus taselisib was consistent with the single agents. CONCLUSIONS: Taselisib in combination with a taxane has a challenging safety profile. Despite evidence of antitumor activity, the benefit-risk profile was deemed not advantageous. Further development is not planned.