Insulin Action in the Brain: Roles in Energy and Glucose Homeostasis

Summary

A growing body of evidence from research in rodents and humans has identified insulin as an important neuoregulatory peptide in the brain, where it coordinates diverse aspects of energy balance and peripheral glucose homeostasis. This review discusses where and how insulin interacts within the brain and evaluates the physiological and pathophysiological consequences of central insulin signalling in metabolism, obesity and type 2 diabetes.

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Transoral robotic retropharyngeal node dissection in oropharyngeal squamous cell carcinoma: Patterns of metastasis and functional outcomes

Abstract

Background

Assessment of the retropharyngeal lymph nodes is essential in the treatment for oropharyngeal squamous cell carcinoma (SCC). Transoral robotic retropharyngeal lymph node dissection (RPLND) may provide valuable staging information and guide selection of adjuvant therapy in a transoral robotic surgery (TORS) treatment paradigm.

Methods

Outcomes were compared between 30 patients with oropharyngeal SCC with tonsillar primaries undergoing RPLND and 37 stage-matched cases without RPLND.

Results

Retropharyngeal metastasis was confirmed in 6 patients undergoing RPLND. Compared with 37 stage-matched controls, there were no differences in length of stay, length of feeding tube dependence, net change in perioperative weight, or rates of hemorrhage and postoperative complications. RPLND altered adjuvant treatment recommendations in 1 of 30 patients.

Conclusion

RPLND is technically feasible by a purely transoral robotic approach. Its performance is not associated with worse swallowing outcomes or rates of complication. In select patients, RPLND may provide valuable staging information and guide the selection of adjuvant therapy.

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Transoral robotic retropharyngeal node dissection in oropharyngeal squamous cell carcinoma: Patterns of metastasis and functional outcomes

Abstract

Background

Assessment of the retropharyngeal lymph nodes is essential in the treatment for oropharyngeal squamous cell carcinoma (SCC). Transoral robotic retropharyngeal lymph node dissection (RPLND) may provide valuable staging information and guide selection of adjuvant therapy in a transoral robotic surgery (TORS) treatment paradigm.

Methods

Outcomes were compared between 30 patients with oropharyngeal SCC with tonsillar primaries undergoing RPLND and 37 stage-matched cases without RPLND.

Results

Retropharyngeal metastasis was confirmed in 6 patients undergoing RPLND. Compared with 37 stage-matched controls, there were no differences in length of stay, length of feeding tube dependence, net change in perioperative weight, or rates of hemorrhage and postoperative complications. RPLND altered adjuvant treatment recommendations in 1 of 30 patients.

Conclusion

RPLND is technically feasible by a purely transoral robotic approach. Its performance is not associated with worse swallowing outcomes or rates of complication. In select patients, RPLND may provide valuable staging information and guide the selection of adjuvant therapy.

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Eccrine Chromhidrosis in an Adolescent with Sickle Cell Disease

Abstract

Eccrine chromhidrosis can occur secondary to hyperbilirubinemia. We report an adolescent with sickle cell disease who presented with eccrine chromhidrosis on his palmar and plantar surfaces. He had extremely high levels of conjugated bilirubin but no fever. This is the youngest known reported patient with eccrine chromhidrosis and the first in a patient with sickle cell disease.

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Acanthosis Nigricans and Its Response to Metformin

Abstract

Acanthosis nigricans (AN) is the most common cutaneous manifestation of insulin resistance (IR) and is commonly seen in non-Caucasian populations. Variable benefits of metformin in the treatment of AN have been reported in the literature. We report an adolescent Caucasian boy with IR and extensive AN who showed complete resolution of AN after 2 years of metformin, despite persistence of IR.

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Pulsed-Dye Laser Treatment of Port-Wine Stains in Children: Useful Tips to Avoid General Anesthesia

Abstract

Pulsed dye laser (PDL) treatment of port-wine stains (PWSs) in children is a common procedure performed in most laser units. Pain assessment in our younger patients is a major concern, especially in those with extensive PWSs. The use of general anesthesia (GA) results in pain-free treatment, but its effects on the developing brain are far from totally understood. Thus we propose some tips that avoid the use of GA in most of our young patients, including the use of topical anesthetics and cooling systems, large laser spot size and high frequencies, early and frequent treatment with parents present, and the "introduction" and "pressure" techniques, among others.

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Next generation sequencing of progressive colorectal liver metastases after portal vein embolization

Abstract

Portal vein embolization (PVE) can be required to stimulate liver regeneration before hepatectomy for colorectal liver metastasis (CRCLM), however PVE may also trigger CRCLM progression in patients initially exhibiting chemotherapy response. Using RNA-seq, we aimed to determine the molecular networks involved in metastatic progression in this context. A prospective study including all CRCLM patients undergoing PVE prior to hepatectomy was conducted. Paired biopsies of metastatic lesions were obtained prior to and after PVE and total RNA was isolated and used to prepare Illumina rRNA-depleted TruSeq stranded cDNA libraries for HiSeq 100 bp paired-end sequencing. Patients were classified with progression of disease (PD_PVE) or stable disease (SD_PVE) post-PVE using 3D-CT tumor volumetric analysis. Results: Twenty patients were included, 13 (65.0%) in the PD_PVE group (median 58.0% (18.6–234.3) increase in tumor volume) and 7 (35.0%) in the SD_PVE group exhibiting continuous chemotherapy response (median −14.3% (−40.8 to −2.8) decrease in tumor volume) (p < 0.0001). Our results showed that progressive CRCLM after PVE undergo gene expression changes that indicate activation of core cancer pathways (IL-17 (p = 5.94 × 10⁻⁰³), PI3K (p = 8.71 × 10⁻⁰³), IL6 and IGF-1 signaling pathways), consistent with changes driven by cytokines and growth factors. Differential expression analysis in a paired model of progression (EdgeR, DeSeq) identified significantly dysregulated genes in the PD_PVE group (FOS, FOSB, RAB20, IRS2). Conclusion: Differentially expressed genes and pathways with known links to cancer and metastasis were identified post-PVE in patients with disease progression. Highlighting these molecular changes is a crucial first step towards development of targeted therapeutic strategies that may mitigate the effects of PVE on tumor growth.

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