A retrospective matched cohort study evaluating the effects of percutaneous endoscopic gastrostomy feeding tubes on nutritional status and survival in patients with advanced gastroesophageal malignancies undergoing systemic anti-cancer therapy

<div><p>Background</p><p>Many patients with cancer or other systemic illnesses can experience malnutrition. One way to mitigate malnutrition is by insertion of a percutaneous endoscopic gastrostomy feeding tube (PEG tube). The goal of this retrospective matched cohort study is to evaluate if PEG tube placement improved nutritional status and overall survival (OS) in advanced gastroesophageal (GE) cancer patients who are undergoing anti-neoplastic therapy.</p><p>Methods</p><p>GE cancer patients who were treated and evaluated by a nutritionist and had at least 2 nutritionist follow-up visits were identified. Patients with PEG tube were matched to patients that did not undergo PEG placement (non-PEG). Clinical characteristics, GE symptoms reported at nutrition follow-up visits, and OS were recorded.</p><p>Results</p><p>20 PEG and 18 non-PEG cases met criteria for further analyses. After correction for multiple testing, there were no OS differences between PEG and non-PEG, treatment naive and previously treated. However, PEG esophageal carcinoma has statistically significant inferior OS compared with non-PEG esophageal carcinoma. PEG placement did not significantly reduce the proportion of patients with weight loss between the initial nutrition assessment and 12-week follow-up.</p><p>Conclusions</p><p>In this small study, PEG placement had inferior OS outcome for GE esophageal carcinoma, no improvement in OS for other evaluated groups, and did not reduce weight loss between baseline and 12-week follow-up. Unless there is prospective randomized trial that can show superiority of PEG placement in this population, PEG placement in this group cannot be endorsed.</p></div

Symptoms of non-PEG patients (n = 18).

<p>Symptoms of non-PEG patients (n = 18).</p

CONSORT diagram.

<p>CONSORT diagram depicting number of patients evaluated for eligibility and number of patients included in analysis.</p

Clinical characteristics.

<p>Clinical characteristics.</p

Erlotinib fails to inhibit STAT3 activation in EGFR mutant NSCLC cell lines.

<p><b>A–B</b>, Protein lysates from HCC827 (A) and HCC4006 (B) cells treated with DMSO (vehicle) or 2 µM erlotinib for 8 hours were analyzed with antibody microarrays to detect phosphorylation status of receptor tyrosine kinases and key cell signaling proteins. Fluorescent signals for the indicated spots were background subtracted and normalized to positive control spots (indicated with +) on the array. Data is shown as the percentage of average fluorescence for each set of duplicate spots relative to the average fluorescence of ten positive control spots for each array. Data on each graph is ordered according to the number (1–10) indicated on each array. <b>C</b>, HCC827 and HCC4006 cells were treated for one hour with DMSO (con) or a 2-fold escalating dose of erlotinib ranging from 0.25 to 1.0 µM (left-right). The phosphorylation status of EGFR (pEGFR^Y1068), STAT3 (pSTAT3^Y705), AKT (pAKT^S473), ERK (pERK^T202/Y204), and S6 (pS6^S235/S236) was evaluated by immunoblot. Equal amounts of protein (20 µg) were added for each sample. <b>D</b>, HCC4006 cells were treated for two hours with DMSO or 1.0 µM erlotinib, then fixed and stained with antibodies for total STAT3. Cells were counter-stained with DAPI to indicate nuclear accumulation of STAT3. Scale bars, 20 µm.</p

OS comparing PEG vs non-PEG in esophageal carcinoma.

<p>Kaplan-Meier curve depicting the estimated OS for patients with esophageal carcinoma. The line with circles depicts PEG esophageal carcinoma patients, while the line with squares depicts non-PEG esophageal carcinoma patients. P-value is significant after Bonferroni correction.</p

Symptoms of PEG patients (n = 20).

<p>Symptoms of PEG patients (n = 20).</p

OS comparing PEG vs non-PEG in all patients.

<p>Kaplan-Meier curve depicting the estimated OS of all patients. The line with circles depicts PEG patients, while the line with squares depicts non-PEG patients. P-value is not significant after Bonferroni correction.</p

OS comparing PEG vs non-PEG in adenocarcinoma.

<p>Kaplan-Meier curve depicting the estimated OS for patients with adenocarcinoma. The line with circles depicts PEG adenocarcinoma patients, while the line with squares depicts non-PEG adenocarcinoma patients. P-value is not significant after Bonferroni correction.</p

STAT3 phosphorylation is mediated by IL-6 family cytokines in NSCLC cell lines.

<p><b>A</b>, The indicated NSCLC lines were plated at fixed densities and allowed to adhere overnight in serum-containing media. Cells were then treated for 24 hours in serum-free media containing anti-gp130 neutralizing antibody or a control mouse IgG (2.0 µg/mL each). Protein lysates were harvested and the phosphorylation status of STAT3 (pSTAT3^Y705), AKT (pAKT^S473), ERK (pERK^T202/Y204), and S6 (pS6^S235/S236) was evaluated by immunoblot. Equal amounts of protein (30 µg) were added for each sample. <b>B</b>, NSCLC lines were plated at fixed densities and allowed to adhere overnight in serum-containing media. Cells were then serum-starved, and conditioned media was collected at 48 hours. Secreted interleukin-6 (IL-6) levels were measured from the indicated cell lines using a bead-based immunoassay platform. Values shown are averages of duplicate measurements for each sample.</p