Clinical application of decellularized and lyophilized human amnion/chorion membrane grafts for closing post‐laryngectomy pharyngocutaneous fistulas

Background and Objectives

Squamous cell carcinoma is the most common pathological type among the cancers of the larynx. Standard treatment for squamous cell carcinoma of the larynx is the combination of chemotherapy, radiotherapy, and laryngectomy. Pharyngocutaneous fistula is a common complication of laryngectomy. We hypothesized that decellularized and lyophilized human amnion/chorion membrane can be an effective, non‐invasive method of treating pharyngocutaneous fistula.

Methods

A total of 67 patients with laryngeal squamous cell carcinoma were retrospectively analyzed after treatment in a prospective trial. After preoperative chemotherapy, radiotherapy, and total or extended laryngectomy, primary wound healing occurred in 42 (62.7%) patients. Pharyngocutaneous fistula developed in 8 (11.9%) patients. Decellularized and lyophilized human amnion/chorion membrane grafts were used to reconstruct the fistulas.

Results

The average time for the full healing of the wound in all patients after transplantation of these grafts was 18 days.

Conclusion

The advantages of using these grafts over other existing methods of pharyngocutaneous fistula treatment are that they are non‐invasive, prevent donor morbidity, and enable management of the wound without using classical wound gauze. J. Surg. Oncol. 2016;113:538–543. © 2016 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.     

Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study

OBJECTIVE: To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. METHODS: We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA. RESULTS: We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]). CONCLUSION: RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.     

Pilot Study Evaluating Regulatory T Cell–Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model

The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1‐ethyl‐3‐(3′‐dimethylaminopropyl)‐carbodiimide (ECDI)‐treated donor lymphoid cell infusion (ECDI‐DLI) with thymoglobulin, anti‐interleukin‐6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor‐specific T cell hyporesponsiveness and a transient absence of donor‐specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.     

High frequency of K-ras mutations in normal appearing lung tissues and sputum of patients with lung cancer

To evaluate the possible use of mutant ras as a biomarker for lung cancer, we have analyzed “normal appearing” lung tissue, lung tumor, lung metastases and sputum samples from patients with non-small cell lung cancer (NSCLC). As a control, we used lung tissue and sputum samples from patients without oncological diseases or lung disorders. Our analyses were performed with the aid of enriched PCR (EPCR), a method which enables detection of ras mutation even if present at low incidence. EPCR identified K-ras codon 12 mutations in 10% of lung tissues obtained from patients with no lung diseases, whereas the same mutation was detected in 60% of samples of normal appearing lung tissues obtained from patients with NSCLC, 62% of NSCLC tumors and 80% of metastases. Analysis of sputum samples of patients with NSCLC identified 47% to harbor mutant ras allele, whereas 12.5% of controls diagnosed with non-oncological lung diseases carried this mutation. Most of these mutations were detected with the aid of EPCR only, indicating that a minority of cells in a given sample harbor this mutation. The ability to detect K-ras codon 12 mutation in 60% of lung tissue samples and in 47% of sputum samples taken from patients with lung cancer (as compared with 10% and 12.5% of respective controls) points to the potential use of ras mutation as a biomarker for exposure and possible identification of patients who may be at a higher risk of developing lung cancer. © 1995 Wiley-Liss, Inc.     

Gene transfer via reversible plasmid condensation with cysteine-flanked,internally spaced arginine-rich peptides

Nonviral gene transfer offers biosafety, stability, and expense advantages over viruses; however, it has suffered from poor efficiency. Because arginine-rich peptides facilitate uptake of macromolecules such as proteins, liposomes, and iron nanoparticles, we explored their potential in enhancing plasmid DNA delivery. In their unmodified form, known protein transduction sequences, including hepta-arginine and Tat(47-57), failed to support effective gene delivery. However, by flanking a core of consecutive arginines with amino- and carboxy-terminal cysteines in vitro gene transfer was observed. Furthermore, interspersing arginines with glycine and histidine residues achieved reversible plasmid condensation and dramatically increased transfection levels in a variety of cell types. Unlike most available cationic homopolymers that function only in vitro, these new peptides also increased gene expression in both murine and human tissue in vivo. Thus, cysteine-flanked, internally spaced arginine-rich (CFIS-R) peptides represent a new approach to efficient nonviral plasmid delivery using rationally designed protein transduction domains.     

Is Cerebral Microembolism in Mechanical Prosthetic Heart Valves Clinically Relevant?

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) are frequently detected by transcranial Doppler (TCD) ultrasound in patients with mechanical prosthetic heart valves (PHVs), but published data about their clinical relevance are controversial. This study was undertaken to determine the clinical relevance of HITS in patients with mechanical PHVs. METHODS: The authors prospectively studied patients with mechanical PHVs using TCD monitoring for microemboli detection with and without O2 inhalation. The cognitive testing of patients included the Mini-Mental State Examination, the Dementia Rating Scale, and MicroCog. RESULTS: The authors studied 36 patients (20 women, aged 58 +/- 13 years). HITS were detected in 72% of patients, with a nonsignificant increase of HITS rate in the aortic valve group (P = .07). There was no significant difference in HITS rate between asymptomatic and symptomatic patients. In a multiple linear regression model, HITS rate was predicted only by younger age (P = .024). No correlation was found between HITS rate and the cognitive performance of patients. There was a significant decrease in HITS rate after 100% O2 inhalation compared to baseline levels (32.8 +/- 40.2 vs 6.1 +/- 11.3, P = .011). Subgroup analysis in asymptomatic patients confirmed this finding (P = .017), but in symptomatic patients, decreased HITS rate was not statistically significant (P = .18). CONCLUSION: Only age was a significant predictor of HITS in patients with mechanical PHVs. The lack of association between HITS, clinical symptoms, and cognitive functioning suggests that most of these signals represent harmless epiphenomena, and only HITS detected after O2 inhalation have any clinical relevance.     

Laparoscopic Nissen fundoplication is a good option in patients with abnormal esophageal motility

Background

Patients with gastroesophageal reflux disease (GERD) and abnormal esophageal motility are the most controversial subgroup of surgically treated patients because of potentially increased risk of postoperative dysphagia. Our study aim was to determine if Nissen fundoplication is associated with increased postoperative dysphagia in patients with ineffective esophageal motility.

Methods

Medical records of all adult (>18 years old) patients who underwent laparoscopic Nissen fundoplication for GERD over 8 years were reviewed retrospectively. Of the 151 patients, 28 (group A) met manometric criteria for abnormal esophageal motility (<30 mmHg mean contractile pressure or <80% peristalsis), whereas 63 (group B) had normal esophageal function. Sixty patients had no manometric data and were therefore excluded from analysis. Follow-up time ranged from 1 month to 5 years. Outcomes (postoperative dysphagia, recurrence of GERD symptoms, free of medications) were compared between groups.

Results

Group A had higher age and American Society of Anesthesiologists (ASA) score (p = 0.016 and 0.020), but this did not correlate with outcome. Two patients (7.1%) in group A and three patients (5.3%) in group B had postoperative dysphagia. When adjusted for follow-up time, there was no significant difference between the groups (p = 0.94). Group B had more cases of recurrent heartburn (10.7% versus 3.6%, p = 0.039), and more patients in this group were back on medications (21.4% versus 7.1%, p < 0.05)

Conclusions

This retrospective study found equally low rates of dysphagia following Nissen fundoplication regardless of baseline esophageal motility. Preoperative esophageal dysmotility therefore does not seem to be a contraindication for laparoscopic Nissen fundoplication.