Suspected malignant hyperthermia in a child with laminin alpha2 (merosin) deficiency in the absence of a triggering agent

Malignant hyperthermia (MH) is an inherited disorder of the skeletal muscles that can be triggered by many anesthetic agents. MH has different presentations and manifestations that makes it difficult to diagnose. Patients with laminin alpha2 deficiency have never been reported to be susceptible to MH. We present a suspected MH episode in the absence of classic triggering agents in a 7-year-old boy with laminin alpha2 (merosin) deficiency and congenital muscular dystrophy. The episode was diagnosed using the MH clinical grading scale and responded well to prompt management with dantrolene. We conclude that patients with laminin alpha2 deficiency may be susceptible to MH, and early suspicion and rapid treatment is vital in the management of MH. Anesthesiologists should be prepared to treat MH in susceptible patients even in the absence of a classical triggering agent.     

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.     

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.     

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.     

Differential susceptibility of renal carcinoma cell lines to tumor suppression by exogenous Fhit expression

Hemizygous deletions of the fragile histidine triad (FHIT) gene at human chromosome band 3p14.2 and down-regulation of its gene product are found in the majority of renal cell carcinomas (RCCs). Functional tumor suppressive activity of Fhit in renal cancer cells previously was observed in RCC cell line RC48, which lacks endogenous Fhit expression. To further investigate the potential role of FHIT as a tumor suppressor gene in RCC, we transfected FHIT cDNA expression constructs into RCC cell lines RCC-1 and SN12C, which show low-level expression of endogenous Fhit and reveal an intact von Hippel-Lindau (VHL) gene. Stable transfectants of both cell lines showed no alterations of cell morphology, proliferation kinetics, or cell cycle parameters in vitro. The FHIT gene transfer rate, however, was significantly lower in RCC-1 cells compared with SN12C cells, suggesting a selection against exogenous Fhit expression. In addition, in nude mouse assays, a significant delay of tumor formation was observed for FHIT-transfected RCC-1 cell lines, with outgrowing tumors demonstrating loss of Fhit expression in the majority of cells. In contrast, tumorigenicity of FHIT-transfected SN12C cell clones was not suppressed, despite stable transgene expression. In conclusion, our results demonstrate a selective tumor suppressive activity of Fhit in RCC cells in vivo and suggest that the susceptibility to suppression is not restricted to cancer cells with complete loss of Fhit expression.     

Increasing participation in cervical screening by targeting long-term nonattenders: Randomized health services study

High screening participation in the population is essential for optimal prevention of cervical cancer. Offering a high-risk human papillomavirus (HPV) self-test has previously been shown to increase participation. In this randomized health services study, we evaluated four strategies with regard to participation. Women who had not attended organized cervical screening in 10 years were eligible for inclusion. This group comprised 16,437 out of 413,487 resident women ages 33–60 (<4% of the screening target group). Among these 16,437 long-term nonattenders, 8,000 women were randomized to either (i) a HPV self-sampling kit sent directly; (ii) an invitation to order a HPV self-sampling kit using a new open source eHealth web application; (iii) an invitation to call a coordinating midwife with questions and concerns; or (iv) the standard annual renewed invitation letter with prebooked appointment time (routine practice). Overall participation, by arm, was (i) 18.7%; (ii) 10.7%; (iii) 1.9%; and (iv) 1.7%. The relative risk of participation in Arm 1 was 11.0 (95% CI 7.8–15.5), 6.3 (95% CI 4.4–8.9) in Arm 2 and 1.1 (95% CI 0.7–1.7) in Arm 3, compared to Arm 4. High-risk HPV prevalence among women who returned kits in study Arms 1 and 2 was 12.2%. In total, 63 women were directly referred to colposcopy from Arms 1 and 2; of which, 43 (68.3%) attended and 17 had a high-grade cervical lesion (CIN2+) in histology (39.5%). Targeting long-term nonattending women with sending or offering the opportunity to order self-sampling kits further increased the participation in an organized screening program.     

Stent placement for benign colonic stenosis: case report,review of the literature,and animal pilot data

BACKGROUND: Permanent metal stent placement for malignant intestinal obstruction has been proven to be efficient. Temporary stents for benign conditions of the colon and rectum are less studied. This is a case study, review of the literature, and observation from an animal model on placement of stents in the colorectum for benign disease. MATERIALS AND METHODS: A 55-year-old man presented with recurrent obstructions from a benign stricture of the distal sigmoid colon. After failed balloon dilations, a polyester coated stent was placed. The purpose of the stent was to improve symptoms and avoid surgery. The stent was expelled after 5 days. We conducted a literature review of stents placed for benign colorectal strictures and an animal study to evaluate stent migration. RESULTS: In the literature, there were 53 reports of uncovered metal stents, four covered metal stents, and six polyester stents. Patency rates were 71%, and migration rate was 43%. Migration occurred earlier with polyester stents (mean = 8 days) versus covered (32 days) or uncovered metal stents (112 days). Severe complications were seen in 23% of patients. Four 45-kg pigs underwent rectosigmoid transection with a 21-mm anastomosis and endoscopic placement of a Polyflex stent. Two stents were secured with suture. Stents without fixation were expelled within 24 h of surgery. Stents with fixation were expelled between postoperative days 2 and 14. CONCLUSION: Stents for the treatment of benign colorectal strictures are safe, with comparable patency rates between stent types. Metal stents can cause severe complications. In a pig model, covered polyester stents tend to migrate early even with fixation. Further investigation needs to focus on new stent designs and/or better fixation.     

Petrous Carotid Artery’s In Situ Bypass: Anatomic Study

The purpose of our study was to reveal the possibility of cervical-to-petrous carotid artery in situ bypass with maximum preservation of cranial nerves. Four human cadavers prepared in formalin were investigated. Eight surgical approaches were used (bilateral exposure on each cadaver). The skin incision started from the level of the temporomandibular joint. The VII, IX, X, and XII cranial nerves, starting from the stylomastoid angle, were maximally preserved. Resection of the styloid process, subluxation of the mandibular joint, and milling of tympanic bone revealed the petrous carotid artery. Exposure of the carotid bifurcation was performed with a mini-skin incision. After dividing the petrous internal carotid artery (ICA) and the cervical ICA, the cervical ICA was dilated using a Fogarty catheter to simulate aneurysmal dilatation. The patient’s saphenous vein after stripping was utilized for the bypass. The vein was passed into the lumen of the dilated cervical ICA, and a cervical-to-petrous carotid bypass was performed. In each case, the described technique made it possible to expose the intrapetrous carotid artery adequately. In two cases it was impossible to make a luxation, and therefore the mandibular branch was resected. The vertical segment’s mean length was 12 mm (range 10–15 mm). In all cases, the VII, IX, X, and XII cranial nerves were preserved maximally. The main points of the approach are luxation of the mandibular articulation and milling of the tympanic bone. Our study in cadavers suggests the possibility of petrous carotid artery bypass without exposing the cervical ICA.     

Prospective randomized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery

BACKGROUND: Recent publications demonstrating the safety and advantages of N2O for pneumoperitoneum (PP) prompted us to reconsider N2O as an agent for PP in general surgical laparoscopy. The purpose of this prospective, double-blind, randomized clinical trial was to determine whether N2O PP has any benefits over CO2 PP. STUDY DESIGN: One hundred three patients received N2O (group I, n = 52) or CO2 (group II, n = 51) PP for elective laparoscopic surgery. Heart rate, mean arterial blood pressure, end-tidal CO2, minute ventilation, and O2 saturation were recorded before PP, during PP, and in the recovery room. Postoperative pain medication use was recorded. Pain was assessed by means of visual analog scale (VAS) at postoperative hours 2 and 4, and on day 1. RESULTS: There were no differences between groups I and II in patient age, gender, weight, anesthesia risk (American Society of Anesthesiologists Score > 2), operative time, duration of PP, or length of hospital stay. Mean end-tidal CO2 increase under anesthesia was greater in group II than group I (3.0 versus 0.5 mmHg, p < 0.001) despite a greater mean intraoperative increase in minute ventilation in group II than group I (0.7 versus -0.2 L/min p < 0.001). The patients who had N2O PP had less pain 2 hours postoperatively (VAS: 4.9 versus 5.7, p <0.05), 4 hours postoperatively (VAS: 3.3 versus 5.1, p < 0.01), and 1 day postoperatively (VAS: 1.7 versus 3.5, p < 0.01) than patients who had CO2 PP. Postoperative narcotic or ketorolac use was not statistically different between groups. There were no adverse events related to either N2O or CO2 pneumoperitoneum. CONCLUSIONS: These results suggest that the use of N2O PP has sufficient advantages over CO2 that it should be considered as the standard agent for therapeutic PP.