Hasse Ejnell

Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study

BACKGROUNDnExtrahepatic portal vein obstruction can have severe health consequences. Variceal bleeding associated with this disorder causes upper gastrointestinal bleeding, leading to substantial morbidity and mortality. We report the clinical transplantation of a deceased donor iliac vein graft repopulated with recipient autologous stem cells in a patient with extrahepatic portal vein obstruction.nnnMETHODSnA 10 year old girl with extrahepatic portal vein obstruction was admitted to the Sahlgrenska University Hospital in Gothenburg, Sweden, for a bypass procedure between the superior mesenteric vein and the intrahepatic left portal vein (meso Rex bypass). A 9 cm segment of allogeneic donor iliac vein was decellularised and subsequently recellularised with endothelial and smooth muscle cells differentiated from stem cells obtained from the bone marrow of the recipient. This graft was used because the patients umbilical vein was not suitable and other strategies (eg, liver transplantation) require lifelong immunosuppression.nnnFINDINGSnThe graft immediately provided the recipient with a functional blood supply (25-30 cm/s in the portal vein and 40 mL/s in the artery was measured intraoperatively and confirmed with ultrasound). The patient had normal laboratory values for 9 months. However, at 1 year the blood flow was low and, on exploration, the shunt was patent but too narrow due to mechanical obstruction of tissue in the mesocolon. Once the tissue causing the compression was removed the graft dilated. We therefore used a second stem-cell populated vein graft to lengthen the previous graft. After this second operation, the portal pressure was reduced from 20 mm Hg to 13 mm Hg and blood flow was 25-40 cm/s in the portal vein. With restored portal circulation the patient has substantially improved physical and mental function and growth. The patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs.nnnINTERPRETATIONnAn acellularised deceased donor vein graft recellularised with autologous stem cells can be considered for patients in need of vascular vein shunts without the need for immunosuppression.nnnFUNDINGnSwedish Government.

RETRACTED: Replacement of a Tracheal Stenosis with a Tissue-Engineered Human Trachea Using Autologous Stem Cells: A Case Report

Cell-based therapies involving tissue engineering represent interesting and potentially important strategies for the treatment of patients with various disorders. In this study, using a detergent-enzymatic method, we prepared an intact three-dimensional scaffold of an extracellular matrix derived from a human cadaver donor trachea, which we repopulated with autologous stem cells and implanted into a 76-year-old patient with tracheal stenosis including the lower part of the larynx. Although the graft provided the patient with an open airway, a week after the surgery, the mucous membrane of the graft was covered by a 1-2 mm thick fungal infection, which was treated with local and systemic antifungal therapy. The airway lumen was postoperatively controlled by fiber endoscopy and found stable and sufficient. However, after 23 days, the patient died due to cardiac arrest but with a patent, open, and stable tracheal transplant and intact anastomoses. Histopathological results of the transplanted tracheal graft during autopsy showed a squamous but not ciliated epithelium, neovascularization, bundles of α-sma-positive muscle cells, serous glands, and nerve fibers with S-100-positive nerve cells in the submucosa and intact chondrocytes in the cartilage. Our findings suggest that although autologous stem cells-engineered tracheal matrices may represent a tool for clinical tracheal replacement, further preclinical studies are required for generating functional airway grafts and long-term effects of such grafts.

Combined stent insertion and single high‐dose brachytherapy in patients with advanced esophageal cancer – results of a prospective safety study

Previous randomized studies comparing the two commonly used palliative treatments for incurable esophageal cancer, i.e. stent insertion and intraluminal brachytherapy, have revealed the pros and cons of each therapy. While stent treatment offers a more prompt effect, brachytherapy results in more long-lasting relief of dysphagia and a better health-related quality of life (HRQL) in those living longer. This prospective pilot study aimed to explore the feasibility and safety of combining these two regimes and incorporating a single high dose of internal radiation. Patients with newly diagnosed, incurable cancer of the esophagus and dysphagia were eligible for inclusion, and stent insertion followed by a single dose (12 Gy) of brachytherapy was performed as a two-stage procedure. Clinical parameters including HRQL and adverse events were registered at inclusion, and 1, 2, 3, 6, and 12 months later. Twelve patients (nine males) with a median age of 73 years (range 54-85) were included. Stent insertion followed by a single dose of brachytherapy was successfully performed in all but one patient who was treated with stent only. Relief of dysphagia was achieved in the majority of cases (10/11, P < 0.05), but HRQL did not improve except for dysphagia-related items. Only minor adverse events, including chest pain, reflux, and restenosis, were reported. The median survival time after inclusion was 6.6 months. Our conclusion is that the combination of stent insertion and single high-dose brachytherapy seems to be a feasible and safe palliative regime in patients with advanced esophageal cancer. Randomized trials comparing the efficacy of this strategy to stent insertion or brachytherapy alone are warranted.

Surgical treatment of the sleep apnea syndrome reduces associated major depression

Prior small and retrospective studies have indicated that obstructive sleep apnea (OSA) disease-related psychiatric morbidity might be reversed by correcting the sleep-related breathing disorder.To evaluate the effect of surgical intervention (uvulopalatopharyngoplasty, UPPP) on associated psychiatric morbidity we prospectively evaluated a large cohort (n = 53) of OSA patients before and after UPPP.Surgical intervention resulted in a significant reduction of depressive disorder (p < .001) in parallel with improvement of the sleep disorder. Our results show that sleep disturbance and reduced daytime alertness may be at least one of the factors behind depressive symptoms in OSA.

Functional and Radiological Evaluation of Free Jejunal Transplant Reconstructions After Radical Resection of Hypopharyngeal or Proximal Esophageal Cancer

Cancer of the pharyngoesophageal junction (PEJ) is associated with late onset of symptoms, high morbidity, and a dismal prognosis. Radical surgery with pharyngolaryngectomy and reconstruction with a free vascularized jejunal transplant has been increasingly practiced in the treatment of these patients. This strategy is not devoid of challenges, and the present study is aimed at evaluating the long-term functional outcome among patients who have undergone such surgical treatment. Ten patients (mean age 59 years) with a mean follow-up time of 54 months were included. Clinical assessment, health-related quality of life (HRQL) questionnaires, and a standardized radiography examination were used for evaluation. The Karnofsky index ranged from 60 to 90 (mean 82). Global QL scores (EORTC QLQ-C30) had a mean value of 74, and the mean scores for dysphagia-related items of the EORTC QLQ OES-18 questionnaire were within the lower range. Radiographic signs of disturbed bolus transport through the jejunal transplant were found in all patients examined despite the grading of dysphagia from 0 to 1. The Watson dysphagia score varied between 0.5 and 45.0 (mean 16.2). No correlations were found between radiographic findings and the clinical evaluations or the outcomes assessed by the HRQL questionnaires. HRQL was found to be generally good after cancer of the PEJ and jejunal transplant insertion. Most patients reported mild dysphagia. Radiologic signs of disturbed bolus passage were common, but their clinical impact seemed questionable.

Accelerated radiotherapy for advanced laryngeal cancer

The purpose of this study was to evaluate a single institutions outcome for patients with advanced laryngeal cancer treated with accelerated radiotherapy (RT). Fifty-eight patients with advanced laryngeal cancer (T3/T4N0/Nu200a+u200aM0) were treated with curative intent with accelerated RT during the period 1990u200a−u200a1998. Patients received radiotherapy alone or with induction chemotherapy. The 5-year local control (LC) and loco-regional control (LRC) probabilities were both 49% for T3 and 75% for T4 tumors. The 5-year disease-free survival probability was 46% and 68% and overall survival probability was 30% and 39% for T3 and T4 tumors respectively. No significant statistical difference in outcome was found, either between T3 and T4 tumors, or between patients who received induction chemotherapy and those who did not. The treatment results for advanced laryngeal cancer at this institution were comparable to those reported in the literature. The results for T3 and T4 were similar. T4 classification alone should not be an exclusion criterion for larynx preservation. Overall survival was poor, partly because of a high incidence of deaths from intercurrent diseases.

Functional long-term outcome of a free jejunal transplant reconstruction following chemoradiotherapy and radical resection for hypopharyngeal and proximal oesophageal carcinoma

Background/Aims: To evaluate the functional outcome of a reconstruction by a free vascularized jejunal transplant combined with a voice prosthesis after chemoradiotherapy and surgery for proximal oesophageal or hypopharyngeal cancer. Methods: Seven patients (6 men, mean age 52 years, range 28–70) with squamous cell cancer in the proximal oesophagus (n = 6) or the hypopharynx received preoperative chemoradiotherapy (40.8 Gy, cisplatinum and 5-FU) followed by a circumferential pharyngolaryngectomy and resection of the proximal oesophagus. A single-stage reconstruction was carried out with a free jejunal transplant using a microsurgical technique. A tracheojejunal puncture and insertion of a voice prosthesis (Provox I) was performed after 3 months in suitable cases. Results: All operations had a per- and postoperative uneventful course. Five patients were alive after a mean follow-up time of 5 years and 7 months after surgery (range 3 years 4 months to 7 years 10 months), while 2 patients died from metastases within 2 years after surgery. Postoperative examination showed histopathological down-staging in all cases. Relief of dysphagia was achieved in most cases. Good or average speech was recorded in 3 patients. Conclusion: Reconstruction after radical resection for proximal oesophageal and hypopharyngeal cancer can be carried out with low mortality, acceptable morbidity and a promising functional outcome.

The effect of the prone sleeping position on obstructive sleep apnoea

Abstract Conclusions: Prone positioning reveals promising results in improving the apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) in patients with obstructive sleep apnoea (OSA). Objective: To evaluate the effect of the prone position on OSA. Methods: Thirty-two patients with mild to severe OSA were included in the study. This was a two-night study to evaluate the effect of the prone position on OSA; a first night in a normal bed with optional positioning and a second night on a mattress and pillow facilitating prone positioning. Results: A total of 27 patients, 22 males and 5 females, with a mean age of 51 years, 15 patients with positional OSA (POSA) and 12 patients with non-POSA with a total median AHI of 23 (min 5, max 93) completed the study protocol. The median AHI decreased from 23 to 7 (p < 0.001) and the median ODI from 21 to 6 (p < 0.001). The median time spent in the supine position decreased from 142 to <1 min (p < 0.0001) and the median time in the prone position increased from <1 to 330 min (p < 0.0001). In all, 17 of 27 patients (63%) were considered to be responders to prone positioning, 12 of 15 (80%) with POSA and 5 of 12 (42%) with non-POSA. Five patients did not complete the study protocol due to sleep time <4 h.

Autoinflation for treatment of persistent otitis media with effusion in children: a cross-over study with a 12-month follow-up.

OBJECTIVESnThe aims of the present study were to evaluate the efficacy of and compliance with a new device for autoinflation in the treatment of persistent otitis media with effusion (OME) in young children.nnnMETHODSnForty-five children with persistent OME with a bilateral type B or C2 tympanogram for at least three months and history of subjective hearing loss, waiting for grommet surgery, were randomised to a treatment and a control group. Twenty-three children aged between three and eight years started as the treatment group with the new device for autoinflation. Another 22 children, aged between two and eight years were included as controls. After a period of four weeks, a cross-over was performed. Both groups underwent otomicroscopy, tympanometry and audiometry at inclusion and after one and two months for the evaluation of treatment efficiency. The primary outcome measurements were improvement in middle-ear pressure and hearing thresholds at eight weeks. Both groups were then followed up for another 10 months.nnnRESULTSnIn the treatment group, the mean middle-ear pressure for both ears and the mean hearing thresholds for the best ear improved by 166 daPa (p<0.0001) and 6 dB (p<0.0001), respectively after four weeks, while in the control group, non-significant alterations were observed. After the cross-over of the control group to treatment, equivalent improvements in the mean middle-ear pressure and the mean hearing thresholds of 187 daPa (p<0.0001) and 7 dB (p<0.01), respectively were achieved also in this group. After treatment in both groups at eight weeks, four of 45 children were submitted to grommet surgery. During the long-term follow-up another five children were submitted to surgery due to recurrence of disease. All the children managed to perform the manoeuvre and no side-effects were detected.nnnCONCLUSIONnThe device demonstrated efficiency in improving both middle-ear pressure and hearing thresholds in most children after four weeks of treatment. It might therefore be possible to consider this method of autoinflation in children with persistent OME during the watchful waiting period.

A new device for treatment of persistent otitis media with effusion

OBJECTIVESnMost children suffer from otitis media with effusion (OME) before starting school. Insertion of grommets into the eardrum for treatment of OME is one of the most common operations performed in childhood. The efficiency and compliance of treatment with a new non-invasive device was evaluated in children with bilateral OME with disease duration of at least 3 months.nnnMETHODSnA device for autoinflation was developed to enable a combined modified Valsalva and Politzer maneuver. Ten children, aged 3-8 years (mean: 5 years and 2 months) with OME tested the device for estimation of its ability to ventilate the middle ear. Another thirty-one children, with persistent bilateral OME for at least three months, were divided into a treatment and a control group. Twenty-one children (42 ears), aged 2-7 year (mean: 4 years and 6 months), participated as the treatment group and ten patients (20 ears), aged 3-7 years (mean: 4 years and 5 months), were included as controls. Tympanometry and otomicroscopy were performed at inclusion and at the end of the study.nnnRESULTSnIn the treatment group the middle ear pressure was normalized in 52% and improved in 31% of the ears with 7 children (33%) achieving bilateral and 8 (38%) unilateral normalization. In the control group the middle ear pressure was normalized in 15%, improved in 15% and deteriorated in 10% of the ears with one child (10%) achieving bilateral and one child (10%) unilateral normalization. Statistically significant differences (p < 0.001) were observed in the pressure difference and the tympanometry type changes between the treatment and the control group. Otomicroscopic examination revealed that the number of ears judged as OME was reduced by 62% in the treatment group in comparison with 20% in the control group. All children managed to perform the maneuver and no side effects were neither reported nor detected.nnnCONCLUSIONSnThe device was efficient in ventilation of the middle ear with normalization or improvement of the negative middle ear pressure and otomicroscopic findings in young children with persistent OME.