Stem Cell Therapy: A Compassionate Use Program in Perianal Fistula.

AIM: To report our experience in a compassionate use program for complex perianal fistula. METHODS: Under controlled circumstances and approved by European and Spanish laws, a compassionate use program allows the use of stem cell therapy for patients with nonhealing diseases, mostly complex fistula-in-ano, who do not meet criteria to be included in a clinical trial. Candidates had previously undergone multiple surgical interventions that had failed. The intervention consisted of surgery (with closure of the internal opening or a surgical flap performance), followed by stem cell injection. Three types of cells were used for implant: stromal vascular fraction, autologous expanded adipose-derived, or allogenic adipose-derived stem cells. Healing was evaluated at 6th month follow-up. Outcome was classified as partial response or healing. Relapse was evaluated 1 year later. Maximum follow-up period was 48 months. RESULTS: 45 patients (24 male) were included; the mean age was 45 years, which ranged from 24 to 69 years. Since some of them received repeated doses, 52 cases were considered (42 fistula-in-ano, 7 rectovaginal fistulas, 1 urethrorectal fistula, 1 sacral fistula, and 1 hidradenitis suppurativa). Regarding fistula-in-ano, there were 18 Crohn's-associated and 24 cryptoglandular. 49 cases (94.2%) showed partial response starting 6.5 weeks of follow-up. 24 cases (46.2%) healed in a mean time of 5.5 months. A year later, all patients cured remained healed. No adverse effects related to stem cell therapy were reported. CONCLUSION: Stem cells are safe and useful for treating anal fistulae. Healing can be achieved in severe cases.

A stepwise approach based on a rational use of components separation and double mesh prosthesis for incisional hernia repair.

PURPOSE: We aimed to evaluate the results of a protocol for a tension-free reconstruction of the abdominal wall in midline incisional hernia repair, based on the rational association of components separation and prosthesis, independently of the hernia size. METHODS: A total of 100 consecutive patients with midline incisional hernias were prospectively included in the study. Three groups according to the transverse diameter of the defect [group A (<4 cm, N = 18), group B (4-10 cm, N = 59), and group C (>10 cm, N = 23)] were identified. RESULTS: Components separation was necessary in 54% of the patients: 16.7% (3/18) in group A, 59.3% (35/59) in group B, and 69.6% (16/23) in group C. Complete tension-free reconstruction was achieved in 87% of the patients: 94.4% (17/18) in group A, 91.5% (54/59) in group B, and 69.6% (16/23) in group C. Overall morbidity rate was 21% (21/100) [group A 16.7% (3/18), group B 22% (13/59), and group C 21.7% (5/23)]. Hospital length of stay was 3.7 ± 3.3 days (group A 1.83 ± 1.43 days, group B 3.05 ± 2.11 days, and group C 6.91 ± 4.45 days). Median follow-up was 25 months (interquartile range 12.25-55.25) with overall recurrence of 2%. CONCLUSION: A tension-free abdominal wall reconstruction can be achieved in most cases of small and large midline incisional hernia repair, by a stepwise approach based on a rational association of components separation and double mesh prosthesis, with a low morbidity and recurrence rates.

Identification of Poor-outcome Biliopancreatic Carcinoma Patients With Two-marker Signature Based on ATF6α and p-p38 "STARD Compliant".

Biliopancreatic cancer is one of the most aggressive solid neoplasms, and incidence is rising worldwide. It is known that ATF6α is one of the transmembrane proteins that acts crucially in endoplasmic reticulum stress response, and knockdown induces apoptosis of pancreatic cells. Apart from this, p-p38 has been previously correlated with better outcome in pancreatic cancer. Interestingly, ATF6α knockdown pancreatic cells showed increased p-p38. The aim of this study was to evaluate the expression of these 2 proteins, p-p38 and ATF6α, and their correlation with the outcome of biliopancreatic adenocarcinoma patients. Samples from patients with biliopancreatic adenocarcinoma that underwent pancreaticoduodenectomy from 2007 to 2013 were used to construct a tissue microarray to evaluate p-p38 and ATF6α proteins by immunohistochemistry. We observed that both markers showed a tendency to impact in the time to recurrence; then a combination of these 2 proteins was analyzed. Combination of ATF6α(high) and p-p38(low) was strongly associated with a higher risk of recurrence (hazard ratio 2.918, P = 0.013). This 2-protein model remained significant after multivariate adjustment.We proposed a 2-protein signature based on ATF6α(high) and p-p38(low) as a potential biomarker of risk of recurrence in resected biliopancreatic adenocarcinoma patients.

Necrotising fasciitis of the lower limb due to perforated inguinal hernia.

Acute inguinal hernia complications (incarceration, strangulation) are relatively frequent conditions, especially in the elderly. Urgent surgery is the appropriate treatment if manual reduction is not achieved or strangulation or perforation is suspected. We present a 77-year-old patient with necrotising fasciitis of the lower limb as a consequence of extraperitoneal perforation of a sliding inguinal hernia. This devastating condition was diagnosed 20 h after the manual reduction of the hernia. Suspicion arose at the physical examination (crepitation, signs of cellulitis) and clinical deterioration of the patient, and was confirmed by computed tomography (CT) scanning. Urgent surgery was performed, including sigmoidectomy, debridement of the necrotic tissues of the medial and anterior thigh compartment, and fasciectomy, combined with optimal intensive care support. No signs of peritoneal or pelvic involvement were found. However, the comorbidities, advanced age and the progression of the disease led to fatal outcome. Early recognition of the complications of strangulated hernias is of vital importance for successful treatment in these cases, even if no signs of acute abdomen are present.

Adipose-derived stem cells in Crohn's rectovaginal fistula.

Therapeutic options for recto-vaginal fistula in the setting of Crohn's disease are limited and many data are available in the literature. The manuscript describes the history of a patient who has been the pioneer of our Clinical Trials in treating this disease in fistulizing Crohn's disease environment. We believe it is the first time that a patient with this disease has been treated by adipose-derived stem cells in allogeneic form. The conclusion of our study with Mary is that the use of mesenchymal stem cells derived from adipose tissue is secure, either in autologous or allogeneic form. Furthermore, we have proved that if we use multi-dose and multiple applications on a patient, it does not produce any adverse effect, which confirms us the safety of using these cells in patients at least in the fistulizing Crohn's disease environment.

A new bronchoscopic treatment of tracheomediastinal fistula using autologous adipose-derived stem cells.

Tracheal fistulas represent a challenging management problem. The standard treatment in most cases is based on surgical procedures. Various endoscopic treatment modalities have been proposed in patients at high surgical risk but the results are often unsatisfactory. The fistulas frequently recur with additional complications and sometimes death. The case history is reported of a patient with a tracheomediastinal fistula resulting from laser treatment of tracheal cancer. The fistula was treated by bronchoscopic injection of autologous adipose-derived stem cells (ASC) suspended in fibrin glue. The patient's stem cells were isolated from lipoaspirate according to a standard-ised procedure. No complications due to treatment with ASC occurred during the follow-up period and no fistula-related symptoms were detected. Postoperative bronchoscopic examination of the wall and base of the fistula revealed re-epithelialisation and neovascularisation that led to successful closure. To our knowledge, this is the first report of treatment of tracheal fistula by autologous cell therapy. Further studies are needed to confirm whether this new method should become routine practice.

Efficacy of parenteral administration of ivermectin in the control of strongylidosis in donkeys.

Investigations into the efficacy of parenteral ivermectin (Pandex) administration for strongylidosis control in donkeys were carried out. The preparation was applied subcutaneously at a dose of 0.2 mg/kg (1 ml/50 kg body weight). One day prior to the treatment and 14 days post-treatment, individual coprological samples were obtained for faecal nematode egg counts and larval culture. The study was performed on 263 donkeys originating from different regions of Bulgaria. Prior to the treatment and 20 days after that, blood samples were obtained from 64 previously infected animals for monitoring of changes in eosinophil leukocyte counts. The subcutaneous application of ivermectin had an efficacy of 96% in terms of reduction of faecal egg counts. In 92.2% of infected donkeys, a complete reduction of faecal eggs count occurred (0 eggs per gram of faeces epg), whereas in the remaining 7.8% of the infected donkeys, the egg counts were reduced by 72%. The reduction in faecal egg counts did not result in changes in eosinophil counts. The results obtained as well as the lack of local changes after the subcutaneous application of ivermectin in donkeys allow us to recommend its use for control of strongyles in donkeys.

Dynamical coupling of wind and ocean waves through wave-induced air flow.

Understanding the physical mechanisms behind the generation of ocean waves by wind has been a longstanding challenge. Previous studies have assumed that ocean waves induce fluctuations in velocity and pressure of the overlying air that are synchronized with the waves, and numerical models have supported this assumption. In a complex feedback, these fluctuations provide the energy for wave generation. The spatial and temporal structure of the wave-induced airflow therefore holds the key to the physics of wind-wave coupling, but detailed observations have proved difficult. Here we present an analysis of wind velocities and ocean surface elevations observed over the open ocean. We use a linear filter to identify the wave-induced air flow from the measurements and find that its structure is in agreement with 'critical-layer' theory. Considering that the wave-induced momentum flux is then controlled by the wave spectrum and that it varies considerably in vertical direction, a simple parameterization of the total air-sea momentum flux is unlikely to exist.

Statistical-uncertainty-based adaptive filtering of lidar signals.

An adaptive filter signal processing technique is developed to overcome the problem of Raman lidar water-vapor mixing ratio (the ratio of the water-vapor density to the dry-air density) with a highly variable statistical uncertainty that increases with decreasing photomultiplier-tube signal strength and masks the true desired water-vapor structure. The technique, applied to horizontal scans, assumes only statistical horizontal homogeneity. The result is a variable spatial resolution water-vapor signal with a constant variance out to a range limit set by a specified signal-to-noise ratio. The technique was applied to Raman water-vapor lidar data obtained at a coastal pier site together with in situ instruments located 320 m from the lidar. The micrometeorological humidity data were used to calibrate the ratio of the lidar gains of the H(2)O and the N(2) photomultiplier tubes and set the water-vapor mixing ratio variance for the adaptive filter. For the coastal experiment the effective limit of the lidar range was found to be approximately 200 m for a maximum noise-to-signal variance ratio of 0.1 with the implemented data-reduction procedure. The technique can be adapted to off-horizontal scans with a small reduction in the constraints and is also applicable to other remote-sensing devices that exhibit the same inherent range-dependent signal-to-noise ratio problem.