A comparison of patient-reported outcomes in patients undergoing abdominal wall repair with either synthetic or biosynthetic mesh: a pilot study.

PURPOSE: Repair of midline ventral incisional hernias (VIHR) requires mesh reinforcement. Mesh types can be categorised into synthetic, biosynthetic, or biological. There is a lack of evidence to support one type of mesh over another. The aim of this pilot study was to compare mesh sensation in patients having undergone elective open repair with synthetic or biosynthetic mesh. METHODS: Four years of prospectively collected data were retrospectively reviewed on 40 patients who had undergone VIHR, using either biosynthetic or synthetic mesh placed in the retromuscular plane. The decision on type of mesh used was governed by patient characteristics. Patients were invited to complete the Carolinas Comfort Scale (CCS) questionnaire, the higher the score indicating a poorer quality of life. The maximum length of follow-up was 36 months. RESULTS: Twenty patients received permanent synthetic and 20 biosynthetic mesh. There was no clinical evidence of hernia recurrence in either group in the short to medium term. Overall, 97% (39/40) patients reported an average of either no or mild symptoms (mean CCS score 17.9 of 115). Patients with a biosynthetic repair had a significant lower CCS at ≥ 18 months (p < 0.05). CONCLUSION: After VIHR, patients have low CCS scores, indicating good quality of life outcomes, in the short to medium term irrespective of the mesh used. However, biosynthetic mesh had lower CCS scores in the medium term. This may help surgeons and patients make better informed decisions about which mesh to use in their individual circumstances.

Delphi consensus statement for understanding and managing the subcostal hernia: subcostal hernias collaborative report (scholar study).

INTRODUCTION: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias. METHODS: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement. RESULTS: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary. CONCLUSION: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias.

Sixteen Years of Meiotic Silencing by Unpaired DNA.

The filamentous fungus Neurospora crassa possesses a process called meiotic silencing by unpaired DNA (MSUD). MSUD has a remarkable ability to scan homologous chromosomes for unpaired DNA during meiosis. After unpaired DNA is identified, MSUD silences all RNA from the unpaired DNA along with any RNA transcribed from homologous sequences at other locations in the genome, regardless of their pairing state. The mechanism by which unpaired DNA is detected is unknown. Unpaired DNA segments can be as short as 1.3kb, if not shorter, and DNA sequences with only a small level of polymorphism (6%) can be considered unpaired by MSUD. MSUD research has identified nine proteins required for full efficiency of the process, three of which are homologs of the canonical RNA interference (RNAi) proteins Dicer, Argonaute, and RNA-dependent RNA polymerase. Most MSUD proteins, including the RNAi homologs, appear to dock outside of the nuclear envelope during early stages of meiosis. Only two have been observed inside the nucleus, a low number given that the identification of unpaired DNA and the triggering of silencing must begin within this location. These two proteins may participate in the unpaired DNA detection process. Recent evidence indicates that the search for unpaired DNA is spatially constrained, possibly because of restrictions on the arrangement of chromatin loops during or after homolog pairing. This review attempts to provide a complete analysis of past, present, and future directions of MSUD research, starting with its discovery during a search for a conserved regulator of fungal development and ending with some benefits the process may provide to MSUD capable organisms.

Ligation of the intersphincteric fistula tract in the management of anal fistula. A systematic review.

AIM: Over the last 5 years, the ligation of the intersphincteric fistula tract (LIFT) procedure has become increasingly popular as a sphincter-preserving technique for the treatment of anal fistula. The aim of this article was to review the published literature on the LIFT procedure. METHOD: The Cochrane database and EMBASE were searched from January 1980 to November 2012, and PubMed from January 1966 to November 2012. All peer-reviewed studies that investigated the LIFT procedure for the treatment of anal fistula were eligible for inclusion. Technical notes, commentaries, letters and meeting abstracts were excluded. The primary outcome measured was the overall fistula closure rate in relation to the length of follow-up. RESULTS: Twenty-nine articles were originally identified using the search criteria. Thirteen were finally included for analysis. Sample sizes ranged from 18 to 93 patients, with a pooled total of 498. Most fistulae, 494 (99%), were of cryptoglandular aetiology, of which 470 (94%) were transsphincteric. Overall success rates ranged from 40 to 95%, with a pooled success of 71% (352 of 495 patients; 3 of 498 were lost to follow-up). Follow-up ranged from 1 to 55 months, with a reported mean or median of 4 to 19.5 months. One hundred and eighty-three patients were formally assessed for continence, out of whom 11 (6%) had a minor disturbance. CONCLUSION: Overall the systematic review shows that the LIFT procedure appears to be an effective sphincter-conserving approach for the treatment of transsphincteric anal fistula with a pooled healing rate of 71% over a mean or median follow-up period ranging from 4 to 19.5 months.

Novel biological strategies in the management of anal fistula.

BACKGROUND: The mostly widely studied biomaterials for the sphincter sparing treatment of anal fistulas are fibrin glue and the anal fistula plug (AFP). However their overall mean clinical success is only 50-60%. As the understanding of the pathology of anal fistula, wound healing and the host response to materials has improved, so new biological sphincter-sparing strategies have been developed. The aim of this review is to assess the safety and efficacy of these novel techniques. METHOD: PubMed, the Cochrane database and EMBASE were independently searched. All studies that investigated the potential of a biomaterial (defined as any synthetic or biologically derived substance in contact with host tissue) to augment the healing of anal fistula without sphincter division were included. Studies solely describing the role of fibrin glue or an AFP were excluded. Data extraction included type of material, fistula aetiology, treatment of the primary tract, fistula healing, incontinence, duration of follow-up and any specific complications. Systematic quality assessment of the included articles was performed. RESULTS: Twenty-three articles were finally selected for review. These included a variety of biological and synthetic systems that were employed to deliver selected components of the extracellular matrix, growth factors, cytokines, stem cells or drugs to the fistula tract. CONCLUSION: To date no study matches fistulotomy with regard to long-term fistula eradication rate. This is probably due to implant extrusion, inadequate track preparation or an unsuitable material. Future techniques need to address all these issues to ensure success. Success should be validated by MRI or long-term follow-up.

Management of idiopathic anal fistula using cross-linked collagen: a prospective phase 1 study.

AIM: Fibrin glue and porcine intestinal submucosa are used in novel sphincter-preserving techniques to heal anal fistulae. However, their success is highly variable and decreases with the length of follow up. The aim of this study was to assess the safety, feasibility and potential efficacy of another novel agent, cross-linked collagen, in two different physical formats, to heal anal fistulae. METHOD: Prospectively recruited patients underwent symptom, continence and anal physiology assessments and magnetic resonance imaging. Patients with secondary tracts or acute sepsis were excluded. At operation, participants were randomized to receiving a solid collagen implant or collagen fibres suspended in fibrin glue. Follow up included repeat symptom, continence and physiological assessments at 3 months, and regular clinical review thereafter. RESULTS: Twenty-nine of 43 entrants were eligible for inclusion. Thirteen patients received the collagen implant, and 16 collagen-fibrin glue. Three months postoperation, no patient experienced acute sepsis or continence disturbance, and sphincter function and integrity were unchanged. At 29 months, 12 of 15 (one lost to follow up) patients treated with collagen-fibrin glue were healed, compared with seven of 13 who received the implant. CONCLUSION: In the short-to-medium term, both techniques are safe and equally effective. The results justify continued research into the use of biomaterials to heal anal fistulae.

Parastomal hernia prevention using a novel collagen implant: a randomised controlled phase 1 study.

BACKGROUND: Parastomal hernias can be prevented or repaired using synthetic mesh; however, reported complications include infection, fibrosis and potential bowel erosion. The study aim was to assess the safety, feasibility and potential efficacy of using a prophylactic collagen implant. METHODS: Twenty patients undergoing defunctioning stomas were randomised to a conventional procedure or reinforcement with the implant. Follow-up included regular symptom questionnaires, clinical examination, stoma site ultrasound, and serum inflammatory markers. RESULTS: Ten patients (four males; mean BMI 26.3) had a conventional stoma, and ten (three males; mean BMI 26.3) received the implant. At a median of 6.5 months follow-up, a parastomal hernia was clinically evident in three of ten patients without the implant, and in none of ten patients with the implant. There were no clinical complications, ultrasound evidence of chronic seromas or serological evidence of a systemic inflammatory response. CONCLUSIONS: Xenogeneic collagen has been demonstrated to aid soft tissue reinforcement. In this study, in contrast to published data relating to the use of conventional synthetic mesh, there were no complications related to infection or the implant's proximity to the bowel. This trial demonstrates that the implant is safe, feasible to use and has the potential to prevent parastomal herniation.

Human in vivo cellular response to a cross-linked acellular collagen implant.

BACKGROUND: Hernia surgery, in particular parastomal hernia mesh repair and new techniques for hernia prevention, require novel biomaterials that avoid fibrosis and potential bowel erosion, while retaining adequate strength for their intended purpose. The aim was to evaluate the human host response to an acellular porcine-derived cross-linked collagen implant. METHODS: In a prospective pilot study on prevention of parastomal herniation, 15 patients undergoing loop stoma formation had an implant placed within the anterior abdominal wall. Histopathology and immunohistochemistry were performed to analyse the implant qualitatively and, where appropriate, quantitatively for biocompatibility, degradation, cellular infiltration, neo-extracellular matrix (ECM) formation and neovascularization. RESULTS: At a median of 7 (range 1-8) months, 12 of 15 patients had stoma reversal and 11 implant biopsies were obtained. In biopsies from ten of the 11 patients all responses were limited to the periphery of the implant and native pores. There was a minimal inflammatory response and minimal degradation of the implant. Fibroblastic and neovascular infiltration were noted, as was matrix metalloproteinase 1 activity with organized deposition of host collagen, fibronectin and laminin. CONCLUSION: The collagen implant demonstrated excellent biocompatibility and resistance to degradation in most patients. However, fibrovascular in-growth and ECM deposition were limited. This implant has excellent potential for soft tissue reinforcement.

Aspergillus mycoviruses are targets and suppressors of RNA silencing.

RNA silencing can function as a virus defense mechanism in a diverse range of eukaryotes, and many viruses are capable of suppressing the silencing machinery targeting them. However, the extent to which this occurs between fungal RNA silencing and mycoviruses is unclear. Here, three Aspergillus dsRNA mycoviruses were partially characterized, and their relationship to RNA silencing was investigated. Aspergillus virus 1816 is related to Agaricus bisporus white button mushroom virus 1 and suppresses RNA silencing through a mechanism that alters the level of small interfering RNA. Aspergillus virus 178 is related to RNA virus L1 of Gremmeniella abietina and does not appear to affect RNA silencing. The third virus investigated, Aspergillus virus 341, is distantly related to Sphaeropsis sapinea RNA virus 2. Detection of mycovirus-derived siRNA from this mycovirus demonstrates that it is targeted for degradation by the Aspergillus RNA silencing machinery. Thus, our results indicate that Aspergillus mycoviruses are both targets and suppressors of RNA silencing. In addition, they suggest that the morphological and physiological changes associated with some mycoviruses could be a result of their antagonistic relationship with RNA silencing.

RNA silencing gene truncation in the filamentous fungus Aspergillus nidulans.

The genus Aspergillus is ideally suited for the investigation of RNA silencing evolution because it includes species that have experienced a variety of RNA silencing gene changes. Our work on this subject begins here with the model species Aspergillus nidulans. Filamentous ascomycete fungi generally each encode two of the core RNA silencing proteins, Dicer and Argonaute, but A. nidulans appears to have lost one of each to gene truncation events. Although a role in growth, development, or RNA silencing was not detected for the truncated genes, they do produce spliced and poly(A)-tailed transcripts, suggesting that they may have an undetermined biological function. Population analysis demonstrates that the truncated genes are fixed at the species level and that their full-length orthologs in a closely related species are also unstable. With these gene truncation events, A. nidulans encodes only a single intact Dicer and Argonaute. Their deletion results in morphologically and reproductively normal strains that are incapable of experimental RNA silencing. Thus, our results suggest that the remaining A. nidulans RNA silencing genes have a "nonhousekeeping" function, such as defense against viruses and transposons.

Straight to test. Results of a pilot study in a hospital serving an inner city population.

OBJECTIVE: The main aims of the study were to determine the frequency with which two-week wait (2ww) referrals for colorectal cancer (CRC) could proceed directly to straight to test (STT), and the potential improvement in time to diagnosis. METHOD: A telephone interview was attempted in all 2ww referrals not requiring an advocate and under 80 years. Data were assessed according to a test protocol, and where indicated a potential slot for the appropriate investigation was recorded (virtual test). All patients proceeded to clinic, following which differences in time from GP referral to virtual compared with actual requested test, and any discrepancies between virtual and requested tests were analysed. RESULTS: Between 8th January and 16th February 2007, there were 42 2ww referrals. Twenty-one patients were contacted, of whom 14 were suitable for STT: 13 virtual colonoscopies and one CT scan were booked. Following out-patient consultation, eight colonoscopies; three flexible sigmoidoscopies, one barium enema, and two CT scans were actually booked. There was a difference of 15.5 days between the median times of the virtual and actual test. During this 6-week period a total of nine patients were diagnosed with CRC, of whom three were referred via the 2ww pathway, but none were suitable for STT. CONCLUSIONS: This 'straight to test' pilot study suggests a potential strategy for reducing the time to diagnosis and therefore first treatment of those identified with CRC, and offers a methodology for individual hospitals to assess their suitability to employ such a strategy.

The Snug Seton: short and medium term results of slow fistulotomy for idiopathic anal fistulae.

OBJECTIVE: To assess the short and intermediate outcomes of a modification of the traditional cutting seton technique, using a 'snug' silastic seton, to treat idiopathic anal fistulae. PATIENTS AND METHODS: Between August 1997 and December 2002, 35 patients with idiopathic fistulae (4 female; age 26-76 years) underwent insertion of a 'snugly' tied 1 mm silastic seton (silicone nerve vessel retractor, Medasil), as definitive treatment. Short-term assessment was performed by case note review. Patients were subsequently invited to participate in a medium-term review. RESULTS: Twenty-nine patients' notes (3 female) were available for short-term analysis. Fistulae were classified as intersphincteric (9) and transsphincteric (20). The seton spontaneously cut out in 15/29 (52%) after a median of 24 weeks. In 14 patients the seton enclosed residual tissue (< 5 mm) required division as a day case procedure, at a median of 35 weeks. All fistulae healed but 10/29 (34%) patients (1 female; 8 transsphincteric) experienced minor incontinence. Sixteen patients participated in a medium-term review at a median of 42 months; 7 had experienced early continence disturbance. No patient suffered recurrence, but minor incontinence persisted in 4/16 (25%) patients (0 females; 3 transsphincteric). All patients were at least 'satisfied' with the outcome. CONCLUSION: In the short and medium term, the 'snug' seton is a safe and effective addition to the fistula surgeon's armamentarium.

RNA silencing in Aspergillus nidulans is independent of RNA-dependent RNA polymerases.

The versatility of RNA-dependent RNA polymerases (RDRPs) in eukaryotic gene silencing is perhaps best illustrated in the kingdom Fungi. Biochemical and genetic studies of Schizosaccharomyces pombe and Neurospora crassa show that these types of enzymes are involved in a number of fundamental gene-silencing processes, including heterochromatin regulation and RNA silencing in S. pombe and meiotic silencing and RNA silencing in N. crassa. Here we show that Aspergillus nidulans, another model fungus, does not require an RDRP for inverted repeat transgene (IRT)-induced RNA silencing. However, RDRP requirements may vary within the Aspergillus genus as genomic analysis indicates that A. nidulans, but not A. fumigatus or A. oryzae, has lost a QDE-1 ortholog, an RDRP associated with RNA silencing in N. crassa. We also provide evidence suggesting that 5' --> 3' transitive RNA silencing is not a significant aspect of A. nidulans IRT-RNA silencing. These results indicate a lack of conserved kingdom-wide requirements for RDRPs in fungal RNA silencing.

Fibrin glue in the management of anal fistulae.

OBJECTIVE: Fibrin glue has been used as a sphincter sparing approach for the treatment of anal fistulae for two decades. However, there is uncertainty about its short and long-term efficacy. The objective of this review was to ascertain the role of fibrin glue in the management of anal fistulae, including assessment of recurrence rates, continence disturbance and other complications. METHODS: We searched Medline (January 1966 to February 2004), the Cochrane database, and EMBASE using the terms anal fistulae, fistula-in-ano, and fibrin glue. Relevant papers from the reference lists of these articles and from the authors' personal collections were also reviewed. A systematic review of all articles relating to the use of fibrin glue in the treatment of anal fistulae was performed. This included 19 studies. Reviewers performed data extraction independently. Outcomes evaluated included recurrence rates, continence disturbance, septic complications, adverse drug reactions, and duration of follow-up. Heterogeneity of the clinical trials made direct comparisons difficult and meta-analysis impossible. RESULTS: The success rates reported in published studies range from 0% to 100%. Differences in patient selection (including fistula aetiology and type), treatment protocols, and follow-up duration may contribute to such diverse results. CONCLUSIONS: Fibrin glue is simple to use, has a minimal morbidity and should not affect later treatment options in the event of its failure. It is therefore theoretically attractive as a first line treatment in the management of those types of anal fistula in which it has been shown to work. However, further research into 'biological' glues is merited and these subject to randomised controlled study.