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.

Reading a preoperative CT scan to guide complex abdominal wall reconstructive surgery.

Computed tomography (CT) scanning is the imaging modality of choice when planning the overall management and operative approach to complex abdominal wall hernias. Despite its availability and well-recognised benefits there are no guidelines or recommendations regarding how best to read or report such scans for this application. In this paper we aim to outline an approach to interpreting preoperative CT scans in abdominal wall reconstruction (AWR). This approach breaks up the interpretive process into 4 steps-concentrating on the hernia or hernias, any complicating features of the hernia(s), the surrounding soft tissues and the abdominopelvic cavity as a whole-and was developed as a distillation of the authors' collective experience. We describe the key features that should be looked for at each of the four steps and the rationale for their inclusion.

Reporting guideline for interventional trials of primary and incisional ventral hernia repair.

BACKGROUND: Primary and incisional ventral hernia trials collect unstandardized inconsistent data, limiting data interpretation and comparison. This study aimed to create two minimum data sets for primary and incisional ventral hernia interventional trials to standardize data collection and improve trial comparison. To support these data sets, standardized patient-reported outcome measures and trial methodology criteria were created. METHODS: To construct these data sets, nominal group technique methodology was employed, involving 15 internationally recognized abdominal wall surgeons and two patient representatives. Initially a maximum data set was created from previous systematic and panellist reviews. Thereafter, three stages of voting took place: stage 1, selection of the number of variables for data set inclusion; stage 2, selection of variables to be included; and stage 3, selection of variable definitions and detection methods. A steering committee interpreted and analysed the data. RESULTS: The maximum data set contained 245 variables. The three stages of voting commenced in October 2019 and had been completed by July 2020. The final primary ventral hernia data set included 32 variables, the incisional ventral hernia data set included 40 variables, the patient-reported outcome measures tool contained 25 questions, and 40 methodological criteria were chosen. The best known variable definitions were selected for accurate variable description. CT was selected as the optimal preoperative descriptor of hernia morphology. Standardized follow-up at 30 days, 1 year, and 5 years was selected. CONCLUSION: These minimum data sets, patient-reported outcome measures, and methodological criteria have allowed creation of a manual for investigators aiming to undertake primary ventral hernia or incisional ventral hernia interventional trials. Adopting these data sets will improve trial methods and comparisons.

Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Recurrent intestinal fistulation after porcine acellular dermal matrix reinforcement in enteric fistula takedown and simultaneous abdominal wall reconstruction.

PURPOSE: Porcine acellular dermal matrix (PADM) has been promoted as a suitable material for the reinforcement of the abdominal wall in Ventral Hernia Working Group (VHWG) Grade 3/4 wounds by Ventral Hernia Working Group et al. (Surgery 148(3):544-548). We describe our experience of, and assess the mechanisms for the failure of PADM (PermacolTM) in intestinal and abdominal wall reconstruction (AWR) for enterocutaneous fistulation (ECF). METHODS: All patients referred to our unit who had PADM used for AWR and ECF were studied from a prospectively maintained database. Follow-up data until 31/12/2018 were analysed. PADM was explanted at further surgery and examined histologically. RESULTS: 13 patients, (median age-58.5 years) underwent AWR with PADM reinforcement. Twelve of these (92%) patients had developed abdominal wall defects (AWD) and ECF following complications of previous surgery. Six patients underwent fistula takedown and AWR with PADM, of which 5(83%) refistulated. Seven patients referred to us had already undergone similar procedures in their referring hospitals and had also refistulated. Median (range) time to fistulation after AWR with PADM was 17 (7-240) days. In all cases, PADM had been used to bridge the defect and placed in direct contact with bowel. At reconstructive surgery for refistulation, PADM was inseparable from multiple segments of small intestine, necessitating extensive bowel resection. Histological examination confirmed that the PADM almost completely integrated with the seromuscular layer of the small intestine. CONCLUSION: PADM may become inseparable from serosa of the human small intestinal serosa when it is left in the abdomen during reconstructive surgery. This technique is associated with recurrent intestinal fistulation and intestinal failure and should be avoided if at all possible.

The European Society of Paediatric Oncology Ependymoma-II program Core-Plus model: Development and initial implementation of a cognitive test protocol for an international brain tumour trial.

It is increasingly accepted that survival alone is an inadequate measure of the success of childhood brain tumour treatments. Consequently, there is growing emphasis on capturing quality of survival. Ependymomas are the third most frequently occurring brain tumours in childhood and present significant clinical challenges. European Society of Paediatric Oncology Ependymoma II is a comprehensive international program aiming to evaluate outcomes under different treatment regimens and improve diagnostic accuracy. Importantly, there has been agreement to lower the age at which children with posterior fossa ependymoma undergo focal irradiation from three years to either eighteen months or one year of age. Hitherto radiotherapy in Europe had been reserved for children over three years due to concerns over adverse cognitive outcomes following irradiation of the developing brain. There is therefore a duty of care to include longitudinal cognitive follow-up and this has been agreed as an essential trial outcome. Discussions between representatives of 18 participating European countries over 10 years have yielded European consensus for an internationally accepted test battery for follow-up of childhood ependymoma survivors. The 'Core-Plus' model incorporates a two-tier approach to assessment by specifying core tests to establish a minimum dataset where resources are limited, whilst maintaining scope for comprehensive assessment where feasible. The challenges leading to the development of the Core-Plus model are presented alongside learning from the initial stages of the trial. We propose that this model could provide a solution for future international trials addressing both childhood brain tumours and other conditions associated with cognitive morbidity.

Development and Validation of an Analytical Method to Quantitate Tris(chloroisopropyl)phosphate in Rat and Mouse Plasma using Gas Chromatography with Flame Photometric Detection.

Tris(chloropropyl)phosphate (TCPP) is an organophosphorus flame retardant (OPFR) and plasticizer increasingly used in consumer products and as a replacement for brominated flame retardants. Commercially available TCPP is a mixture of four structural isomers the most abundant of which is tris(1-chloro-2-propyl)phosphate (TCPP-1). Although there is a widespread use of TCPP and potential for human exposure, there is limited data on the safety or toxicity of TCPP. The National Toxicology Program is conducting long-term studies to examine the toxicity of the TCPP in rats after lifetime exposure, including perinatal oral exposure. Quantitative estimates of internal dose are essential to interpret toxicological findings in rodents. To aid in this, a method was fully validated to quantitate the most abundant isomer, TCPP-1, in female Harlan Sprague Dawley (HSD) rat and B6C3F1 mouse plasma with partial validation in male rat plasma, and male and female mouse plasma. The method used protein precipitation using trichloroacetic acid followed by the extraction with toluene, and analysis by gas chromatography with flame photometric detection. The performance of the method was evaluated over 5-70 ng TCPP-1/mL plasma. The method was linear (r ≥ 0.99), accurate (inter-day relative error: ≤ ± -7.2) and precise (inter-batch relative standard deviation: ≤27.5%). The validated method has lower limits of quantitation and detection of ~5 and 0.9 ng/mL, respectively, in female HSD rat plasma and can be used on samples as small as 50 µL demonstrating the applicability to plasma samples from toxicology studies.

Preoperative mechanical and oral antibiotic bowel preparation to reduce infectious complications of colorectal surgery - the need for updated guidelines.

BACKGROUND: Increasing evidence indicates that combined mechanical and oral antibiotic bowel preparation reduces the infectious complications of colorectal surgery. Anecdotal evidence suggests the combination is rarely used in the UK and Europe. AIM: To establish colorectal surgeons' current use and awareness of the benefits of such bowel preparation, and to identify decision-making influences surrounding preoperative bowel preparation. METHOD: An electronic survey was emailed to all members of the Association of Coloproctology of Great Britain and Ireland, and promoted via Twitter. FINDINGS: A total of 495 respondents completed the survey: 413 (83.2%) UK, 39 (7.9%) other European, 43 (8.7%) non-European. Respondents used oral antibiotics for 12-20% of cases. Mechanical bowel preparation (MBP), phosphate enema, and no preparation, respectively, ranged between 9 and 80%. Combined MBP and oral antibiotic bowel preparation ranged between 5.5 and 18.6%. Fifty-three percent (260/495) agreed that combined mechanical and oral antibiotic bowel preparation reduces surgical site infection; 32% (157/495) agreed that the combination reduces risk of anastomotic leak. Kappa statistics between 0.06 and 0.27 indicate considerable incongruity between surgeons' awareness of the literature, and day-to-day practice. Twenty-four percent (96/495) believed MBP to be incompatible with enhanced recovery after surgery (ERAS); 41% (204/495) believed that MBP delays return to normal intestinal function. CONCLUSIONS: Few UK and European colorectal surgeons use mechanical and oral antibiotic bowel preparation, despite evidence of its efficacy in reducing infectious complications. The influence of ERAS pathways and UK and European guidelines may explain this. In contradiction to the UK and Europe, North American guidelines recommend incorporating combined mechanical and oral antibiotic bowel preparation into ERAS programmes. This study suggests that future UK and European guidelines incorporate combined mechanical and oral antibiotic bowel preparation into the ERAS pathway.

Escalating-dose HLA-mismatched DLI is safe for the treatment of leukaemia relapse following alemtuzumab-based myeloablative allo-SCT.

Although the feasibility of using HLA-mismatched unrelated donors as an alternate graft source for haematopoietic SCT (HSCT) has been shown, little is known about the safety of HLA-mismatched DLI for the treatment of relapse. We examined the outcome of 58 consecutive leukaemia patients who received escalating-dose DLI for treatment of relapse after alemtuzumab-conditioned myeloablative unrelated donor HSCT at our institution. High-resolution HLA typing on stored DNA samples revealed mismatches in 28/58 patients who were considered HLA-matched at the time of transplantation. Following DLI from HLA-matched (10/10) (n=30) or -mismatched (7-9/10) (n=28) unrelated donors, we found no significant difference in the incidence of acute GVHD (17.2% versus 23.1%, P=0.59), probability of remission at 3 years (62.1% versus 63.9%, P=0.89) or 5-year OS (89.8% versus 77.7%, P=0.22). We conclude that escalating-dose DLI can be safely given to HLA-mismatched recipients following T-depleted myeloablative HSCT.

Ab externo scleral fixation of intraocular lens.

UNLABELLED: We describe an ab externo technique that facilitates IOL scleral fixation and reduces the risk associated with previous ab externo scleral fixation techniques. This technique uses a microvitreoretinal blade and an internal limiting membrane forceps to create sclerotomies and retrieve the suture, respectively. FINANCIAL DISCLOSURE: Dr. Cionni is a consultant to Morcher GmbH, Stuttgart, Germany. Dr. Crandall is a consultant to Alcon Laboratories, Inc., Ft. Worth, Texas, USA. No other author has a financial or proprietary interest in any material or method mentioned.

Autologous reconstruction of massive enteroatmospheric fistulation with a pedicled subtotal lateral thigh flap.

BACKGROUND: Reconstruction of massive contaminated abdominal wall defects associated with enteroatmospheric fistulation represents a technical challenge. An effective technique that allows closure of intestinal fistulas and reconstruction of the abdominal wall, with a good functional and cosmetic result, has yet to be described. The present study is a retrospective review of simultaneous reconstruction of extensive gastrointestinal tract fistulation and large full-thickness abdominal wall defects, using a novel pedicled subtotal thigh flap. METHODS: The flap, based on branches of the lateral circumflex femoral artery, was used to reconstruct the abdominal wall in six patients who were dependent on artificial nutritional support, with a median (range) of 4·5 (3-23) separate intestinal fistulas, within open abdominal wounds with a surface area of 564·5 (204-792) cm2. Intestinal reconstruction was staged, with delayed closure of a loop jejunostomy. Median follow-up was 93·5 (10-174) weeks. RESULTS: Successful healing occurred in all patients, with no flap loss or gastrointestinal complications. One patient died from complications of sepsis unrelated to the surgical treatment. All surviving patients gained complete nutritional autonomy following closure of the loop jejunostomy. CONCLUSION: Replacement of almost the entire native abdominal wall in patients with massive contaminated abdominal wall defects is possible, without the need for prosthetic material or microvascular free flaps. The subtotal pedicled thigh flap is a safe and effective method of providing definitive treatment for patients with massive enteroatmospheric fistulation.

Acanthamoeba and fungal keratitis in a woman with a history of Intacs corneal implants.

PURPOSE: To report a case of corneal perforation secondary to Acanthamoeba and fungal keratitis in a patient with a history of Intacs corneal implants. METHODS: The patient's history, clinical presentation, and pathologic analysis were reviewed. RESULTS: A 56-year-old woman with keratoconus was referred to the university eye center for a corneal perforation secondary to a chronic corneal ulcer initially diagnosed as herpes simplex keratitis. The patient had Intacs inserted in the same eye 14 months earlier, but had them removed approximately 1 month before her visit. After emergency keratoplasty, the patient's corneal tissue was sent for histopathologic examination, which showed an Acanthamoeba and fungal coinfection. CONCLUSIONS: Atypical sources of keratitis should be considered in patients with a chronic corneal ulcer and a history of Intacs corneal implants.

Prophylactic gatifloxacin therapy in prevention of bacterial keratitis in a rabbit laser in situ keratomileusis model.

PURPOSE: Use the ID(50) (infectious dose to 50% of experimental animals) to quantify the most effective prophylactic dosing regimen to use with gatifloxacin 0.3% (Zymar) for the prevention of keratitis in a rabbit laser in situ keratomileusis model of Staphylococcus epidermidis infection. SETTING: University Laboratory, University of Arizona, Tucson, Arizona, USA. METHODS: Two groups of rabbits were compared in each of 2 experiments that were separated by 12 months. In the first experiment, rabbits receiving no postoperative antibiotic therapy (Group 1) were compared with rabbits receiving postoperative antibiotic therapy (Group 2). In the second experiment, postoperative antibiotic therapy (Group 3) was compared with preoperative and postoperative antibiotic therapy (Group 4). All antibiotic regimens used gatifloxacin 0.3%. Before antibiotic therapy began, corneal pockets were created in the right eye of each rabbit and all rabbits received balanced salt solution (BSS) only or BSS and S epidermidis inoculations in the corneal pocket. Rabbits were monitored for corneal infiltrates after surgery. RESULTS: The ID(50) of the first, second, third, and fourth groups of rabbits was 10(2), 10(4), 10(5), and 10(7) organisms, respectively. The data showed a statistically significant difference between rabbits receiving BSS only and most rabbits receiving BSS plus inoculate at each postoperative measurement (P<.05). CONCLUSIONS: The findings suggest that the use of both preoperative and postoperative antibiotic therapy may be most effective in preventing infection. Postoperative antibiotic therapy increased the number of S epidermidis necessary to cause infection by at least 100-fold over no antibiotic intervention. Preoperative plus postoperative antibiotic therapy increased the number of bacteria necessary to cause infection by at least 100-fold over postoperative therapy alone and by more than 10000-fold over no antibiotic intervention.

Hidradenitis suppurativa: pathogenesis and management.

Hidradenitis suppurativa (HS) is a chronic disease manifested by recurrent abscesses, sinus tracts and scarring. It arises most commonly, however, not exclusive from apocrine gland bearing skin. This review article sets out to clarify the importance of early diagnosis, the pathogenesis and aetiology of HS, and evidence for medical and surgical therapies for this debilitating disease.HS is caused primarily by follicular occlusion with secondary involvement of the apocrine glands. The aetiology is still poorly understood. There is a genetic component with probable hormonal influence on gene expression. Shearing forces from obesity and tight clothing contribute to its development. Management should be appropriately tailored for the severity and distribution of HS as well as quality of life of the patient. Medical management with appropriate antibiotics, if initiated early, can be successful in mild to moderate severity HS as well as improving disease control prior to attempted curative surgery in severe HS. Other helpful measures include advice on lifestyle changes, intralesional steroids, systemic retinoids, hormonal manipulation, and a revival of interest in the use of radiotherapy for HS. While there is a place for 'conservative' surgical procedures (including CO(2) laser) in selected cases of mild to moderate HS, radical excision of all apocrine-bearing tissue is the definitive treatment. We advocate close interdisciplinary collaboration as well as a cautionary approach to timing and planning of surgery to minimise recurrence rates.

Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast.

Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Delta strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Delta mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.

Functional discovery via a compendium of expression profiles.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.