Laparoscopic hernia repair in children: does recreating the open operation improve outcomes? A systematic review.

PURPOSE: The use of laparoscopy for paediatric inguinal hernia repairs has increased significantly over the past 2 decades. However, there is significant variation in the reported recurrence rates in the literature, with many studies reporting higher rates than the open operation. This may be explained by the range of different techniques currently included under the term laparoscopic inguinal hernia repair. The purpose of this study is to determine whether dividing the hernia sac before ligation improves surgical outcomes following a paediatric laparoscopic inguinal hernia repair compared to ligation alone. METHODS: A systematic review of the literature was performed following PRISMA guidelines of all studies reporting the outcomes following paediatric laparoscopic inguinal hernia repair where the technique was recorded as laparoscopic suture ligation alone (LS) or laparoscopic sac division and suture ligation (LSDS). Studies were assessed for risk of bias and exclusion criteria included reported follow-up of less than 6 months. RESULTS: A total of 8518 LS repairs and 6272 LSDS repairs were included in the final analysis. LSDS repair was associated with a significantly lower recurrence rate (odds ratio 0.51, 95% CI 0.36-0.71, p = 0.001). There was no significant difference in the rates of testicular ascent or atrophy. CONCLUSION: Recreating the open operation by hernia sac division followed by suture ligation significantly reduces the risk of hernia recurrence.

Laparoscopic inguinal herniotomy: Recreating the open operation optimises outcomes.

BACKGROUND: Recent evidence suggests simple laparoscopic inguinal herniorrhaphy is associated with higher rates of recurrence and testicular ascent. We instigated a standardised approach to laparoscopic inguinal herniotomy (LIH), with circumferential sac division and 'purse-string' closure (4/0 monofilament polypropylene). An active follow-up programme was pursued. We reviewed our outcomes of this technique and compared them to an open herniotomy (OIH) cohort. METHODS: LIH patients were identified prospectively (2017-2021): OIH retrospectively from 2016. Risk factors for complications were defined: extremely to very preterm (< 32 weeks), emergency presentation with incarceration, and redo surgery for recurrence. Data are presented as median [IQR]. Comparisons used Fisher's exact and Mann-Whitney U tests: significance defined as p < 0.05. RESULTS: 192 inguinal herniae in 140 patients were included in the LIH group and 214 herniae in 179 patients in the OIH group. Groups were similar in age and gender. The LIH group had a significantly larger proportion of cases that were premature, had emergency surgery, or had redo surgery after previous OIH. Follow-up was 24.4 months [10.8-33.6] vs. 66.4 [64.5-68.5] (LIH vs. OIH). Hernia recurrence occurred in 2/192 (1.0%) vs. 4/214 (1.9%) (LIH vs. OIH), p = 0.69. There was one known case of testicular ascent after OIH but none in the LIH group. CONCLUSIONS: Recreation of the open herniotomy laparoscopically appears to confer excellent outcomes, with low rates of recurrence despite a high proportion of patients having known risk factors. Further long-term data on rates of testicular ascent after active follow-up are required.

Endoscopic vs laparoscopic paediatric gastrostomies: Time to change our practice?

BACKGROUND: Gastrostomy insertion is a common procedure for paediatric surgeons, with the percutaneous endoscopic gastrostomy (PEG) technique long favoured for its simplicity and speed. However, there is growing evidence to suggest that primary laparoscopic balloon gastrostomy (LBG) insertions may have lower complication rates. This study aimed to determine the relative safety and healthcare resource burden of PEG and LBG. METHODS: A retrospective review of all primary gastrostomy insertions (2011-2019). Primary outcome measures included return to theatre for emergency laparotomy and healthcare burden (total gastrostomy-related admissions, length of stay and total theatre utilisation). RESULTS: 338 PEGs and 277 LBGs were inserted with a minimum follow-up period of six months. Following PEG insertion 12/338(3.6%) children required an emergency laparotomy for gastrostomy-related complications. This compared to 2/277(0.7%) following LBG insertion (ARR2.8% (95%CI0.6-5.0), p < 0.0267). When considering all gastrostomy related admissions, there was no significant difference in total theatre utilisation (PEG = 85 [IQR58-117] minutes, LBG = 86 [IQR75-105] minutes, p = 0.12). However, PEGs were found to have an overall longer length of stay 4 [IQR3-7] vs 3 [IQR2-4] days. CONCLUSIONS: LBGs carry a significantly lower rate of major complications and are not associated with an increased healthcare burden. LBG should be considered as the first line method of gastrostomy insertion in children.

The von Willebrand factor D'D3 assembly and structural principles for factor VIII binding and concatemer biogenesis.

D assemblies make up half of the von Willebrand factor (VWF), yet are of unknown structure. D1 and D2 in the prodomain and D'D3 in mature VWF at Golgi pH form helical VWF tubules in Weibel Palade bodies and template dimerization of D3 through disulfides to form ultralong VWF concatemers. D'D3 forms the binding site for factor VIII. The crystal structure of monomeric D'D3 with cysteine residues required for dimerization mutated to alanine was determined at an endoplasmic reticulum (ER)-like pH. The smaller C8-3, TIL3 (trypsin inhibitor-like 3), and E3 modules pack through specific interfaces as they wind around the larger, N-terminal, Ca2+-binding von Willebrand D domain (VWD) 3 module to form a wedge shape. D' with its TIL' and E' modules projects away from D3. The 2 mutated cysteines implicated in D3 dimerization are buried, providing a mechanism for protecting them against premature disulfide linkage in the ER, where intrachain disulfide linkages are formed. D3 dimerization requires co-association with D1 and D2, Ca2+, and Golgi-like acidic pH. Associated structural rearrangements in the C8-3 and TIL3 modules are required to expose cysteine residues for disulfide linkage. Our structure provides insight into many von Willebrand disease mutations, including those that diminish factor VIII binding, which suggest that factor VIII binds not only to the N-terminal TIL' domain of D' distal from D3 but also extends across 1 side of D3. The organizing principle for the D3 assembly has implications for other D assemblies and the construction of higher-order, disulfide-linked assemblies in the Golgi in both VWF and mucins.

Recombinant factor VIII Fc fusion protein drives regulatory macrophage polarization.

The main complication of replacement therapy with factor in hemophilia A (HemA) is the formation of inhibitors (neutralizing anti-factor VIII [FVIII] antibodies) in ∼30% of severe HemA patients. Because these inhibitors render replacement FVIII treatment essentially ineffective, preventing or eliminating them is of top priority in disease management. The extended half-life recombinant FVIII Fc fusion protein (rFVIIIFc) is an approved therapy for HemA patients. In addition, it has been reported that rFVIIIFc may induce tolerance to FVIII more readily than FVIII alone in HemA patients that have developed inhibitors. Given that the immunoglobulin G1 Fc region has the potential to interact with immune cells expressing Fc receptors (FcRs) and thereby affect the immune response to rFVIII, we investigated how human macrophages, expressing both FcRs and receptors reported to bind FVIII, respond to rFVIIIFc. We show herein that rFVIIIFc, but not rFVIII, uniquely skews macrophages toward an alternatively activated regulatory phenotype. rFVIIIFc initiates signaling events that result in morphological changes, as well as a specific gene expression and metabolic profile that is characteristic of the regulatory type Mox/M2-like macrophages. Further, these changes are dependent on rFVIIIFc-FcR interactions. Our findings elucidate mechanisms of potential immunomodulatory properties of rFVIIIFc.

Management of suspected thyroglossal duct cysts.

AIM OF STUDY: The aim of this study was to evaluate management of children with an anterior midline neck swelling by establishing 1) whether a preoperative ultrasound scan (USS) was appropriately requested, performed and reported; 2) whether there was preoperative infection; 3) whether a Sistrunk procedure was performed; 4) the rate of thyroglossal duct cyst (TGDC) recurrence following simple excision vs. Sistrunk procedure. METHODS: A single centre retrospective study of children who underwent surgery for anterior midline neck swelling between April 2000 and May 2015 at our institution was performed. These were identified using a clinical coding system, and data were collected from electronic medical records, radiology, and histopathology reports. Recurrence rates between simple excision and Sistrunk groups were compared using Chi-square test. MAIN RESULTS: 227 patients were identified (115 male, 112 female). 169 (74%) had a preoperative USS. The presence of a thyroid gland was stated in 79% of USS reports. This increased to 92% when the requesting surgeon had specifically asked about this. 48 (21%) patients underwent simple excision, while 175 (77%) had a Sistrunk procedure. Recurrence was significantly more likely following simple excision than a Sistrunk procedure (29% vs 6.9%; P<0.0001). Of 25 TGDC recurrences, 9 (36%) had an inconclusive or alternative histopathological diagnosis at first operation. CONCLUSION: Preoperative USS should be performed in all patients with an anterior midline neck swelling. Appropriate requesting increases likelihood of a report confirming (or otherwise) the presence of a thyroid gland. A Sistrunk procedure is the operation of choice in all children presenting with an anterior midline neck swelling. The surgeon cannot reliably differentiate a TGDC from alternative pathology intraoperatively. LEVEL OF EVIDENCE: Treatment study: level IV.

Mortality and morbidity in oesophageal atresia.

BACKGROUND: Several classification systems exist to predict mortality in oesophageal atresia, the most widely quoted of these being over 20 years old. No classification system exists to predict morbidity. We sought to test whether these classification systems remain relevant and to determine whether they can be useful to predict morbidity. In addition, we aimed to identify independent risk factors for predicting mortality and morbidity. METHODS: Neonates presenting with oesophageal atresia over a 20-year period (1990-2010) were retrospectively reviewed. Discriminative statistical analysis compared the performance of current classification systems. Stepwise logistic regression analysis of the influence of perioperative risk factors on mortality and duration of ventilatory support and intensive care unit stay were performed. RESULTS: All classification systems predicted mortality in this series of 248 neonates. Birth weight, cardiac anomalies and pre-operative pneumonia were independent risk factors for predicting mortality in oesophageal atresia. The Waterston classification is the most useful classification for predicting post-operative morbidity in terms of length of hospital stay and time spent ventilated. CONCLUSION: Despite advances in the neonatal care of the very low birth weight infant and those with congenital cardiac disease, these conditions remain relevant in predicting mortality and morbidity in oesophageal atresia.

Extension of in vivo half-life of biologically active molecules by XTEN protein polymers.

XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted.

Morbidity and mortality in total esophagogastric dissociation: a systematic review.

BACKGROUND/PURPOSE: Total esophagogastric dissociation has been described as both a primary and a rescue procedure for patients with severe gastroesophageal reflux. Although most commonly used in the neurologically impaired, it has also been used in those with no neurological impairment. The main objective of this study was to determine morbidity and mortality for this procedure. METHODS: All published cases of esophagogastric dissociation in children were identified. Series were updated where possible by personal communication with the author. Patient characteristics, indications, morbidity, and mortality were analyzed. RESULTS: One hundred eighty-one cases were identified. One hundred seventeen were primary operations and 64 were rescue procedures. There were 29 (16.0%) early complications and 28 (15.5%) late complications with 6 (3.3%) deaths related to the procedure of a total of 35 deaths. Twenty-one patients (11.6%) required re-operation in the study periods. CONCLUSIONS: Esophagogastric dissociation has an acceptable morbidity and mortality. It is useful as both a primary and a rescue procedure.

Pneumonectomy: The final cut in a rare incidence of persistent bronchopleural fistula following empyema.

The incidence of necrotizing pneumonia and empyema complicated by bronchopleural fistula is rising. We describe the case of a 2-year-old boy who presented with empyema thoracis and necrotizing pneumonia who developed a bronchopleural fistula. At initial thoracotomy for decortication, necrotic lung was found and resected. He subsequently underwent further thoracotomy, prolonged chest tube drainage and endobronchial glue application attempts to close a bronchopleural fistula. The fistula was only sealed at third thoracotomy and completion pneumonectomy. This case highlights the potential challenges faced when dealing with air leaks in the setting of infection and we discuss the treatment options available.

Computed tomography in the assessment of suspected large bowel obstruction.

BACKGROUND: The aim of this study was to assess the efficacy of computed tomography (CT) scanning in the diagnosis of acute large bowel obstruction. METHODS: Forty-four patients (22 men; 22 women, ages 39-94 years, mean 71 years) with clinical features and abdominal radiographic findings suggesting acute large bowel obstruction (LBO) or pseudo-obstruction were examined with CT. Supine scans were obtained with i.v. contrast medium (unless contraindicated), but (in the majority) without oral contrast. Additional prone and/or decubitus scans were obtained in 33 patients when clarification of a possible transition point on the supine scan was required. CT diagnosis of LBO was made by finding a transition point +/- mass. Final diagnosis was confirmed by surgery, further imaging and/or clinical course. RESULTS: Twenty-two patients had proven mechanical acute LBO of whom 18 had an obstructing carcinoma; 22 patients had no mechanical obstruction. Sensitivity, specificity, Positive Predictive Value, Negative Predictive Value of CT for diagnosis of mechanical LBO were each 91%. Positive and negative likelihood ratios were 10.1 and 0.1, respectively. There were two false-negative CT scans, although one of these was reported as showing segmental mural thickening. A mass was identified on 14 of 17 patients with true-positive CT, subsequently found to have carcinoma. CONCLUSION: Computed tomography with additional selective prone and/or decubitus scanning is highly effective in the diagnosis of mechanical LBO. It is suggested that it replace contrast enema as the initial imaging method.