Sacrococcygeal teratomas: midline reconstruction improves cosmesis without compromising outcomes.

AIM: Several studies have addressed the long-term functional, psychosexual and psychosocial outcomes following sacrococcygeal teratoma (SCT) excision. It is well reported that the classical chevron incision and reconstruction can leave a cosmetically unsatisfactory result; however, there is little in the literature focussed on improving this outcome. In our institution the preference is to perform a midline reconstruction, where possible, this is felt to improve appearance without compromising the oncological or functional outcome. The aim of this study was to evaluate patient-perceived cosmetic outcomes of the midline reconstruction. METHODS: All patients undergoing surgery for SCT between 2007 and 2020 were included in the study. Patient demographics, operation type, functional outcome and recurrence were all recorded. The primary outcome measure was patient/parent satisfaction with the cosmetic appearance. This was assessed using both qualitative and quantitative methodologies. Following ethical approval parents were asked questions from two existing validated patient outcome questionnaires: "Patient and Observer Scar Assessment Scale" (POSAS) v2.0 and the "Patient Scar Assessment Questionnaire". RESULTS: Thirty-two patients underwent surgery at our institution for SCT during the study period. Twenty-four had a posterior approach with midline reconstruction, two laparotomy and excision (excluded from this study) and six had a combined approach. Median follow-up was 35 months (8.5-96 months). There were no recurrences. 4/30 (13%) have persistent urological symptoms, and 1/30 (3%) has constipation requiring bowel management. Questionnaires were sent to 26/30 families with a 77% return rate. Median total score was 11 (7.4-17.5) on a 60-point scale (6, as normal skin, 60, worst imaginable scar). Twenty (95%) reported that the scar never affects the child's activities and 15 (71%) said they are "not at all" conscious of the scar. CONCLUSION: Scars can lead to an array of cosmetic, functional, and psychological consequences and as such consideration needs to be given to scarring following surgery for sacrococcygeal teratomas. This study demonstrates that a midline reconstruction produces a cosmetically favourable outcome. We, therefore, recommend where appropriate a midline reconstruction should be considered for SCT.

Congenital infantile fibrosarcoma of the colon: a case series and literature review.

Congenital infantile fibrosarcoma is rare and only three cases affecting the colon have previously been reported. We describe two further cases that presented in the neonatal period and were both successfully treated with surgical excision and have no evidence of recurrence or metastasis at 31 and 27 months follow-up, respectively.

Paediatric angiodysplasia of the jejunum: a case report and review of the literature.

Gastrointestinal angiodysplasia (GIAD) of the jejunum is a rare cause of acute upper and lower gastrointestinal bleeding in the paediatric population. This is the case of a previously well 10-year-old girl who presented with acute rectal haemorrhage, haematemesis and syncope. Despite an exploratory laparotomy, the cause of bleeding remained unknown. A computerized tomography angiogram was performed once she was haemodynamically stable. It indicated bleeding in the jejunum. Repeat laparotomy was performed including enterotomy, copious small bowel washout and visualization of the whole small bowel. The lesion was identified at approximately 100 cm from the duodenojejunal flexure and confirmed by isolating the lesion and testing for bleeding. A 30 cm length of jejunum was resected and primary anastomosis performed. She recovered well and was discharged three days postoperatively. She remained well at six-month follow-up. This case highlights the importance of considering upper GIAD in an acute paediatric gastrointestinal bleed and the way in which surgical management can prevent a potentially fatal outcome.

In transit metastases in children, adolescents and young adults with localized rhabdomyosarcoma of the distal extremities: Analysis of the EpSSG RMS 2005 study.

In-transit metastases (ITM) are defined as metastatic lymph nodes or deposits occurring between the primary tumor and proximal draining lymph node basin. In extremity rhabdomyosarcoma (RMS), they have rarely been reported. This study evaluates the frequency, staging and survival of patients with ITM in distal extremity RMS. METHODS: Patients with extremity RMS distal to the elbow or knee, enrolled in the EpSSG RMS 2005 trial between 2005 and 2016 were eligible for this study. RESULTS: One hundred and nine distal extremity RMS patients, with a median age of 6.2 years (range 0-21 years) were included. Thirty seven of 109 (34%) had lymph node metastases at diagnosis, 19 of them (51%) had ITM, especially in lower extremity RMS. 18F-FDG-PET/CT detected involved lymph nodes in 47% of patients. In patients not undergoing 18F-FDG-PET/CT lymph node involvement was detected in 22%. The 5-yr EFS of patients with ITM vs proximal lymph nodes vs combined proximal and ITM was 88.9% vs 21.4% vs 20%, respectively (p = 0.01) and 5-yr OS was 100% vs 25.2% vs 15%, respectively (p = 0.003). CONCLUSION: Our study showed that in-transit metastases constituted more than 50% of all lymph node metastases in distal extremity RMS. 18F-FDG-PET/CT improved nodal staging by detecting more regional and in-transit metastases. Popliteal and epitrochlear nodes should be considered as true (distal) regional nodes, instead of in-transit metastases. Biopsy of these nodes is recommended especially in distal extremity RMS of the lower limb. Patients with proximal (axillary or inguinal) lymph node involvement have a worse prognosis.

Ileocaecal valve: how important is it?

PURPOSE: Our aim was to investigate the importance of the ileocaecal valve and its reconstruction in patients that are not suffering from short bowel syndrome and Crohn's disease. METHODS: Casenotes of 99 children with hemicolectomy and 24 children with terminal ileal resection were reviewed and sorted into three groups. Group 1: ileocaecal valve resection (limited hemicolectomy), Group 2: hemicolectomy, Group 3: terminal ileal resection between 10 and 25 cm. Patients with Crohn's, short bowel syndrome and incomplete follow-up were excluded. RESULTS: Chronic diarrhoea was documented in 7/26 cases (27%) in Group 1, 6/23 patients (26%) in Group 2, and none of the 13 patients had diarrhoea in Group 3. Pearson Chi-square test showed significant difference between Group 1 and Group 3 (p = 0.038) and between Group 2 and Group 3 (p = 0.043). But there was no significant difference between Group 1 and Group 2 (p = 0.947). CONCLUSION: Chronic diarrhoea is a significant complication after limited hemicolectomy not only in Crohn's disease and short bowel syndrome. This is likely to originate from the loss of the ileocaecal valve itself rather than the loss of the ileal or colonic segment. Our results justify attempts to reconstruct the ileocaecal valve.

Stomatal vs. genome size in angiosperms: the somatic tail wagging the genomic dog?

BACKGROUND AND AIMS: Genome size is a function, and the product, of cell volume. As such it is contingent on ecological circumstance. The nature of 'this ecological circumstance' is, however, hotly debated. Here, we investigate for angiosperms whether stomatal size may be this 'missing link': the primary determinant of genome size. Stomata are crucial for photosynthesis and their size affects functional efficiency. METHODS: Stomatal and leaf characteristics were measured for 1442 species from Argentina, Iran, Spain and the UK and, using PCA, some emergent ecological and taxonomic patterns identified. Subsequently, an assessment of the relationship between genome-size values obtained from the Plant DNA C-values database and measurements of stomatal size was carried out. KEY RESULTS: Stomatal size is an ecologically important attribute. It varies with life-history (woody species < herbaceous species < vernal geophytes) and contributes to ecologically and physiologically important axes of leaf specialization. Moreover, it is positively correlated with genome size across a wide range of major taxa. CONCLUSIONS: Stomatal size predicts genome size within angiosperms. Correlation is not, however, proof of causality and here our interpretation is hampered by unexpected deficiencies in the scientific literature. Firstly, there are discrepancies between our own observations and established ideas about the ecological significance of stomatal size; very large stomata, theoretically facilitating photosynthesis in deep shade, were, in this study (and in other studies), primarily associated with vernal geophytes of unshaded habitats. Secondly, the lower size limit at which stomata can function efficiently, and the ecological circumstances under which these minute stomata might occur, have not been satisfactorally resolved. Thus, our hypothesis, that the optimization of stomatal size for functional efficiency is a major ecological determinant of genome size, remains unproven.

Ovarian tumors in children: how common are lesion recurrence and metachronous disease? A UK CCLG Surgeons Cancer Group nationwide study.

BACKGROUND: Ovarian tumors in children are rare, mature teratoma being the most common histological entity. Robust guidelines to aid patient follow-up after resection are distinctly lacking. Although mature teratoma has a very good prognosis following complete resection, small studies have reported the occurrence of metachronous disease and recurrence to a variable degree (2.5-23% of patients). Nevertheless, there are surgeons who recommend no follow-up is required for these children after primary tumor resection. We investigated the incidence of (i) recurrence and (ii) metachronous disease in pediatric patients following ovarian tumor resection. METHODS: Retrospective multicenter study amongst UK pediatric surgical oncology centers. Females <16 years with diagnosis of ovarian tumor from 2006 to 2016 were included. Functional/neonatal ovarian cysts were excluded. RESULTS: Three hundred ten patients with ovarian tumors treated at 12 surgical oncology centers were identified. Mean age at surgery was 11 years [IQR 8-14]. Most common diagnosis were mature teratoma (57%, 177 cases), immature teratoma (10.9%, 34 cases) and serous cystadenoma (7.7%, 24 cases). 8.1% (25 cases) of all females were identified with tumor recurrence/ metachronous disease. 5.1% (9 cases) of patients with mature teratoma had recurrent/ metachronous disease. Most of these patients were diagnosed at routine clinic follow-up. CONCLUSION: Our study clearly shows that ovarian tumor recurrence(s) and metachronous disease occur, even in "benign" ovarian tumors. We recommend female pediatric patients should have robust follow-up care plans after primary diagnosis and resection of ovarian tumor(s). LEVEL OF EVIDENCE STATEMENT: This is a level II evidence study. It is a retrospective multicentre collaborative study which summarizes data from a national cohort of children.

Regulation of the higher-order structure of chromatin by histones H1 and H5.

Chicken erythrocyte chromatins containing a single species of linker histone, H1 or H5, have been prepared, using reassembly techniques developed previously. The reconstituted complexes possess the conformation of native chicken erythrocyte chromatin, as judged by chemical and structural criteria; saturation is reached when two molecules of linker histone are bound per nucleosome, as in native erythrocyte chromatin, which the resulting material resembles in its appearance in the electron microscope and quantitatively in its linear condensation factor relative to free DNA. The periodicity of micrococcal nuclease-sensitive sites in the linker regions associated with histone H1 or H5 is 10.4 base pairs, suggesting that the spatial organization of the linker region in the higher-order structure of chromatin is similar to that in isolated nucleosomes. The susceptible sites are cut at differing frequencies, as previously found for the nucleosome cores, leading to a characteristic distribution of intensities in the digests. The scission frequency of sites in the linker DNA depends additionally on the identity of the linker histone, suggesting that the higher-order structure is subject to secondary modulation by the associated histones.

Retroviral DNA integration directed by HIV integration protein in vitro.

Efficient retroviral growth requires integration of a DNA copy of the viral RNA genome into a chromosome of the host. As a first step in analyzing the mechanism of integration of human immunodeficiency virus (HIV) DNA, a cell-free system was established that models the integration reaction. The in vitro system depends on the HIV integration (IN) protein, which was partially purified from insect cells engineered to express IN protein in large quantities. Integration was detected in a biological assay that scores the insertion of a linear DNA containing HIV terminal sequences into a lambda DNA target. Some integration products generated in this assay contained five-base pair duplications of the target DNA at the recombination junctions, a characteristic of HIV integration in vivo; the remaining products contained aberrant junctional sequences that may have been produced in a variation of the normal reaction. These results indicate that HIV IN protein is the only viral protein required to insert model HIV DNA sequences into a target DNA in vitro.

Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases.

HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 A resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with a extensive solvent-inaccessible interface of 1300 A2 per monomer.

Retroviral integrases and their cousins.

The recently determined structures of the catalytic domains of HIV integrase, avian sarcoma virus integrase and the Mu transposase are strikingly similar to each other and also exhibit significant similarity to several nucleases. All these enzymes of cut polynucleotides, leaving 3'OH and 5'PO4 groups. The integrase and transposase also possess a strand-transfer activity that splices DNA. The structural similarities among members of this superfamily of polynucleotidyl transferases suggest that they share a similar mechanism of catalysis.

Laparoscopic repair of late presenting congenital diaphragmatic hernia.

Congenital diaphragmatic hernia usually presents in the neonatal period, with delayed presentation being uncommon. Traditionally repair was performed by laparotomy or thoracotomy. We have performed laparoscopic repair of a previously undiagnosed congenital diaphragmatic hernia that presented acutely in a 10-year-old male. Laparoscopic repair of late-presenting congenital diaphragmatic hernia is a safe and effective approach even in an emergency. The laparoscopic approach has advantages including reduced hospital stay, excellent visualisation of the defect even for obese patients, and improved cosmesis.

Children's surgery performed by adult general surgeons in Scotland: the present and future.

OBJECTIVE: The aim of this study was to determine the extent and the future of paediatric surgery performed in Scotland outside of the designated surgical paediatric centres. MATERIALS AND METHODS: An anonymous questionnaire was sent to all 111 Scottish members of the Association of Surgeons of Great Britain and Ireland. There was a response rate of 69%. RESULTS: Overall, 45% of responders operated on children. This was independent of the surgeon's age but was related to the type of hospital that the surgeon worked in. Eighty-four per cent of responders had a lower age limit under which they would not operate and 94% stated that there were specific circumstances where they would not operate. A mean of 18.5 elective procedures (range 0-250, median two) and six emergency procedures (range 0-30, median five) were carried out by each surgeon operating on children under the age of five per annum. Only 13% of responders thought that their successor would operate on children. CONCLUSIONS: Non-specialist paediatric surgery in Scotland is currently provided by a significant number of surgeons whose successors will not continue to provide a comparative paediatric service. This has implications for local provision of care, emergency management and capacity of existing children's hospitals in the future.

Solution structure of the His12 --> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium.

The solution structure of His12 --> Cys mutant of the N-terminal zinc binding domain (residues 1-55; IN(1-55)) of HIV-1 integrase complexed to cadmium has been solved by multidimensional heteronuclear NMR spectroscopy. The overall structure is very similar to that of the wild-type N-terminal domain complexed to zinc. In contrast to the wild-type domain, however, which exists in two interconverting conformational states arising from different modes of coordination of the two histidine side chains to the metal, the cadmium complex of the His12 --> Cys mutant exists in only a single form at low pH. The conformation of the polypeptide chain encompassing residues 10-18 is intermediate between the two forms of the wild-type complex.

Bipartite anterior extraperitoneal teratoma: evidence for the embryological origins of teratomas?

Teratomas are thought to arise from totipotent primordial germ cells (PGCs) Dehner (1983) which may miss their target destination Moore and Persaud (1984). Teratomas can occur anywhere from the brain to the coccygeal area but are usually in the midline close to the embryological position of the gonadal ridges Bale (1984), Nguyen and Laberge (2000). We report a case of a bipartite anterior extraperitoneal teratoma. This is an unusual position for a teratoma, but one which may support the "missed target" theory of embryology.

Surgical implications of the Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is a syndrome of rare multiple congenital anomalies/mental retardation associated with low plasma cholesterol levels. Prior to receiving the diagnosis of SLOS, affected children may present as a neonatal surgical emergency with ambiguous genitalia, Hirschsprung's disease, and pyloric stenosis. We present two fatal cases of SLOS with near-total Hirschsprung's disease; the surgical, anaesthetic, and medical aspects of the cases are discussed, and a literature review is presented.