Theatre of paediatric surgery

In the 50 years since the first edition of this journal, operative paediatric surgery has undergone radical change. Many of the most common instruments are unchanged, both as a testament to their utility and in recognition of past surgeons remembered eponymously. Surrounding that basic core of instruments, theatre has changed radically as new tools and techniques have arisen. Surgeons have come down from their pedestals, recognising surgery as a team sport rather than a solo performance. More than half of the current paediatric surgical trainees are women, a higher proportion than in any other craft group of the Royal Australasian College of Surgeons. The appearance, and rapid development, of laparoscopy is to many observers the most notable change in surgery over the last 50 years. Placed in its context though, it is simply the most prominent example of a frameshift in surgical thinking. The patient as a whole is now the focus, rather than just the disease. Recent developments are as much about minimising harm to normal tissues as they are about extirpating pathology. As a surgical maxim, ‘Primum non nocere’ is even more in evidence in 2015 than it was in 1965.     

Meta-analysis using individual patient data from randomised trials to assess the effectiveness of laparoscopic uterosacral nerve ablation in the treatment of chronic pelvic pain: a proposed protocol

Background  Currently, there are a number of clinical trials, but no international collaboration for collating research on effectiveness of laparoscopic uterosacral nerve ablation (LUNA) for alleviating chronic pelvic pain.
Objective  Meta-analysis was used by collecting individual patient data (IPD) from the existing trials, to provide a comprehensive assessment of the effectiveness of LUNA that will be generalisable in various clinical contexts.
Methods  IPD will be sought and collected from all relevant (both already finished and continuing) randomised trials identified through previous systematic reviews. After obtaining raw data and cleaning the database, analysis will be of all patients ever randomised based on the intention-to-treat principle using endpoints measured at 12 months following randomisation.
Proposal  We will update searches, contact all authors, obtain data in whatever form it can be provided, build a single database, produce results for individual studies, have them verified by original authors, explore of any heterogeneity and reasons behind it and finally pool all raw data in to a meta-analysis using appropriate statistical methods. The project will test the effectiveness of LUNA for women with chronic pelvic pain. It will also motivate collaborating primary investigators to undertake new primary studies to corroborate or improve upon the conclusions derived from the retrospective analysis.     

Serum CA19-9 measurement increases the effectiveness of staging laparoscopy in patients with suspected pancreatic malignancy

BACKGROUND/AIMS: Staging laparoscopy for suspected pancreatic neoplasia is not widely accepted due to its low yield. The aim of this study was to determine if serum carbohydrate antigen (CA19-9) levels could be used to improve the selection of patients for staging laparoscopy. METHODS: The data from a prospectively collected database (1997-2004) with 159 patients who had computed tomography-predicted resectable disease and who had undergone laparoscopic staging were analysed to determine if a low preoperative CA19-9 level (< or =150 kU/l, or < or =300 kU/l with a bilirubin >35 micromol/l) identified patients in whom laparoscopy was not useful. Results: The CA19-9 level was >150 kU/l in 96 patients of whom 75 (78%) were considered resectable following laparoscopic assessment. There were 63 patients with a CA19-9 < or =150 kU/l of whom 60 (95%) were considered resectable following laparoscopic assessment. The sensitivity, specificity, positive predictive value and negative predictive value for CA19-9 < or =150 kU/l in predicting that laparoscopic assessment would judge patients as resectable were 44, 88, 95 and 22%, respectively. A cut-off level of < or =300 kU/l in patients with a bilirubin >35 micromol/l produced values of 30, 94, 94 and 28%, respectively. By using CA19-9 < or =150 kU/l, laparoscopy could have been avoided in 40% of patients, increased to 55% of patients with adjustment for the presence of jaundice; concomitantly, the yield from laparoscopy would have been increased from 15 to 22 and 25%, respectively. Conclusion: Use of serum CA19-9 levels would increase the efficiency of laparoscopic staging in patients with suspected pancreatic malignancy.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.