Two-year experience with minimally invasive herniorrhaphy in children.

BACKGROUND: Laparoscopic herniorrhaphy in pediatrics is rarely performed. We evaluated our 2-year experience of minimally invasive inguinal herniorrhaphy in children. METHODS: All procedures were performed under general anesthesia using <2-mm instruments and scopes and a surgical awl to accomplish high ligation of the hernia sac under direct vision. RESULTS: A total of 90 consecutive children (76 males and 14 females) older than the age of 6 months underwent a minimally invasive herniorrhaphy (60 unilateral and 30 bilateral; total of 120 hernias repaired). Seventeen children underwent herniorrhaphy in conjunction with another procedure. All children who underwent herniorrhaphy alone were discharged immediately and allowed unrestricted activity. Only four patients requested a narcotic analgesic. There was one recurrence early in the series (0.83%), prompting a change in technique. CONCLUSIONS: Minimally invasive inguinal herniorrhaphy in children is a safe alternative for the experienced pediatric laparoscopist. There is a similar recurrence rate as that of the traditional open approach with a superior cosmetic result.

Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice.

Inhibition of tumor-induced neovascularization appears to be an effective anticancer approach, although long-term angiogenesis inhibition may be required. An alternative to chronic drug administration is a gene therapy-mediated approach in which long-term in vivo protein expression is established. We have tested this approach by modifying murine bone marrow-derived cells with a gene encoding an angiogenesis inhibitor: a soluble, truncated form of the vascular endothelial growth factor receptor-2, fetal liver kinase-1 (Flk-1). Murine bone marrow cells were transduced with a retroviral vector encoding either truncated, soluble Flk-1 (tsFlk-1) together with green fluorescent protein (GFP) or GFP alone. Tumor growth in mice challenged 3 months after transplantation with tsFlk-1-expressing bone marrow cells was significantly inhibited when compared with tumor growth in control-transplanted mice. Immunohistochemical analysis of tumors in each group demonstrated colocalization of GFP expression in cells staining with endothelial cell markers, suggesting that the endothelial cells of the tumor-induced neovasculature were derived, at least in part, from bone marrow precursors. These results suggest that long-term expression of a functional angiogenesis inhibitor can be generated through gene-modified, bone marrow-derived stem cells, and that this approach can have significant anticancer efficacy. Modifying these cells seems to have the added potential benefit of targeting transgene expression to the tumor neovasculature, because bone marrow-derived endothelial cell precursors seem to be recruited in the process of tumor-induced angiogenesis.

Autocrine expression of both endostatin and green fluorescent protein provides a synergistic antitumor effect in a murine neuroblastoma model.

Modalities that act through different mechanisms can often provide synergistic antitumor activity for the treatment of refractory tumors when used in combination. Here we report a gene therapy approach in which the genes for the angiogenesis inhibitor, endostatin, and the marker protein and potent immunogen, green fluorescent protein (GFP), were delivered to murine neuroblastoma cells prior to inoculation of the tumor cells into syngeneic immunocompetent mice. Although the effect of either angiogenesis inhibition or immunomodulation alone resulted in only a modest delay in tumor growth, when these approaches were used in combination, prevention of the formation of appreciable tumors was effected in 15 of 24 (63%) mice. The combination of endostatin and GFP expression elicited a strong immune response that was T cell-mediated and was reactive against both GFP and tumor cell line-specific antigens. This afforded treated mice protection against subsequent tumor challenge with unmodified tumor cells. These results suggest that antiangiogenic and immunotherapy strategies, when used in a gene therapy-mediated approach, can act synergistically in an effective multimodality anticancer approach.

The impact of margin of resection on outcome in pediatric nonrhabdomyosarcoma soft tissue sarcoma.

BACKGROUND/PURPOSE: Because the management of pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) is determined by extrapolation from adult studies, the effect of margin of tumor resection and postoperative radiation therapy (RT) on local tumor recurrence in children has not been assessed. METHODS: Records of NRSTS patients from a single institution were reviewed with regard to demographic data, TNM staging, grade, histological type and site of primary tumor, RT, and local tumor recurrence. The margin of resection was determined by pathological review and did not necessarily reflect operative margins. RESULTS: Eighty-eight clinical group I patients were treated over a 30-year period. The most common histological tumor subtypes were synovial cell sarcoma (n = 26), malignant fibrous histiocytoma (n = 17), and fibrosarcoma (n = 7). The mean age was 9.4 years (range, 0 to 29 years). Thirty-four patients had high-grade tumors. Two of ten patients with low-grade tumors and margins less than 1 cm, including one of five who had received RT, had a local recurrence. Patients with low-grade tumors and margins greater than 1 cm (n = 44) had a lower recurrence rate (2 of 44, 4.5%). None of these patients had received RT. Fourteen patients with high-grade tumors had margins less than 1 cm. Seven of these had RT and had no recurrence. Three of the seven patients who received no RT had a recurrence (42.9%). None of the 20 patients with high-grade tumors and margins greater than 1 cm received RT; four of these patients had recurrences (20%). Seven of the 12 irradiated patients (58.3%) had serious radiation-associated complications (wound dehiscence, fracture, growth retardation, and joint dysfunction). CONCLUSIONS: Grade alone does not determine the rate of local recurrence. In both low- and high-grade tumors, a pathological margin of resection greater than 1 cm reduced local recurrence. Radiotherapy provided no advantage in low grade tumors but did decrease local recurrence rates in high-grade tumors with less than 1 cm pathological margins.

Resection of foregut-derived duplications by minimal-access surgery.

Eight children underwent minimal-access surgery (MAS) for duplications of foregut derivatives. The efficacy and safety of this approach are reviewed. The seven patients with mediastinal lesions had video-assisted thoracoscopic resection. One lesion presented as a subdiaphragmatic esophageal diverticulum, which was excised laparoscopically. Between March 1991 and October 1997, eight children were treated. Mean age was 27 months and mean weight was 11. 4 kg. Mean operating time was 106 min, and mean postoperative hospital stay was 4.5 days (median = 2 days). Persistent air leaks occurred in two patients who had centrally-located bronchogenic cysts. One of these, who had undergone subtotal excision with laser photoablation of the remaining cyst mucosa, developed a recurrence that was excised at thoracotomy. We conclude that esophageal and bronchogenic cysts and duplications may be safely excised by MAS in children, with excellent cosmetic and functional outcome. Two technical points are noted: (1) a thoracostomy tube is required for central mediastinal lesions; and (2) complete excision is required to prevent recurrence.

Current status of laparoscopic appendectomy in children.

Appendectomy is the most common surgical emergency in children. Laparoscopic appendectomy (LA), first performed by Semm in 1983, has increased in popularity for both uncomplicated and ruptured appendicitis. The authors perform early laparoscopic appendectomy for acute uncomplicated appendicitis, but use aggressive antibiotic therapy for obvious ruptured appendicitis. Patients presenting with accessible abscesses have drainage using image guidance. Antibiotic therapy is continued at home until the fever has resolved and the white blood cell and differential counts have normalized. An interval appendectomy is performed 2 to 3 months later. Children with ruptured appendicitis for whom aggressive medical management had failed usually had a persistent pattern of small bowel obstruction noted 72 hours after initiation of treatment. The authors' preferred technique for laparoscopic appendectomy employs linear stapling of the mesoappendix and appendix. LA patients had a shorter hospital stay and a lower wound infection rate. The operating times for open and laparoscopic appendectomy were similar.

Current status of laparoscopic appendectomy in children.

Acute appendicitis is the most common surgical emergency in children. Open appendectomy has been the standard treatment for decades, with excellent results. Owing to advances in pediatric laparoscopic instrumentation and increased experience with the technique of laparoscopy, however, many centers are routinely performing laparoscopic appendectomy in children. Most studies show a marginal advantage of laparoscopic appendectomy over open appendectomy with regard to length of hospitalization, postoperative analgesia use, length of time until return to full activity, and wound infection rate. There is a wide range of clinical presentation in children with acute appendicitis, from mild inflammation of the appendix to ruptured appendicitis with diffuse peritonitis or localized abscess formation. Patients with ruptured appendicitis have many more complications regardless of the surgical approach. Prospective, randomized studies specifically in children are needed to answer remaining questions regarding any potential benefit of laparoscopic appendectomy and for which patients this technique is best suited.

Laparoscopic appendectomy in children.

Laparoscopic appendectomy is a common surgery in most pediatric surgical centers. Many studies, mostly retrospective reviews in adults, show the advantages of the laparoscopic approach to be less wound infections, shortened postoperative recovery, and faster return to normal activities. In addition, less analgesic medication is required postoperatively. Potential disadvantages of laparoscopic appendectomy include an increased operative time, elevated costs when disposable instruments are used, and possibly more infectious complications when performed for complicated appendicitis. There are no prospective, randomized trials comparing laparoscopic versus open appendectomy in children. Until these studies are completed, questions will persist regarding the benefits of laparoscopic appendectomy in children.