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Biomedical subjects

Carl-Christian A Jackson

Publications and source records attributed to Carl-Christian A Jackson.

7 recordsLinked to original sources

CD40 ligation restores cytolytic T lymphocyte response and eliminates fibrosarcoma in the peritoneum of mice lacking CD4+ T cells.

Absence of CD4(+) T cell help has been suggested as a mechanism for failed anti-tumor cytotoxic T lymphocytes (CTL) response. We examined the requirement for CD4(+) T cells to eliminate an immunogenic murine fibrosarcoma (6132A) inoculated into the peritoneal cavity. Immunocompetent C3H mice eliminated both single and repeat intraperitoneal (IP) inoculums, and developed high frequency of 6132A-specific interferon-gamma (IFNgamma)-producing CTL in the peritoneal cavity. Adoptive transfer of peritoneal exudate cells (PEC) isolated from control mice, protected SCID mice from challenge with 6132A. In contrast, CD4 depleted mice had diminished ability to eliminate tumor and succumbed to repeat IP challenges. Mice depleted of CD4(+) T cells lacked tumor-specific IFNgamma producing CTL in the peritoneal cavity. Adoptive transfer of PEC from CD4 depleted mice failed to protect SCID mice from 6132A. However, splenocytes isolated from same CD4 depleted mice prevented tumor growth in SCID mice, suggesting that 6132A-specific CTL response was generated, but was not sustained in the peritoneum. Treating CD4 depleted mice with agonist anti-CD40 antibody, starting on days 3 or 8 after initiating tumor challenge, led to persistence of 6132A-specific IFNgamma producing CTL in the peritoneum, and eliminated 6132A tumor. The findings suggest that CTL can be activated in the absence of CD4(+) T cells, but CD4(+) T cells are required for a persistent CTL response at the tumor site. Exogenous stimulation through CD40 can restore tumor-specific CTL activity to the peritoneum and promote tumor clearance in the absence of CD4(+) T cells.

Adoptive Transfer↗

Cost considerations and applicant characteristics for the Pediatric Surgery Match.

BACKGROUND/PURPOSE: Formal training in pediatric surgery is highly competitive. The limited number of accredited positions has historically favored applicants with basic science experience, numerous publications, national presentations, and exposure to well-known pediatric surgeons. This review analyzes characteristics of successful applicants and cost associated with the Match. METHODS: A survey was e-mailed to 45 applicants after the 2003 Match. Geographic provenance, demographics, qualifications, costs, and valued program characteristics were assessed. Statistics were formulated by chi2 and Student's t test. RESULTS: Thirty-six applicants (80%) responded. Successful characteristics for matched vs unmatched included number of publications, 11.2 vs 5.7 (P < .01); first-author designation, 6.4 vs 3.1 (P = .02); basic science papers, 5.7 vs 1.7 (P < .01); national presentations, 5.8 vs 2.4 (P = .02); and presentations at pediatric surgical meetings, 2.0 vs 0.6 (P = .04). Ninety percent of matched applicants took time off to perform basic science research (P < .01). Average candidate expense was $6974, which represented 14% of pretax salary. Forty-one percent of applicants noted that cost limited the number of interviews taken. Fifty percent preferred a regional interview process to limit expense. Candidates ranked case diversity, volume, and mentor's advice as the most valued program characteristics. Successful applicants matched at their fifth rank on average. Eighty-six percent of unsuccessful applicants will reapply. CONCLUSIONS: Results of this study are important to those interested in the future of pediatric surgery. Successful applicants were shown to have several national presentations and multiple scientific publications, especially in basic sciences. Applicant costs are high, totaling more than $236,000 for survey respondents.

Adult↗

Stretta as the initial antireflux procedure in children.

BACKGROUND: The Stretta procedure is an endoluminal antireflux procedure using radio frequency to induce collagen tissue contraction, remodeling, and modulation of lower esophageal sphincter physiology in an effort to treat gastroesophageal reflux disease (GERD). Although Stretta has been widely reported in the adult GERD literature as a viable initial surgical option, similar use in children has not been reported. The authors present the first report of Stretta as the initial antireflux procedure in children with GERD, evaluating indications, safety, and efficacy. METHOD: The charts of 8 children (aged 11-16 years) who received Stretta between January 2003 and September 2003 were retrospectively reviewed under an Institutional Review Board protocol. All patients had documented GERD preoperatively. Three children required concomitant feeding tube placement (percutaneous gastrostomy tube, group A). Five children with isolated severe GERD refractory to aggressive medical therapy received Stretta only (group B). RESULTS: Stretta was successfully completed in all 8 children. In group A, 1 child developed a postoperative aspiration, which was successfully treated. All 3 children had resolution of their GERD symptoms (ie, feeding intolerance, emesis) and were able to tolerate full enteral nutrition post-Stretta. In group B, 3 of 5 children are currently off medications and asymptomatic on short-term follow-up (6-15 months). Of the remaining 2, 1 experienced symptomatic relief immediately postprocedure, but symptoms recurred off medications. Stretta was deemed unsuccessful in the remaining patient, and Nissen fundoplication was subsequently performed without difficulty. CONCLUSIONS: Stretta can be safely and successfully used as the initial antireflux procedure for children with GERD. Concomitant Stretta with PEG is an attractive option in children with preexisting GERD who require long-term feeding access. Longer follow-up and a larger patient population are needed to better confirm the safety and efficacy of Stretta presented in this report.

Adolescent↗

Surgical therapy for Barrett's esophagus.

Given the anatomic and functional defects almost universally present in patients who have BE, antireflux surgery is the most reliable means of stopping acid and nonacid (alkaline) reflux. Because patients who have BE have end-stage GERD, they require durable and reliable control of reflux, and the Hill procedure and partial fundoplication are associated with unacceptably high failure rates. In addition, there is mounting evidence that the success rates for Nissen fundoplication are lower in patients who have BE than in patients who have less severe GERD. Given that the most common mode of failure of a laparoscopic Nissen fundoplication is herniation of the fundoplication into the chest, patients who have BE must be considered at risk for having a short esophagus. The failure rate may be reduced by the liberal addition of a Collis gastroplasty, but the long-term consequences of acid-secreting mucosa left above the fundoplication in patients who have BE remain unclear. Patients suspected of having a short esophagus on the basis of a large hiatal hernia, stricture, or long-segment BE should be considered for a transthoracic approach to their fundoplication, as this affords good esophageal mobilization and may obviate the need for a gastroplasty. Surgeons must pay particular attention to their own and published results and continue to refine the operation to maximize the likelihood of a good outcome in this difficult group of patients. It is only with excellent control of reflux that any differences in the risk of progression to dysplasia and cancer become apparent, and significant, between medically and surgically treated patients.

Barrett Esophagus↗

Minimally invasive surgery for pediatric solid neoplasms.

The role of minimally invasive surgery (MIS) in children with solid neoplasms is slowly evolving. MIS appears to be an ideal way to obtain diagnostic information (i.e., tissue biopsy) in children with solid neoplasms, but its role as an ablative/curative technique is controversial. We examined the safety, reliability, and outcome of decisions made on the basis of MIS performed in children with solid neoplasms. A total of 28 children (19 boys and nine girls; age range, 14 months to 17 years) with solid neoplasms underwent 29 MIS procedures between July 1, 2000 and June 30, 2002. Complications, biopsy results, and outcomes were reviewed. Successful ablation via MIS was defined as clear microscopic margins on permanent pathology and no evidence of remnant disease on follow-up diagnostic radiological examination. There were 20 thoracoscopic and nine laparoscopic procedures. Laparoscopy included purely diagnostic without tissue biopsy or simply determination of resectability (two), incisional biopsy (two), and excisional biopsy (five; two adrenalectomy and three oophorectomy). Thoracoscopy included 15 lung biopsies and five biopsies of mediastinal masses. Diagnostic accuracy was 100 per cent in all cases. MIS as an ablative technique was successful in 10 of 10 cases. No children were found retrospectively to have been inadequately treated via MIS. We conclude that MIS can be used safely and successfully to diagnose children with suspicious solid neoplasms. Furthermore MIS may have a role as an ablative/curative technique in carefully selected circumstances.

Adolescent↗

Thoracoscopic thymectomy in children with myasthenia gravis.

Although conservative medical management is the mainstay in the treatment of myasthenia gravis (MG), severest forms of the disease often require surgical thymectomy. Thoracoscopic thymectomy (TT) represents a minimally invasive alternative to traditional thymectomy via sternotomy. We present our preliminary experience with TT as definitive treatment for severe forms of MG. The charts of 5 children (4 girls and 1 boy; age range, 11-17 years) who underwent TT for MG were retrospectively reviewed. TT was typically performed via left thoracoscopy using 4- or 5-mm ports with 1 of the ports enlarged at the end of the procedure for specimen retrieval. Thymic veins were identified and ligated with surgical clips in all cases. Surgical parameters assessed were the following: operating time, intra- and postoperative complications, length of postoperative stay, and resolution of symptoms. Follow-up ranged from 6 months to 2 years. All 5 TTs were successfully completed. In 1 case, right-sided thoracoscopy was added to ensure complete gland excision. Surgical pathology in all cases demonstrated complete excision. Mean operating time was 121 minutes (range 88 minutes to 188 minutes). There were no intra- or postoperative complications. Length of postoperative stay averaged 1.6 days (range, 1 to 3 days). Four of 5 (80%) had clear resolution of symptoms with 1 showing minimal resolution at 6 months. Thoracoscopic thymectomy is a safe and potentially attractive alternative to traditional thymectomy via median sternotomy in severe forms of myasthenia gravis. Complete thymectomy, the goal of traditional surgical treatment for myasthenia gravis, can effectively by achieved via this minimally invasive technique.

Adolescent↗

Bile decompression in children with histopathological evidence of pre-existing liver cirrhosis.

Although it is agreed upon by most that adequate and timely bile decompression can preserve or even improve existing liver function much debate centers on whether pre-existing liver cirrhosis can also be reversed. To help answer this question we analyzed data on 47 children with choledochal cyst disease (CD) who underwent simultaneous liver biopsy during bile decompression surgery. We collected data on two groups of children with CD spanning two different time periods: January 1985 through November 1994 (Group A) and June 1995 through November 1999 (Group B). In Group A 37 children (16 boys and 21 girls ages 5 days to 10 years) underwent simultaneous liver biopsy during elective definitive surgery for CD. In Group B ten children (five boys and five girls age one month to 7 years) underwent liver biopsy twice: first during initial cyst decompression for acute obstruction and second during elective definitive surgery after resolution of acute disease. Degree of liver cirrhosis was based on a modified World Health Organization classification system (0-IV). In Group A 15/37 (40.5%) had significant liver cirrhosis at time of biopsy (III or IV) with altered liver function in all cases; eight of nine had normal liver function on follow-up, six were lost to follow-up. In Group B seven of ten (70%) had less liver cirrhosis on pathology at second operation with three unchanged; nine of ten (90%) regained normal liver function. We conclude that bile duct obstruction is the main cause of liver cirrhosis in children with CD. Adequate and timely bile decompression can restore normal liver function and even reverse severe cirrhosis.

Biopsy↗