Anne C. Fischer

Cannot exclude torsion—a 15-year review

BACKGROUND Ovarian torsion remains a challenging diagnosis, often leading to delayed operative intervention and resultant ovarian loss. METHODS Charts of patients with ovarian operative cases were retrospectively reviewed at a free-standing childrens hospital over 15 years. Torsion was based on intraoperative findings. RESULTS Of 328 operative ovarian cases, 97 (29.6%) demonstrated torsion. Mean patient age was 9.2 years (2 days to 17 years, +/-0.54 SEM), with 52% occurring between 9 and 14 years. Of the patients, 97% presented in pain. Presence of a pelvic mass 5 cm or larger on imaging had 83% sensitivity for torsion: an ultrasound reading was only 51% sensitive. Elevated white blood cell count was the only preoperative characteristic associated with prompt operative intervention. Utilization of laparoscopy increased during the latter half of the study (18%-42%, P < .0434). There was a positive trend, although insignificant, in the use of laparoscopy and ovarian salvage. Pathology was overwhelmingly benign (infarction [46%], cysts [33%], and benign neoplasms [19%]). CONCLUSION Torsion was responsible for one third of all operative ovarian cases. Sonography is not reliable in diagnosis or exclusion of ovarian torsion. Thus, a strategy of earlier and liberal use of Diagnostic Laparoscopy (DL), particularly with a pelvic mass of approximately 5 cm, may improve ovarian salvage. Because pathology is predominantly benign, the edematous detorsed ovary is safe to salvage.

Pediatric ovarian malignancy presenting as ovarian torsion: incidence and relevance.

PURPOSE With ovarian torsion, concern for underlying malignancy in the enlarged ovary has previously driven surgeons to resection. Detorsion alone has been recommended to allow for resolution of edema of the ovary with follow-up ultrasound surveillance to evaluate for a persistent mass, yet is not routine practice. However, the incidence of malignancies presenting as ovarian torsion is not documented. Does the risk of an underlying malignancy justify salpingoophorectomy and decreased fertility? METHOD After institutional review board exemption (IRB#-022008-095), a 15(1/2)-year retrospective review was conducted to identify cases of operative ovarian torsion in our medical center. Tumors with neoplastic pathology (malignant and benign) were analyzed and compared with all reported cases in the literature. RESULTS A total of 114 patients (mean +/- SEM age, 10 years, 2 days to 19 years +/- 0.53) with operatively proven ovarian torsion were identified. Four malignancies (3.5%) and 26 benign neoplasms (23%) were present in this age group. Malignancies consisted of serous borderline tumors (2), juvenile granulosa cell tumor (1), and dysgerminoma (1). All were stage I: the former were stage IA and cured with resection alone, and 1 was a stage IB dysgerminoma, which required chemotherapy. The literature yielded a total of 593 cases of operative ovarian torsion with 9 (1.5%) malignancies and 193 (33%) benign neoplasms. The malignancies were juvenile granulosa cell tumor (n = 4), dysgerminoma (n = 2), serous borderline tumors (n = 2), and 1 undifferentiated adenocarcinoma. CONCLUSION By combining our series with 13 in the literature, a 1.8% malignancy rate occurred in 707 patients with ovarian torsion, markedly less than the reported malignancy rate of 10% in children with ovarian masses. Thus, neither a pathologic nor malignant lead point should be assumed in cases of torsion. In our series, which represents the largest series of torsion in the pediatric literature, all malignancies presented as stage I. These data further support the implementation of operative detorsion and close postoperative ovarian surveillance, with reoperation for persistent masses. Further study is needed to determine if delaying resection by weeks in those cases of persistent masses would result in tumor progression and thus change prognosis.

Can we preoperatively risk stratify ovarian masses for malignancy

PURPOSE Given a 10% malignancy rate in pediatric ovarian masses, what preoperative factors are helpful in distinguishing those at higher risk to risk stratify accordingly? METHODS After institutional review board approval (IRB#022008-095), a 15(1/2)-year retrospective review of operative ovarian cases was performed. RESULTS A total of 424 patients were identified, with a mean age 12.5 years (range, 1 day to 19 years), without an age disparity between benign (12.54 years, 89%) and malignant (11.8 years, 11%) cases. The 1- to 8-year age group had the highest percentage of malignancies (22%; odds ratio [OR], 3.02; 95% confidence interval [CI], 1.33-6.86). A chief complaint of mass or precocious puberty versus one of pain had an OR for malignancy of 4.84 and 5.67, respectively (95% CI, 2.48-9.45 and 1.60-20.30). Imaging of benign neoplasms had a mean size of 8 cm (range, 0.9-36 cm) compared with malignancies at 17.3 cm (6.2-50 cm, P < .001). An ovarian mass size of 8 cm or longer on preoperative imaging had an OR of 19.0 for malignancy (95% CI, 4.42-81.69). Ultrasound or computed tomographic findings of a solid mass, although infrequent, were most commonly associated with malignancy (33%-60%), compared with reads of heterogeneous (15%-21%) or cystic (4%-5%) lesions. The malignancies (n = 46) included germ cell (50%, n = 23), stromal (28%, n = 13), epithelial (17%, n = 8), and other (4%, n = 2). Tumor markers obtained in 71% of malignancies were elevated in only 54%, whereas 6.5% of those sent in benign cases were similarly elevated. Elevated beta-human chorionic gonadotropin (beta-HCG), alpha fetoprotein (alphaFP), and cancer antigen 125 (CA-125) were significantly associated with malignancy (P < .02) and an elevated carcinoembryonic antigen (CEA) was not (P = .1880). CONCLUSION This reported series of pediatric ovarian masses demonstrates that preoperative indicators that best predict an ovarian malignancy are a complaint of a mass or precocious puberty, a mass exceeding 8 cm or a mass with solid imaging characteristics. Those patients aged 1 to 8 years have the greatest incidence of malignancy. Tumor markers, positive or negative, were not conclusive in all cases but useful for postoperative surveillance.

The use of artificial dermis in the reconstruction of oncologic surgical defects.

Background: Integra dermal substitute has been used in burn reconstruction with great success. Its use in general reconstruction is currently being reported. The authors set out to evaluate the utility of Integra in the reconstruction and resurfacing of defects created by tumor excision. Methods: Since 2003, 17 patients with soft-tissue tumors involving the head and neck, lower extremity, and anterior chest wall underwent tumor resection and reconstruction with Integra dermal substitute. These patients were followed and clinical outcomes were assessed. Results: Seventeen patients with a mean age of 54 ± 21 years underwent tumor resection and reconstruction with Integra dermal substitute. Twelve patients (71 percent) were male and five (29 percent) were female. Twelve cases (71 percent) involved recurrent tumor resection. The 17 cases involved 10 different tumor types at six different anatomical locations. The mean defect size was 172 ± 260 cm2 (range, 20 to 1080 cm2). The second stage of the reconstruction occurred on postoperative day 23 ± 6. The mean follow-up was 12.3 ± 7.2 months (range, 3 to 26 months). Clinically, 16 patients had 100 percent take of skin grafts and one patient had approximately 97 percent take of his graft. All patients experienced excellent defect contouring and cosmesis. Conclusions: Artificial bilaminate acellular dermis is an excellent option for reconstructing defects created by tumor resection and can be used in a wide variety of locations. It is especially useful in large defects that usually require flaps for coverage. Patients experience minimal donor-site morbidity and have outstanding cosmetic and functional results.

A Population-Based Analysis of 1037 Malignant Ovarian Tumors in the Pediatric Population

BACKGROUND Concerns of malignant potential have impacted the utilization of ovarian salvage for treatment of ovarian masses in children. METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was analyzed for all females < or =19 y diagnosed with an ovarian tumor between 1973 and 2005. RESULTS Overall, 1037 pediatric patients with ovarian tumors were identified. Approximately 61.7% of tumors occurred in patients 15 to 19 y old. The age-adjusted incidence of all malignant pediatric ovarian tumors in those < or =9 y was 0.102 versus 1.072 per 100,000 in those aged 10 to 19 y. The majority of cases (57.4%) present at an early localized stage. The predominant pathology was germ cell tumors in all age groups (77.4%). Overall 5- and 10-y survival rates are 91.7% and 91.4%, respectively. By multivariate analysis, advanced disease stage (HR 3.17, P<0.001), lack of surgery (HR 4.49, P =0.039), and poorly differentiated tumors (HR 3.40, P=0.011) were associated with worse outcomes. CONCLUSIONS Malignant ovarian tumors are rare, particularly in patients under 5 y of age. Furthermore, the most common histologies are of low metastatic potential and carry high cure rates. Thus, the surgeon should implement ovarian-sparing strategies on the affected ovary unless a malignancy is clearly suspected and conserve the contralateral ovary in all children.

Malignant breast cancer in children: a review of 75 patients.

OBJECTIVE To determine incidence trends and outcomes for pediatric patients with malignant breast disease. METHODS The Surveillance, Epidemiology, and End Results registry was examined for all females 19 years of age and younger diagnosed with a malignant breast tumor between 1973 and 2004. RESULTS A total of 75 patients with malignant breast tumors were identified. Overall, 14.5% of patients had in situ tumors, and 85.5% had invasive disease. Tumors were classified as being either carcinomas (n = 41, 54.7%) or sarcomas (n = 34, 45.3%). The majority of sarcomatous lesions were phyllodes tumors (n = 29, 85.5%), whereas most carcinomas were of a ductal etiology (n = 19, 46.3%). The age-adjusted incidence of all malignant pediatric breast tumors in 2003 was 0.08 cases per 100,000 people (0.03 carcinoma and 0.06 sarcoma cases per 100,000 people). In the carcinoma group, regionally advanced disease was present in 11 patients (26.8%), whereas only 3 patients (7.3%) presented with metastatic disease. All patients with sarcomatous tumors presented with localized disease. Adjuvant radiation therapy was administered in only 9.8% of carcinomas and 8.8% of sarcomas, and 85.4% of carcinoma patients and 97.1% of sarcoma patients underwent surgical resection for their primary disease. Subgroup analysis revealed 5- and 10-year survival rates of 89.6% for patients with sarcomatous tumors and 63.1% and 54.3% for carcinomas. CONCLUSIONS Malignant pediatric breast malignancies remain relatively rare. The two most common histologies of breast neoplasms in children are malignant carcinomas followed by sarcomas. Although uncommon, malignant disease must be considered in the differential diagnosis of the pediatric patient with a breast mass.

Single-incision laparoscopic surgery: feasibility for pediatric appendectomies

INTRODUCTION Single-incision laparoscopic surgery (SILS) is a novel area of minimally invasive surgery using a single incision. The end result is a lone incision at the umbilicus for a perceived scarless abdomen. We report our early experience using the SILS technique for appendectomies in the pediatric population. METHODS A retrospective chart review was performed on our first patients to undergo SILS appendectomy (SILS-A) or laparoscopic appendectomy (LAP-A) during the same period at a freestanding childrens hospital. RESULTS Thirty-nine patients were reviewed. Nineteen patients underwent SILS-A (8.7 +/- 0.76 [SEM] years old), and 20 patients underwent LAP-A (10.5 +/- 0.87 years old, 2-17). Ages were 19 months to 14 years in the SILS-A group, with 21% (4 patients) not older than 6 years. Median weight for SILS-A was 32 kg (14.5-80.3). Twelve patients had acute nonperforated appendicitis (62%). Mean duration of operation was 58 +/- 5.6 (30-135) minutes vs 43 +/- 3.6 (30-85) minutes for standard LAP-A. Two patients were converted to a transumbilical appendectomy, one for inability to maintain a pneumoperitoneum and one for extensive adhesions. Postoperative complications consisted of one wound seroma. No wound infections, hernias, readmissions, or difference in length of stay were noted. CONCLUSION The SILS approach for acute appendicitis is feasible in the pediatric population even in patients as young as 19 months. Operating room times are somewhat longer than with LAP-A, but should decrease with improved instrumentation and experience. Larger studies and further technical refinements are needed before its widespread implementation.

Dual Reporter Comparative Indexing of rAAV Pseudotyped Vectors in Chimpanzee Airway

Selecting the most efficient recombinant adeno-associated virus (rAAV) serotype for airway gene therapy has been difficult due to cross-specific differences in tropism and immune response between humans and animal models. Chimpanzees--the closest surviving genetic relative of humans--provide a valuable opportunity to select the most effective serotypes for clinical trials in humans. However, designing informative experiments using this protected species is challenging due to limited availability and experimental regulations. We have developed a method using Renilla luciferase (RL) and firefly luciferase (FL) reporters to directly index the relative transduction and immune response of two promising rAAV serotypes following lung coinfection. Analysis of differential luciferase activity in chimpanzee airway brushings demonstrated a 20-fold higher efficiency for rAAV1 over rAAV5 at 90 days, a finding that was similar in polarized human airway epithelia. T-cell responses to AAV5 capsid were stronger than AAV1 capsid. This dual vector indexing approach may be useful in selecting lead vector serotypes for clinical gene therapy and suggests rAAV1 is preferred for cystic fibrosis.

Pediatric Solid Tumors and Second Malignancies: Characteristics and Survival Outcomes

BACKGROUND To examine the incidence, characteristics, and outcomes for second malignancies following the diagnosis of a primary solid tumor in pediatric patients. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1973 to 2005, excluding recurrences, in patients <20 y. RESULTS A total of 31,685 cases of pediatric solid malignancies were identified. Overall, 177 patients were diagnosed with a unique second malignancy before the age 20 (0.56%) The mean follow-up was for 8.5 y (2 mo-30.8 y). Mean age at diagnosis of the primary tumor was 7.7 y. The most common primary malignancies were CNS tumors (22.5%), followed by soft tissue sarcoma (15.8%), retinoblastoma (14.1%), and bone tumors (13%). Hematologic malignancies (35.5%) were the most common second malignancies noted in the cohort, followed by bone tumors (18%) and soft tissue sarcomas (15%). Hematologic malignancies had a shorter latency (3.1 y) compared with solid second tumors (11.6 y). The overall 10-y survival for the entire cohort was 41.5%. For most tumor categories, development of a secondary malignancy was associated with lower 5- and 10-y survival than expected. CONCLUSIONS CNS tumors, retinoblastoma, and soft tissue sarcomas in children are the most common solid primary tumors, with an increased risk of a second malignancy. Leukemia is the most common second malignancy seen in pediatric solid tumors. Second malignancies are associated with significantly reduced survival rates compared with the general childhood cancer population.

Cyclosporine-induced pseudo-graft-versus-host disease in the early post-cyclosporine period

Cyclosporine‐induced pseudo‐graft‐versus‐host disease (CIPGVHD) in syngeneic or autologous rat marrow chimeras has clinical and histologic features closely resembling classic graft‐versus‐host disease in the allogeneic chimera. We describe here the pathology and immunopathology of the usual target tissues in CIPGVHD developing in the first week following CsA (early group). The findings are contrasted to the CIPGVHD developing during the second week post‐CsA (later group). Six of 9 rats in the early group had acute‐type CIPGVHD in the tongue, skin, liver, intestines, and mainstem bronchi. In general, the lymphocytic infiltrates in these tissues were in intimate contact with injured epithelial cells. The intestines had multiple apoptotic lesions. Class II antigen was prominent in the tongue mucosa, but only patchy expression was evident in 2 skin biopsies. All of the lymphocytes infiltrating the mucosa were CD8+(OX‐8)/CD4‐(W3/25) T cells (OX‐19+). Most of the lymphocytes in the lamina propria expressed CD4 as well as CD8 markers, suggesting coexpression. In the later group, 6 of 7 rats had chronic‐type CIPGVHD (1 with acute and chronic) while 1 rat had no GVHD (P=.02, Fishers exact test compared with the early group). These animals had features characteristic of established chronic GVHD in the skin, tongue, liver, intestines, and salivary glands. Fibrosis of the dermis and lamina propria was prominent in the skin and tongue. Submucosal fibrosis was increased in the small intestine. The salivary glands had an interstitial infiltrate and fibrosis with loss of ducts and glands. Class II antigen was prominent in the epidermis of the tongue and skin of all rats. The number of lymphocytes infiltrating the mucosa of the tongue was considerably smaller than seen in the early group. More than 90% of these cells were T cells, as detected by OX‐19, and expressed both CD4 and CD8 markers. While most lamina propria lymphocytes expressed the CD4 antigen, there were significantly fewer CD8+ cells, consistent with increased numbers of CD8‐/CD4+ helper‐phenotype cells. The observations indicate that immediately post‐CsA, the CIPGVHD is primarily acute, with epithelial infiltrates of CD8+/CD4‐ T cells and lamina propria infiltrates that include double‐labeled cells consistent with immature thymocytes. There is a rapid transition to established chronic‐type CIPGVHD by the second week. The residual mucosal infiltrate is now dominated by double‐labeled T cells or thymocytes while the lamina propria infiltrate has more mature helper‐phenotype T cells. Induced RT1.B/D antigen could be important in the pathogenesis of the peripheral tissue manifestations.