Barrie S. Rich

Risk Factors and Predictors of Severity Score and Complications of Pediatric Hemorrhagic Cystitis

PURPOSE We retrospectively analyzed our institutional incidence of hemorrhagic cystitis, identified risk factors, and examined associations of risk factors with disease severity and genitourinary complication rates. MATERIALS AND METHODS We reviewed charts of all consecutive pediatric patients treated from 1986 to 2010. We analyzed demographics, underlying diagnosis and treatment data to assess risk factors for hemorrhagic cystitis. We also correlated disease severity scores with clinical predisposing factors, and performed univariate and multivariate analyses to examine associations between risk factors and outcomes. RESULTS Hemorrhagic cystitis was observed in 97 of 6,119 children (1.6%), most of whom (75%) had severity scores of II or III. Mean ± SD age was 12.2 ± 6.3 years for patients with hemorrhagic cystitis and 10.5 ± 7 years for patients without hemorrhagic cystitis (p = 0.017). On univariate analysis increased risk of hemorrhagic cystitis was significantly associated with age greater than 5 years, male gender, cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy and underlying diagnoses of rhabdomyosarcoma, acute leukemia and aplastic anemia. On multivariate analysis age greater than 5 years, allogeneic bone marrow or peripheral blood stem cell transplantation and pelvic radiotherapy were significantly associated with increased risk of hemorrhagic cystitis. Older age, late onset hemorrhagic cystitis, positive urine culture for BK virus and bone marrow or peripheral blood stem cell transplantation were associated with greater disease severity. Patients with higher severity scores more frequently experienced bladder perforation, hydronephrosis, overall hemorrhagic cystitis complications, and increased creatinine and blood urea nitrogen levels during followup. CONCLUSIONS Older age, previous bone marrow or peripheral blood stem cell transplantation and BK virus in the urine are risk factors for hemorrhagic cystitis and are associated with a higher severity score. Higher severity scores are associated with increased rates of genitourinary complications and renal impairment.

Resectability and operative morbidity after chemotherapy in neuroblastoma patients with encasement of major visceral arteries

BACKGROUND/PURPOSE Image-defined vessel encasement is a significant risk factor for surgical complications and incomplete resection for intermediate-risk tumors. We sought to examine the impact of vessel encasement on complications or resectability in intermediate-risk or high-risk patients after neoadjuvant chemotherapy. METHODS We retrospectively reviewed 207 consecutive patients with circumferential encasement of the renal vessels, celiac axis, and/or superior mesenteric artery (SMA) who underwent resection between 1991 and 2009. Specifically, we evaluated resection rates, complications, and outcome. RESULTS Median age at diagnosis was 3.0 years, and 79% of patients had stage 4 disease. Of known MYCN status, 23.4% had MYCN amplification. Vessel encasement included renal vessels, celiac axis, or SMA alone in 107, 7, and 4 patients, respectively. Both the renal vessels and celiac axis were encased in 5 patients, renal vessels and SMA in 7 patients, and celiac axis and SMA in 14 patients. Sixty-three patients had all 3 vessels encased. The gross total resection (GTR) rate was 94%. No operative or postoperative deaths occurred. The overall complication rate was 34.8% (n = 72). Overall 5-year survival (± SEM) was 67.4% (± 7.4%). CONCLUSION Encasement of major visceral arteries in patients with neuroblastoma who have received chemotherapy does not preclude gross total resection.

Acinar cell cystadenoma of the pancreas in a 9-year-old boy

This report describes a rare benign cystic lesion of the pancreas known as acinar cell cystadenoma. There are 12 previously reported cases, the youngest patient from which was age 16. We report the youngest case to date, occurring in a 9-year-old boy. The pancreatic lesion was found incidentally and confirmed by laparoscopic biopsy. A pseudocyst formed, which was drained endoscopically. Given that the lesion was benign and the patient was asymptomatic, no further intervention was recommended. Complete resection would require a total pancreatectomy, with attendant morbidity, and review of the literature suggests a benign course. In asymptomatic cases, we recommend biopsy for histologic diagnosis, with close follow-up and without further surgical intervention.

Factors associated with relapse and survival in Wilms tumor: a multivariate analysis

PURPOSE Lymph node metastasis and anaplasia predict relapse-free survival in Wilms tumor. We performed a multivariate analysis of our institutional database to identify factors independently associated with relapse-free and overall survival. METHODS We retrospectively reviewed cases of confirmed Wilms tumor diagnosed between 1990 and 2010 and treated at our institution. The log-rank test was used to screen variables for consideration in the proportional hazards model. RESULTS A total of 95 patients were treated at our institution during the study period, with a median follow-up of 3.3 years. Factors correlated with overall survival in the univariate analysis were local disease, metastasis, tumor size, anaplasia, renal vein tumor thrombus, inferior vena cava tumor thrombus, lymph node positivity, and tumor rupture. On multivariate analysis, factors associated with increased risk of death were lymph node positivity and anaplasia. Factors correlated with probability of relapse in the univariate analysis were lymph node positivity, anaplasia, and female sex. All 3 of these factors were also independently significant on multivariate analysis. CONCLUSION Lymph node involvement and anaplasia are significantly correlated with probability of relapse and overall survival, reemphasizing the strong recommendation to sample regional lymph nodes during Wilms tumor resection.

Local control, survival, and operative morbidity and mortality after re-resection, and intraoperative radiation therapy for recurrent or persistent primary high-risk neuroblastoma

BACKGROUND/PURPOSE Patients with locally recurrent or persistent high-risk neuroblastoma are difficult to treat. We describe our experience using intraoperative radiation therapy (IORT) after re-resection in this high-risk population. METHODS We retrospectively reviewed 44 consecutive patients who received IORT at our institution between April 2000 and September 2009 after gross total resection of recurrent/persistent tumor. Specifically, we evaluated local recurrence rates, complications, and overall survival. RESULTS The median age at diagnosis was 41.5 months. Median follow-up after IORT was 10.5 months. Each patient received prior chemotherapy and surgery, while 94.5% had previous external beam radiation therapy. MYCN was amplified in 34% of patients. There were no operative or postoperative deaths, and 18 patients (40.9%) had postoperative complications. There was a 50.4% probability of local control. MYCN amplification did not affect local control (local recurrence rate of 53.9% vs 52.4%, P = .89). Median overall survival was 18.7 months (95% confidence interval, 11.7-25.6 months). Mean survival for MYCN-amplified patients was 13.0 vs 39.2 months for those without MYCN amplification (P = .035). CONCLUSIONS Intraoperative radiation therapy after re-resection of locally recurrent/persistent neuroblastoma results in a reasonable rate of local control with acceptable morbidity and survival. This approach should be considered in this high-risk population.

Early-stage non-Spitzoid cutaneous melanoma in patients younger than 22 years of age at diagnosis: long-term follow-up and survival analysis

PURPOSE We evaluated prognostic factors among young patients with early stage melanoma, with particular attention to survival, recurrence, and development of a second primary melanoma. METHODS We retrospectively reviewed patients (age <22 years) with pathologically confirmed in-situ and stage 1 non-Spitzoid melanoma treated at our institution from 1980-2010, assessing demographics, clinical presentation, treatment, disease-specific survival, recurrence-free survival, and probability of developing a second primary melanoma. RESULTS One hundred patients with in-situ melanoma (n=16) or stage 1A (n=48) or 1B (n=36) melanoma were identified. Median age was 19.4 years (range, 11.2-21.9), and median follow-up was 7.6 years (range, 0.1-31.7). Median tumor thickness was 0.76 mm (range, 0.23-2.0). No lesions were ulcerated. All patients underwent wide local excision with negative margins, and 21 had a concomitant negative sentinel lymph node biopsy (SLNB). Sixteen patients developed recurrences, and 8 subsequently died of progressive melanoma. There were 2 non-melanoma-related deaths. Endpoints were 20-year overall survival (77.4%), melanoma-specific mortality (20.1%), recurrence rate (34.0%), and probability of developing a second primary melanoma (24.7%). Greater tumor depth and Clark level were associated with worse prognosis, but age, sex, and tumor mitotic rate were not correlated with recurrence or survival. CONCLUSION Among younger early-stage melanoma patients, greater lesion depth conferred higher recurrence risk and mortality. Our data did not define the role of sentinel lymph node biopsy in this group.

A case of renal cell carcinoma after successful treatment of Wilms tumor

This case report documents the eighth reported case of renal cell carcinoma (RCC) occurring after treatment of Wilms tumor. Although secondary malignancies after treatment of Wilms tumors are not infrequent, RCC as the second malignancy is rare. We discuss a 17-year-old girl whose RCC was diagnosed 12.5 years after diagnosis of a Wilms tumor. In addition, we review the literature on the subject. Renal cell carcinoma has been proposed as a consequent of chemoradiation; however, a genetic susceptibility must be considered. Because it is routine to assess the functional status of the remaining solitary kidney by annual ultrasonography, we recommend assessing for the presence of secondary renal malignancies and perhaps continuing routine ultrasounds long-term.

Hodgkin lymphoma presenting with chest wall involvement: a case series

Chest wall tumors in the pediatric population can have a variety of etiologies, malignancy being the most worrisome. Hodgkin lymphoma (HL) rarely presents as a chest wall mass in the pediatric population. In this report, we describe 3 male pediatric patients, all of whom had chest wall masses present at the initial diagnosis of HL. We also discuss the literature on this topic. We conclude that malignancy and, more specifically, HL should always be considered when evaluating a pediatric patient who presents with a chest wall mass.

Endogenous Antibodies for Tumor Detection

The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies.