Patterns of lymph node sampling and the impact of lymph node density in favorable histology Wilms tumor: An analysis of the national cancer database.

INTRODUCTION: There is controversy about the role of lymph node (LN) sampling or dissection in the management of favorable histology (FH) Wilms tumor (WT), specifically how it performed and how it may impact survival. OBJECTIVE: The objective of this study was to analyze factors affecting LN sampling patterns and the impact of LN yield and density (number of positive LNs/LNs examined) on overall survival (OS) in patients with advanced-stage favorable histology Wilms tumor (FHWT). METHODS: The National Cancer Database (NCDB) was queried for patients with FHWT during 2004-2013. Demographic, clinical and OS data were abstracted for those who underwent surgical resection. Poisson regression was performed to analyze how factors influenced LN yield. Patients with positive LNs had LN density calculated and were further analyzed. RESULTS: A total of 2340 patients met criteria, with a median age at diagnosis of 3 years (range 0-78 years). The median number of LNs examined was three (range 0-87). Lymph node yield was affected by age, race, insurance, tumor size, laterality, advanced stage, LN positivity, and institutional volume. A total of 390 (16.6%) patients had LN-positive disease. Median LN density for these LN-positive patients was 0.38 (range 0.02-1) (Summary Figure). Estimated 5-year OS was significantly improved for those with LN density ≤0.38 vs. >0.38 (94% vs. 84.6%, P = 0.012). In this population, on multivariate analysis, age and LN density were significant predictors of OS. DISCUSSION: It is difficult to compile large numbers of cases in rare diseases like WT, and fortunately a large administrative database such as the NCDB can serve as a great resource. However, administrative data come with inherent limitations such as missing data and inability to account for a variety of factors that may influence LN yield and/or OS (specimen designation, pathologist experience, surgeon experience/volume, institutional Children's Oncology Group (COG) association, etc.). In this specific disease, the American Joint Committee on Cancer staging (captured by the NCDB) is different than the COG WT staging system that is used clinically, and the NCDB does not capture oncologic outcomes beyond OS. CONCLUSIONS: In a review of the NCDB, various factors associated with LN yield and observed LN density were identified to be significantly associated with OS in patients with LN-positive FHWT. This reinforces the need for adequate LN sampling at the time of WT surgery, to maximize surgical disease control. It was proposed that LN density as a metric may allow for improved risk-stratification, and possibly allow for therapeutic reduction in a sub-set of patients with low LN density.

Image based feasibility of renal sparing surgery for very low risk unilateral Wilms tumors: a report from the Children's Oncology Group.

PURPOSE: Nephrectomy with lymph node sampling is the recommended treatment for children with unilateral Wilms tumor under the Children's Oncology Group protocols. Using radiological assessment, we determined the feasibility of performing partial nephrectomy in a select group of patients with very low risk unilateral Wilms tumor. MATERIALS AND METHODS: We reviewed imaging studies of 60 patients with a mean age of less than 2 years with very low risk unilateral Wilms tumor (mean weight less than 550 gm) to assess the feasibility of partial nephrectomy. We evaluated percentage of salvageable parenchyma, tumor location and anatomical features preventing a nephron sparing approach. RESULTS: A linear relationship exists between tumor weight and computerized tomography estimated tumor volume. Mean tumor weight in the study population was 315 gm. Partial nephrectomy was deemed feasible in only 5 of 60 patients (8%). CONCLUSIONS: When considering a select population with very low risk unilateral Wilms tumor (lower volume tumor), only a small percentage of nonpretreated patients are candidates for nephron sparing surgery.

Presentation of low anorectal malformations beyond the neonatal period.

OBJECTIVE: Anorectal malformations are usually diagnosed at birth, but some patients have presented to this institution beyond the early newborn period without recognition of their anorectal malformations. To quantify the extent of this problem, we undertook a review of all patients presenting to this hospital with anorectal malformations. METHODS: We reviewed all new cases of anorectal malformations treated at British Columbia's Children's Hospital during the past 11 years. We looked specifically at the time of diagnosis, patient age, sex and mode of presentation, the type of anorectal malformations, and any associated anomalies. RESULTS: One hundred twenty new cases of anorectal malformations were seen here, of whom, 15 patients (9 girls and 6 boys) presented beyond the early newborn period. Of these, 1 male infant was diagnosed at 2 weeks of age and another girl at 14 years of age. The remaining 13 presented between 3 and 11 months of age because of increasing constipation, usually associated with the introduction of solid foods. All had low anorectal malformations. Nine patients had at least 1 other feature of the VACTERL complex. CONCLUSIONS: Most anorectal malformations are identified at birth, but a significant number of the milder lesions may not be recognized until later. Therefore, this condition must be considered in older infants and children presenting with constipation, particularly if they also have cardiac or genitourinary anomalies. constipation, imperforate anus, VACTERL.

Local staging of Wilms' tumor--computerized tomography correlation with histological findings.

PURPOSE: The aim of this study was to assess the accuracy of computed tomography (CT) in the local staging of Wilms' tumor. METHODS: Twenty-six patients with unilateral, nonmetastatic Wilms' tumors were accrued over the period of 1990 through 1997. Preoperative CT staging was performed before surgical biopsy or excision. The abdominal CT images were reviewed and staged for local disease according to National Wilms' Tumour Study (NWTS) Group Staging V as either intrarenal disease (Stage I), local extrarenal extension amenable to complete local excision (Stage II), or advanced local disease (Stage III). Patients with metastatic (Stage IV) and bilateral disease (Stage V) were excluded from our study. Results were compared to histological findings. RESULTS: CT scan correctly staged 10 of 26 cases (38%) of Wilms' tumor. CT scan overstaged 12 of 16 (75%) localized renal disease (Stage I) and local extension (Stage II) tumors, and understaged 4 of 10 (40%) localized spread (Stage III) tumors. CONCLUSIONS: CT scan appears to have poor correlation to histological staging. Therefore, basing therapy solely on radiological imaging may lead to some patients receiving more intense therapy than necessary, whereas others do not receive sufficient therapeutic regimens. Histological assessment of the excised mass should remain the standard for staging Wilms' tumors.

Breast cancer in a 6-year-old child.

A 6-year-old girl presented for a second opinion with a 1-year history of an enlarging soft tissue mass just lateral to the right areola. She had been seen by a pediatric surgeon elsewhere who reassured the parents that the lesion was benign. Ultrasound scan showed a 1.5- x 1.5-cm cystic structure adjacent to the right breast bud. Excisional biopsy results showed secretory ductal adenocarcinoma. Modified radical mastectomy with axillary node dissection was performed. All 11 nodes were negative for metastatic disease. She is now disease free 3 years after diagnosis. Estrogen-progesterone receptors were negative, as was screening for BCR 1 and 2. This is the first report of cytogenetics showing an abnormal cell line with a reciprocal translocation between 12p and 15q. Although breast cancer is extremely rare in children, a history of a painless, enlarging, firm breast mass should raise concern about possible neoplastic disease. Cystic appearance on ultrasound scan caused by the pseudocapsule around the tumor may be a marker for secretory carcinoma. Histological evaluation of all suspicious masses should be obtained. Because of the risk of local recurrence and axillary metastases, the authors recommend modified radical mastectomy with axillary node dissection for children with secretory carcinoma of the breast.

Traumatic intercostal hernia: presentation and diagnostic workup.

Intercostal herniation of lung caused by nonpenetrating thoracic trauma is rare in the pediatric population. An 11-year-old boy presented with such a hernia 4 years after the original injury. The hernia was increasing in size and was becoming more difficult to reduce. In view of possible future strangulation, a surgical repair was undertaken with prosthetic mesh closure of the intercostal muscle defect. Intercostal hernias are rare, but familiarity with the proper investigation and treatment to be provided is important.

Effect of crystalloid administration on oxygen extraction in endotoxemic pigs.

We asked whether crystalloid administration improves tissue oxygen extraction in endotoxicosis. Four groups of anesthetized pigs (n = 8/group) received either normal saline infusion or no saline and either endotoxin or no endotoxin. We measured whole body (WB) and gut oxygen delivery and consumption during hemorrhage to determine the critical oxygen extraction ratio (ERO2 crit). Just after onset of ischemia (critical oxygen delivery rate), gut was removed for determination of area fraction of interstitial edema and capillary hematocrit. Radiolabeled microspheres were used to determine erythrocyte transit time for the gut. Endotoxin decreased WB ERO2 crit (0.82 +/- 0.06 to 0.55 +/- 0.08, P < 0.05) and gut ERO2 crit (0.77 +/- 0.07 to 0.52 +/- 0.06, P < 0.05). Unexpectedly, saline administration also decreased WB ERO2 crit (0.82 +/- 0.06 to 0.62 +/- 0.08, P < 0.05) and gut ERO2 crit (0.77 +/- 0.07 to 0.67 +/- 0.06, P < 0.05) in nonendotoxin pigs. Saline administration increased the area fraction of interstitial space (P < 0.05) and resulted in arterial hemodilution (P < 0.05) but not capillary hemodilution (P > 0.05). Saline increased the relative dispersion of erythrocyte transit times from 0.33 +/- 0.08 to 0.72 +/- 0.53 (P < 0.05). Thus saline administration impairs tissue oxygen extraction possibly by increasing interstitial edema or increasing heterogeneity of microvascular erythrocyte transit times.

Oxygen uptake during peritoneal ventilation in a porcine model of hypoxemia.

OBJECTIVES: Peritoneal ventilation (PV) can greatly increase PaO2 in hypoxemic rabbits. We tested the hypothesis that the peritoneum can provide a gas exchange surface for oxygen uptake in larger animals that, like humans, have a smaller relative peritoneal surface area and corresponding blood flow. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. INTERVENTIONS: In six anesthetized pigs, a modified endotracheal tube (9.0-inner diameter) was inserted into the peritoneal cavity, and the peritoneal cavity was ventilated with oxygen in helium in gas phase. Measurements of peritoneal oxygen uptake and mixed venous oxygen saturation were made over 30 mins of: a) baseline FiO2 0.20, no PV; b) FiO2 0.20, PV; c) FiO2 0.20, PV, dopamine 5 microg/kg/min; d) baseline FiO2 0.15, no PV; e) FiO2 0.15, PV; and f) FiO2 0.15, PV, dopamine 5 microg/kg/min. MEASUREMENTS AND MAIN RESULTS: Mixed venous oxygen saturation was 61% at the baseline FiO2 of 0.20 and 33% at an FiO2 of 0.15 and did not increase significantly from baseline with PV or with dopamine at either FiO2. Peritoneal oxygen uptake, measured with a waterseal spirometer, was 9.1+/-3.1 (SD) and 11.9+/-3.0 mL/min when lung FiO2 was 0.20 and 0.15, respectively, and 9.7+/-2.8 and 12.2+/-2.7 mL/min when FiO2 was 0.20 and 0.15 and dopamine was infused, respectively. CONCLUSION: Peritoneal ventilation does not result in clinically significant oxygen uptake or alter mixed venous oxygen saturation in a porcine model of hypoxemia.

Traumatic perforation of duodenal diverticulum.

A fragile 72-year-old female with previous coronary artery disease sustained blunt abdominal trauma in a motor vehicle crash. A ruptured duodenum was identified by computed tomography scanning. Exploratory laparotomy revealed that the duodenal rupture was caused by perforation of a diverticulum in the second portion of the duodenum. The surgical management of the injury to the duodenum is described in detail.

Multiple entero-entero fistulae: an unusual complication of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is an immunologically mediated systemic vasculitis of small blood vessels that frequently involves the gastrointestinal tract. Surgeons often are asked to assess patients with HSP for abdominal pain. Common complications that lead to surgical intervention include intussusception, perforation, necrosis, and massive gastrointestinal bleeding. However, the development of multiple entero-entero fistulae has not been described previously. Herein the authors describe the case of a 10-year-old girl with HSP who had a typical rash, seizures secondary to central nervous vasculitis, and gastrointestinal involvement. The abdominal pain persisted for several days until marked fever and hypotension developed, which necessitated surgical intervention. During laparotomy, multiple entero-entero fistulae of the ileum were found, which required resection and primary anastomosis. Histological examination of the ileum was consistent with HSP vasculitis. The patient made an unremarkable recovery and has had no recurrence of symptoms.

Splanchnic artery pseudo-aneurysms secondary to blunt abdominal trauma in children.

Traumatic splanchnic artery pseudo-aneurysms are uncommon; only two cases have been reported among the pediatric population. The authors describe their experience with four patients in whom splanchnic artery pseudoaneurysms developed after blunt abdominal trauma. Splenic artery pseudo-aneurysms were found in a 6-year-old boy and an 8-year-old girl after blunt splenic injuries. In both cases, spontaneous thrombosis of the pseudo-aneurysms occurred after a period of observation. Hepatic artery pseudoaneurysms were found in a 7-year-old boy and a 10-year-old girl after major liver lacerations. The boy had successful angiographic embolization of the lesion, but the girl required direct ligation of the pseudo-aneurysm after nearly exsanguinating from acute hemorrhage. All four children have recovered completely, with no long-term sequelae. Traumatic splanchnic artery pseudo-aneurysms are potentially life-threatening complications that can occur after blunt abdominal trauma. The investigation and management of these lesions must be individualized according to the clinical scenario.

Validity of visual inspection of diagnostic peritoneal lavage fluid.

OBJECTIVE: To determine the positive and negative predictive values of visual inspection of peritoneal lavage fluid and the threshold concentration of erythrocytes for diagnosing significant hemoperitoneum by this method. DESIGN: Nineteen residents in surgery and 21 staff surgeons were asked to inspect mock peritoneal lavage fluid and state whether they would proceed with urgent laparotomy. MAIN RESULTS: The overall positive and negative predictive values for visual inspection were 52.0% and 98.9%, respectively. The threshold for diagnosing significant hemoperitoneum by visual inspection was between 10,000 and 20,000 erythrocytes/mL for most subjects. There were no significant differences between residents and staff surgeons. CONCLUSIONS: Visual inspection of peritoneal lavage fluid has good negative but poor positive predictive value, and the threshold for diagnosing significant hemoperitoneum by visual inspection is less than 100,000 erythrocytes/mL. Therefore, patients whose condition is stable and for whom visual inspection of lavage fluid indicates apparently significant hemoperitoneum should not undergo laparotomy without confirmation by laboratory testing.

Obstructive jaundice caused by neuroblastoma managed with temporary cholecystostomy tube.

Neuroblastoma presenting as obstructive jaundice is very rare. The authors present two cases of neuroblastoma, one primary and one recurrent, manifesting as a malignant obstruction of the extrahepatic biliary system. Various methods of biliary decompression were considered in these children including transhepatic or retrograde biliary stenting and internal cholecystoenteric bypass. An attempt at percutaneous transhepatic stent placement failed in one case. In each patient, a simple insertion of a cholecystostomy tube proved effective. Immediately postoperatively, both patients had rapid resolution in symptoms and a decrease in bilirubin levels. Transient mild cholangitis in both children was successfully treated with antibiotics. Chemotherapy reduced the tumor size in each case, and the cholecystostomy tubes were removed within 3 weeks, after cholangiography showed patency of the distal common bile ducts. Temporary cholecystostomy tube drainage and systemic chemotherapy proved to be a safe, simple, and effective method for managing obstructive jaundice caused by neuroblastoma in these two cases.

A stimulatory effect of interleukin-1 on adrenocortical cortisol secretion mediated by prostaglandins.

Studies using cultured bovine adrenocortical cells now demonstrate that the cytokines interleukin-1 (IL-1) alpha and beta, contrary to previous reports, can stimulate cortisol secretion in vitro in a dose- and time-dependent fashion. However detectable levels of IL-1 receptor could not be demonstrated in adrenal cortical, medullary, or capsular cells by membrane displacement of iodinated IL-1 alpha by unlabeled IL-1 beta, a technique that readily demonstrates specific IL-1 alpha-binding sites on 3T3 fibroblasts. The stimulatory effect of IL-1 on cortisol secretion could be totally blocked by indomethacin, an indication that this effect might be mediated indirectly via local release of prostaglandins (PGs). Subsequent investigations have confirmed that IL-1 does enhance the conversion of [3H]arachidonate to PGs by cultured adrenal cells, and that some of these PGs (PGD2, PGF2 alpha, and PGE2), in turn, can stimulate cortisol production. Taken together these observations suggest that IL-1-induced stimulation of cortisol secretion is mediated through local release of PGs by a small subpopulation of cells within the adrenal gland.