Diagnosis of neuroblastoma and ganglioneuroma using Raman spectroscopy

Background

Raman spectroscopy has proven to be useful in studying premalignant and malignant lesions in adults. This is the first report to evaluate Raman spectroscopy in the diagnosis and classification of neuroblastoma in children.

Methods

A biopsy or resection of fresh tissue samples from normal adrenal glands, neuroblastomas, ganglioneuromas, nerve sheath tumors, and pheochromocytoma at our hospital were equally divided between routine histology and spectroscopic studies. At least 12 spectra were collected from different regions of each sample using a Renishaw Raman microscope. Raw spectra were processed to remove noise, florescence, and shot noise, and then analyzed using principle component analysis and discriminant function analysis.

Results

We collected 698 spectra from 16 neuroblastomas, 5 ganglioneuromas, 3 normal adrenal glands, 6 nerve sheath tumors, and 1 pheochromocytoma. Raman spectroscopy differentiated between normal adrenal gland, and neuroblastoma and ganglioneuroma with 100% sensitivity and 100% specificity. It correlated well with the Shimada histologic classification system with 100% sensitivity and 100% specificity. It was also able to differentiate neuroblastoma from nerve sheath tumors and pheochromocytoma with high sensitivity and specificity.

Conclusion

This technique can differentiate neuroblastoma from ganglioneuroma and other tumors. It has a potential as a noninvasive real-time diagnostic tool in classifying pediatric tumors.     

Omentopexy improves vascularization and decreases stricture formation of esophageal anastomoses in a dog model

Background

Anastomotic strictures are common after primary esophageal anastomosis in pediatric patients. Recent studies provided evidence that omentopexy may improve vascularization of gastroesophageal anastomoses and decrease the rate of stricture-related complications. The effect of omentopexy on primary esophago-esophageal anastomosis, however, is unknown. The aim of the current study was to examine the role of omentopexy on the healing process of primary midesopageal anastomoses.

Methods

Six dogs were operated on. A 5-cm portion of the midesophagus was resected, and continuity was restored by end-to-end anastomosis. In 3 dogs, an omental pedicle was placed around the anastomotic region. Eating patterns were recorded and functional swallowing was evaluated by fluoroscopic studies. Eight weeks after the operations, the experimental animals were killed and anastomotic lumen diameters and vascularization of the anastomotic sites were evaluated by radiographic studies and histologic examination, respectively.

Results

Two dogs in the omentopexy group were able to resume regular feeding, whereas none of the dogs in the control group were able to tolerate solid food intake. Fluoroscopic studies found preserved motility patterns of the esophagus in the omentoesophagopexy group, while prestenotic dilatation and delayed food clearance through the anastomosis were observed in the control group. Histologically, neovascularization was observed at the anastomotic site in the omentoesophagopexy group in contrast to the marked degree of fibrosis displayed in the control group.

Conclusions

Omentopexy may improve vascularization and decrease stricture formation after primary esophagoesophageal anastomosis.     

Ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation for fetal thoracic masses

Purpose

We describe our experience with fetuses diagnosed with life-threatening chest masses who were delivered by ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation (EXIT-to-ECMO).

Methods

The first fetus presented with a cystic mediastinal mass and enlarging echogenic lungs. Bronchoscopic evaluation during ex utero intrapartum treatment (EXIT) revealed complete airway obstruction secondary to a carinal bronchogenic cyst. The second fetus presented with a massive left congenital cystic adenomatoid malformation. The EXIT procedure was performed because of significant mediastinal shift, severe compression of the normal lung parenchyma, and signs of fetal distress.

Results

In both cases, extracorporeal membrane oxygenation (ECMO) was initiated while on placental support. The fetuses were then delivered, and a definitive resection of their thoracic lesions was successfully performed. There were no major perioperative complications. Both children made expedient recoveries without significant cardiopulmonary sequelae.

Conclusion

To our knowledge, this is the first report describing the successful use of EXIT-to-ECMO as a bridge to definitive resection of large chest masses diagnosed in utero. EXIT-to-ECMO is a novel and effective management strategy for stabilizing patients with profound respiratory compromise secondary to congenital thoracic lesions.     

Gastric malignancies in breast cancer survivors: Pathology and outcomes

Background

As the number of breast cancer survivors increases, the appearance of second malignancies and unusual metastatic patterns likely also is increasing. In particular, we and others have observed gastric malignancies in breast cancer survivors.

Methods

We reviewed 3 regional hospital system tumor databases, comprising 19,049 analytic breast cancer cases, to determine the number, types, and outcomes of subsequent gastric malignancies.

Results

Twenty-eight patients developed subsequent gastric malignancies, representing .15% of breast cancer survivors; 82% of patients had gastric symptoms. Overall survival for the cohort was 39%. Twenty-four patients (86%) had gastric primaries and 13 died of their second cancers. Four patients had gastric metastases; all had lobular histology in both their primary tumors and metastatic lesions. Five patients had gastrointestinal stromal tumors; all patients underwent resection and currently are alive.

Conclusion

Gastric symptoms in breast cancer survivors may represent malignant lesions, often second primaries. All gastric metastases in our series were of lobular histology.     

Histologic oddities at the porta hepatis in biliary atresia

Purpose

Highly unusual histologic findings at the porta hepatis in 3 infants who underwent Kasai portoenterostomy for biliary atresia are reported.

Methods

Portoenterostomy was performed using a standard operative technique. Serial transverse sections of the excised portal plate were examined by light microscopy along with sections from the distal extrahepatic biliary remnants, gallbladder, and liver biopsy.

Results

Of 61 consecutive infants who underwent Kasai portoenterostomy for biliary atresia, 3 were found to have highly unusual histologic features at the porta hepatis. All had type 3 biliary atresia. Two had hilar biliary ductules lined in part by squamous epithelium, and the third had a focus of mature hyaline cartilage surrounded by perichondrium adjacent to biliary ductules. In each case, these unusual histologic features were localized to the porta hepatis in the region of the transected portal plate.

Conclusions

The presence of hyaline cartilage at the portal plate is likely to be an expression of defective morphogenesis, thus supporting the concept of disordered embryogenesis in the etiology of biliary atresia. Squamous epithelium within biliary ductules might also reflect a similar mechanism but could alternatively be an unusual metaplastic response to inflammation at this site.     

The predictive value of preoperative fluorine-18-L-3,4-dihydroxyphenylalanine positron emission tomography-computed tomography scans in children with congenital hyperinsulinism of infancy

Background/Purpose

In congenital hyperinsulinism (CHI) of infancy, the use of preoperative fluorine-18-l-3,4-dihydroxyphenylalanine-positron emission tomography-computed tomography (¹⁸F-DOPA-PET-CT) scan has recently been reported. The aim of this study was to evaluate the accuracy of this technique in discriminating between diffuse and focal CHI and the anatomical localization of focal lesions.

Methods

Between 2006 and 2010, ¹⁸F-DOPA-PET scan was performed in 19 children with CHI (median age, 2 months; range, 1-12 months) who were not responding to medical therapy and underwent laparoscopic or open surgery. The findings of ¹⁸F-DOPA-PET scan were correlated with histology.

Results

In 5 children, ¹⁸F-DOPA-PET scan showed diffuse pancreatic uptake, confirmed at histology and supporting the genetic suspicion of diffuse disease. In 14 children, ¹⁸F-DOPA-PET scan indicated focal pancreatic uptake, which corresponded to histology. However, in 5 patients (36%), ¹⁸F-DOPA-PET scan was inaccurate in defining the location of the lesion (n = 3), size of the lesion (n = 1), or both location and size (n = 1), leading to an inaccurate pancreatic resection.

Conclusions

Fluorine-18-l-3,4-dihydroxyphenylalanine-positron emission tomography-computed tomography scan discriminates between diffuse and focal forms of CHI. In focal forms, ¹⁸F-DOPA-PET scan is useful in 2/3 of patients in defining the site and dimension of the focal lesion. Intraoperative histologic confirmation of complete focal lesion resection is needed.     

Antenatally suspected congenital cystic adenomatoid malformation of the lung: postnatal investigation and timing of surgery

Background

We have previously reported the outcome of a cohort of cases over a 10-year period with antenatally suspected congenital cystic adenomatoid malformation (CCAM) and have recommended elective surgery within the first year of life for persistent, asymptomatic cases because of the risk of long-term complications. The aims of this study were to document optimal postnatal investigation and timing of surgery.

Methods

Cases were identified using the Oxford Congenital Anomaly Register, theatre records, and histopathology reports. Nineteen cases from 2003 onwards were reviewed with respect to postnatal imaging with chest x-ray and computed tomography scan and timing of surgery.

Results

Chest x-ray was poor at detecting CCAM with only 61% sensitivity. Computed tomography scan was 100% sensitive with no false-positive diagnoses.Of the 19 cases since 2003, 13 cases were asymptomatic and had elective surgery. Eight had surgery at 6 months of age or older, and of these, 4 (50%) had evidence of chronic inflammation/infection on histology including 1 case with multiple abscesses found at surgery and 1 case with multiple adhesions. Five cases had surgery at less than 6 months of age and only 1 of these, aged 5.5 months, had evidence of infection present at histology.

Conclusions

All cases of antenatally suspected CCAM should be followed up postnatally and investigated with computed tomography scan. Elective surgery in asymptomatic cases, at around 3 to 6 months of age, is recommended for persistent lesions because of the risk of long-term complications.     

Pediatric rib lesions: a 13-year experience

Background

Rib lesions in the pediatric population are rare but significant processes and are often neoplastic.

Methods

All patients with primary rib lesions evaluated by the Department of Surgery at Children's Hospital Boston from 1992 to 2005 were studied. The patient's diagnosis, sex, symptoms and their duration, radiologic evaluation, biopsy status, surgical procedure, and follow-up were assessed.

Results

Thirty-three patients, ages 3 to 23 years (median, 12.7 years), were evaluated. Sixteen patients (48%) had benign and 17 (52%) had malignant lesions. Within the benign cohort of 16 patients, there were 6 osteochondromas, 4 aneurysmal bone cysts, and 2 fibrous dysplasias as well as 1 of each of the following: enchondroma, periosteal chondroma, eosinophilic granuloma, and chondrophyte. Within the malignant cohort of 17 patients, 13 were diagnosed with Ewing's sarcoma, 3 with osteogenic sarcoma, and 1 with chondrosarcoma. The sex distribution for the malignant group was 11 (65%) females and 6 (35%) males.

Conclusions

Rib tumors are rare entities in the pediatric population. However, a significant number of rib lesions are malignant. Therefore, proper diagnosis and expeditious treatment are critical.     

Atrial Flutter after Heart Transplantation: Mechanism and Catheter Ablation

Background

Atrial flutter is a frequent arrhythmia after heart transplantation, but little is known about its mechanism and treatment. We report the results of an electrophysiologic study in patients with atrial flutter after orthotopic heart transplantation, describing its mechanism and demonstrating the acute and long-term efficacy of catheter ablation for treating this arrhythmia.

Methods

We included 14 patients with symptomatic atrial flutter after orthotopic heart transplantation. All of them underwent an electrophysiologic study to determine the mechanism of the arrhythmia and catheter ablation when possible.

Results

Counterclockwise right atrial circuit around the tricuspid annulus involving the cavotricuspid isthmus was demonstrated in 13 patients (86%). Catheter ablation of the isthmus was performed with good acute results in all but 1. During a mean follow-up of 24 ± 17 months, recurrent atrial flutter was documented in 3 patients and atrial fibrillation in 2. In another patient, we demonstrated a left atrial origin.

Conclusions

The most common mechanism of atrial flutter in heart transplant recipients is a counterclockwise circuit around the tricuspid annulus involving the cavotricuspid isthmus. Catheter ablation of the isthmus between tricuspid annulus and posterior atrial suture line represents an effective treatment in these patients. This condition may be avoided by changing the surgical technique to a bicaval anastomosis.     

Surgical management of lipoblastoma

Background/Purpose

Lipoblastoma/lipoblastomatosis, a rare benign pediatric tumor composed of embryonic fat, most often presents as a rapidly growing mass in children younger than 3 years. This benign tumor locally recurs up to 25% of the time. This retrospective review was done to emphasize problems with diagnosis, management, and the approach to follow-up care.

Methods

Sixteen cases of pathologically proven lipoblastoma presenting to a single institution over a 16-year period (1988-2004) were reviewed retrospectively for clinical features and outcome.

Results

There were 11 males and 5 females ranging in age from 18 days to 12.75 years. Preoperative diagnoses were accurate in only 3 cases. Two lesions recurred locally over a period of 10 months and 5 years. One lesion presented with local infiltration. Six lesions were right-sided, 5 were left-sided, and 5 were midline.

Conclusions

It is important to consider lipoblastoma in the diagnosis of a rapidly enlarging fatty mass in children. Complete resection is the only definitive treatment and should not be delayed when impingement on surrounding structures is imminent. There is a tendency for these lesions to recur despite presumed complete excision. Therefore, follow-up for a minimum of 5 years is recommended.     

The use of positron emission tomography in detecting hepatoblastoma recurrence--a cautionary tale

Purpose

The use of positron emission tomography (PET) with [18F] fluorodeoxyglucose (FDG) in the detection of recurrences has been well established in many tumor types. Here the authors present their experience using this modality in the evaluation of posttreatment hepatoblastoma patients.

Methods

The authors conducted a retrospective review on patients with hepatoblastoma diagnosed from 1996 to 2003. FDG-PET imaging was performed together with measurement of alpha-fetal protein (AFP) during posttreatment follow-up.

Results

Sixteen patients (8 boys and 8 girls) were identified in this series. The mean age was 23.5 months (range, 5 months to 4 years). Three posttreatment patients had PET results suggestive of tumor recurrence. One of these patients had normal AFP level and suspected recurrence in the caudate lobe. Radiologic-guided biopsy was performed 3 times, and there was no evidence of tumor. The other 2 patients underwent further liver resections because of mildly raised AFP levels. The histology of these showed regenerative liver tissue only with no hepatoblastoma recurrence.

Conclusions

Although PET has been gaining popularity as a tool in the detection of tumor recurrences worldwide, it has been shown in this series that PET may not be useful in hepatoblastoma patients, and caution must be taken in the interpretation of positive results.     

Postnatal spontaneous resolution of congenital cystic adenomatoid malformations

Purpose

Although antenatal resolution of congenital cystic adenomatoid malformations (CCAMs) is well documented, complete spontaneous postnatal resolution is rare, its existence even questioned by some.

Methods

All cases of antenatally diagnosed CCAMs over 7 years were retrospectively reviewed. Inclusion criteria were the following: (1) antenatal diagnosis of CCAM, (2) persistence on postnatal imaging, and (3) subsequent spontaneous resolution on postnatal imaging.

Results

Of 56 antenatally diagnosed CCAMs, 2 patients were identified. Both had macrocystic lesions. In case 1, the CCAM that filled the hemithorax on antenatal ultrasound was smaller on postnatal chest radiograph and disappeared by age 37 months on computed tomography. Case 2 had significant reduction of the CCAM at birth (persistence of the lesion on initial radiographs and ultrasound was documented). By 5 months, the lesion was not evident on computed tomography. Neither case was associated with symptoms, polyhydramnios, hydrops, or other abnormalities.

Conclusions

In patients with an antenatal diagnosis of CCAM, spontaneous resolution may occur postnatally in 4% of cases. Significant reduction in CCAM size may portend possible disappearance and therefore warrants an observational period before resection.     

Prenatal covering of the spinal cord decreases neurologic sequelae in a myelomeningocele model

Background/Purpose

Recent experience in fetal surgery to correct myelomeningocele in humans reports an early reversion of hydrocephalus and decreased need of ventricular shunting in the first months of life; however, it has not been possible to demonstrate benefit in lower extremity function. In the present work, we have tried to ascertain the impact of cord exposure on hind limb function.

Methods

Fetal rabbits with myelomeningocele (group M), treated myelomeningocele (group T), and control animals (group C) were compared at birth regarding physical examination, somatosensory-evoked potentials of the hind limbs, ventricular morphometry, and spine histology.

Results

No major difference was found between groups M and T in the physical examination. Somatosensory-evoked potentials of the hind limbs were absent in group M and present in group T, although showing a longer latency period and decreased amplitude than controls. The area of the third ventricle was significantly larger in group M than in group C; in group T, it was also somewhat larger but not significantly so. Cord histology had evident changes in group M and minor changes in group T, which resembled normal group C cord.

Conclusions

Prenatal covering of the spinal cord prevents central and peripheral neurologic deterioration in this animal model of myelomeningocele.     

ET-Kyoto Ductal Injection and Density-Adjusted Purification Combined With Potent Anti-Inflammatory Strategy Facilitated Single-Donor Islet Transplantation: Case Reports

Background

The necessity to use multiple donors for achieving insulin independence in clinical islet transplantation is still a major issue. We have developed a modified islet isolation method for non-heart-beating donors (Kyoto method) to significantly increase islet yield. In this study, we further modified the method for brain-dead donors and in addition, introduced a potent anti-inflammatory strategy aiming for single-donor islet transplantation.

Materials and methods

Two islet isolations used pancreatic ductal preservation with the modified Kyoto solution and a density-adjusted purification method. Anti-interleukin-1-beta antibody (Anakinra) and anti-tumor necrosis factor-alpha (Eternacept) were administered during and after transplantation. The efficacy of the islet transplantation was assessed by the insulin requirement and SUITO (Secretory Unit of Islet Transplant Objects) index, wherein a value of more than 26.0 seems to be associated with insulin independence.

Results

Both isolated islet preparations met the criteria for transplantation. They were transplanted into two type 1 diabetic patients, both of whom became insulin independent with stable glycemic control. The average SUITO index within 1 month was 29.2 and 45.3.

Conclusion

The islet isolation method combined with a potent anti-inflammation strategy made it possible to achieve single-donor islet transplantation achieving a high SUITO index.