How often are common bile duct stones found in children suspected of having them?

This read stemmed from a literature search looking for articles addressing missed CBD stones in children not suspected of having them (no hx of jaundice, pancreatitis, normal CBD on U/S etc..). Instead I ran into this interesting article, out of Sick Kids in Toronto, looking at kids with findings consistent with CBD stones who were either managed by pre-operative ERCP, or had undergone an intra-operative cholangiogram, followed by ERCP when the IOC was positive.

202 patients with gallbladder stones, 48 of whom (23.7%) had suspected CBD stones. Preoperative ERCP, which was performed on a third of patients with suspected CBD stones, was positive in 21.4% of cases. Most of the rest of patients with suspected CBD stones underwent an IOC, which was positive in 6.5% of cases. Based on their results, the authors recommended an IOC as the initial investigative study since it involves less risk to the patient than does an ERCP, which was negative in around 80% of cases.

An IOC seems to be an excellent way to avoid unnecessary ERCP's, as long as a skilled gastroenterologist with a high ERCP success rate is available (to avoid a situation where a CBD stones are identified intraop, and an attempt at ERCP fails post op!). What is interesting about this study is the discrepancy between the finding of stones in the preoperative ERCP group and the IOC group. This could be because the ERCP may be more sensitive than the IOC, but potentially there might have been a selection bias, where patients who were more likely to have CBD stones (elevated bilirubin (8 vs 2), markedly dilated CBD (14 vs. 7) etc...) might have been selected to undergo and ERCP vs IOC.

Reference
Mah et al. Management of suspected CBD stones in children: role of selective IOC and ERCP. Journal of pediatric surgery (2004)39 :808-812

How can laparoscopy help evaluate patients with suspected rotational anomalies?

Again, the subject of rotational anomalies and equivocal UGI findings came up. The next day, this paper by Hsiao et al out of Sick Kids in Tornoto was in JPS. Here the authors discuss the utility of diagnostic laparoscopy as a tool to help corroborate UGI findings, or as a tie breaker for equivocal UGI studies.

The article was based on two premises. The first is what defines malrotation vs. non-rotation. Malrotation, here, was defines as the DJJ and the cecum near the midline, and the base of the mesentery less than 50% of the diameter of the abdomen. Non-rotation was defined as DJJ to the right of midline, ceceum in the lower left or central abdomen, small bowel on the left side, colon on the right, and base of mesentery is longer than 50% of the diameter of the abdomen. The other premise is that the small bowel is not at risk of midgut volvulus when the base of the mesentery is longer than 50% of the diameter of the abdomen (as in normal and non-rotation), and a Ladd's procedure is not necessary.

Very few people would argue that an infant with bilious emesis who is found to have an abnormal UGI needs exploration. The issue becomes more controversial when abnormal UGI studies are found in children with no symptoms or chronic and/or non-specific symptoms. This is the group of patients this paper addressed.

The UGI results studies included findings consistent with malrotation, malrotation with volvulus, non-rotation, or equivocal findings. Of the patients with UGI findings consistent with malrotation, ~60% had malrotation confirmed by laparoscopy (with or without volvulus), and the rest had either non-rotation (30%) or were normal (10%) (both conditions the authors believe do not need surgical correction). When UGI's showed non-rotation, laparoscopic evaluation was consistent with the diagnosis in all patients. Finally, of the patients with an equivocal UGI, a third had malrotation with/without volvulus, and the rest were found to be either non-rotated (48%) or normal (21%) on laparoscopic evaluation.

So if we accept that a mesenteric base longer than 50% of the diameter of the abdomen constitutes a stable mesenteric base not prone to volvulus (a finding confirmed by laparoscopy), laparoscopy can be an important tool that can help us manage this perplexing population of patients with no/vague symptoms and inconclusive UGI studies.


Reference:
Hsiaoo M, Langer JC. Value of laparoscopy in children with a suspected rotation abnormality on imaging. Journal of Pediatric Surgery (2011) 46, 1347-1352

Swimming with Sharks

Tumor spillage and Wilm's tumor: types and implications

Tumor spillage during resection of a Wilm's tumor has substantial implications on prognosis and therapy. Spillage immediately upstages a patient to Stage III, and depending on the type of spillage, commits the patient to either flank (local spillage) or total abdominal radiation (diffuse spillage).

Intraoperative recognition and documentation of spillage, whether pre-exiting or secondary to manipulation, thus has substantial implications on adjuvant therapy. With that in mind, it is important understand the different types of spillage or peritoneal soilage by tumor.

Based on the COG's AREN03B2 Renal Biology Protocol handbook (2010), the peritoneum is concidered soiled (tumor spill) when:

1. There is intraoperative tumor spillage
2. The tumor is biopsied
3. The tumor has ruptured

Spillage occurs whenever the tumor capsule is violated. If adherent organs (eg. diaphragm) are resected without violation of the capsule, this is not considered spillage. Whenever one cuts across tumor, including tumor present within vessels, or the tumor is removed in more than one piece, spillage is assumed to have occurred.

Tumor biopsy, whether done through a percutaneous anterior or retroperitoneal approach, or using an open approach, is considered local spillage unless indicated otherwise by the surgeon.

Tumor rupture can be spontaneous or post-traumatic with subsequent tumor cell dissemination in the peritoneal cavity. Tumor rupture is usually considered diffuse soilage, though in some cases it may be clearly isolated to the retroperitoneal space and considered local spillage. The presence of a hematoma implies tumor cell spread and diffuse soilage.

Because of the various types of soilage, and their different implications (either flank or total abdominal radiation), the surgeon should completely and clearly document how the soilage occurred and whether it was thought to be diffuse or local. If tumor thrombus is encountered, the surgeon must clearly describe whether it was removed en bloc, in more than one piece, and if residual thrombus was thought to be left behind.

Neuroblastoma Power Notes [1]

Where do neuroblastic tumors (NBT) arise from?
They arise from the sympathetic cells of the neural crest. Thus NB can occur in sympathetic ganglia, sympathetic para-ganglia, or adrenal gland.

How is NB differentiated from other small round blue cell tumors?
The histopathologic findings characteristic of NB are:
1. Rosettes: NB cells surrounding neural fibrils
2. Neuropil: neuritic processes
3. Schwannian cell stroma: reactive/non-neoplastic tissue, recruited by tumor cells, and composed mostly of sheets of spindle cells. Schwannian stroma has an antineoplastic/anti-angiogenic/pro-differentiating effect on NB cells. The amount of stroma present is the major factor that divides neuroblastic tumors into NB vs. ganglioneuroblastoma and ganglioneurooma. More Shwannian stroma imparts better prognosis

What is the Shimada classification and what is it based on?
The Shimada classification is an age-linked histopathologic classification that is used to divide neuroblastic tumors in to favorable and unfavorable histology groups. It depends on
1. Degree of cellular differentiation
2. Mitotic-Karyorrhectic index: Number of cells in mitosis or Karyorrhexis (cell death) per 5000 cells. MKI can be low (<100), intermediate (100-200), or high (>200).
3. age
4. Amount of Shwannian stroma
The Shimada classification has independent prognostic value, where FH tumors have a 90% 5 year EFS, and UH tumors have a 30% 5 year EVS.

How is the International Neuroblastoma Pathologic Classification (INPC) different from the Shimada classification?
The INPC is based on the Shimada classification. It divides neuroblastic tumors into 4 tumor categories under 2 distinct prognostic groups: favorable subgroup (FS) and unfavorable subgroup (US).
FS:
Ganglioneuroma differentiating
Ganglioneuroblastoma intermixed type
Ganglioneuroblastoma nodular (with specific favorable features)
US:
Ganglioneuroblastoma nodular (unfavorable features)
Neuroblastoma

What is the histopathologic definition of NB?
NB is a Shwannian poor neuroblastic tumor (<50% Schwannian stroma) divided into three main types 1. Undifferentiated: No neuropil present 2. Poorly differentiated: <5% cells showing signs of differentiation into ganglion cells and neuropil present 3. Differentiating: >5% cells showing signs of differentiation and neuropil present

What defines Ganglioneuroblastoma (GNB) and Ganglioneuroma (GN)?
GNB and GN are both Schwannian stroma rich neuroblastic tumors (>50%)

What are the characteristics of GNB?
GNB cells are progressing into mature ganglion cells with >50% of cells in the maturing form (not completely mature, otherwise would be ganglioneuroma). GNB has residual foci (vs scattered) of neuroblastic cells that constitute <50% of cells. GNB is divided into the intermixed type (GNB-I) (where the foci of neuroblastic cells are microscopic) and the nodular type (GNB-N) (where foci are macroscopic) The GNB-I type are considered under the favorable subgroup while the GNB-N can be either favorable or unfavorable subgroup based on INPC factors [2] What are the characteristics of GN?
GN divided into GN mature (composed of mature cells and no neuroblastic elements) and GN maturing. The GN-maturing contains scattered (vs. foci) differentiating neuroblastic cells. Unlike GNB, these cells do not form distinct foci.

What is Horner's syndrome?
Horners syndrome results from loss of sympathetic innervation to part of the face. It consists of:
1. Ptosis: drooping of the eyelid due to loss off innervation of the upper tarsal muscle
2. Mioisis: small pupil
3. Anhydrosis: Decreased sweating on the affected side of the face
4. Enphthalmos: Impression that the eye is sunken
5. Heterochromia (in children): due to decreased melanin pigment deposition in the pupil on the effected side, secondary to loss of sympathetic innervation

What is acute cerebellar ataxis?
Also referred to as the 'dancing eyes syndrome', usually occurs in infants with mediastinal masses and results from excessive catecholamine production
It consists of:
1. Myoclonus: brief, involuntary twitching of muscles
2. Opsoclonus: uncontrolled eye movement
3. Nystagmus

Where are NB's usually found?
Adrenal gland (50%), Paraspinal ganglia (25%), Thorax (20%), pelvis (4%), and neck (1%)

Where does NB metastasize to?
40% of NB are stage 4 (metastatic) at time of diagnosis. Metastasis is most frequently to bone (bone pain), Bone marrow (anemia), and lymph nodes.
Raccoon eyes result from retrobulbar venous plexus spread.

What is stage 4S NB?
A specific type of metastatic NB found in infants (<1 year). Primary tumor is localized (stage 1, 2A, or 2B) and spread is limited to: 1. Skin: blueberry muffin lesions 2. Liver: can cause respiratory distress from hepatomegaly 3. Bone marrow: malignant cells should be limited to <10% nucleated cells. Can cause anemia. What are the different options for diagnosis of NB?
1. Histopathology of primary tumor OR
2. Tumor cells in bone marrow + elevated urine catecholamines

What laboratory values correlate with NB tumor burden?
1. LDH
2. Catecholamines
3. Neuron specific enolase
4. Ferritin

How often are calcifications found on CT scan?
85% of cases

In what setting is MRI better than CT scan for NB imaging?
1. evaluation of stage 4 disease: Bone and bone marrow metastatic disease
2. evaluation of encroachment into neural foramen
3. evaluation of vessel encasement

What is MIBG scan and how does it work?
MethIodoBenzylGuanine is taken up by the storage granules in chromaffin cells, in the same way catecholamines are. Detects the primary tumor, involved LN's, and metastatic disease.

What is the main drawback of INSS and how is that counteracted?
The main drawback is the the staging and thus the prognosis is dependent on extent of resection, and thus the skill and aggressiveness of the surgeon. Image defined risk factors, those that preoperatively predict worse prognosis, can help provide a more uniform system for staging disease at presentation.Such factors include vessel encasement, extension into neural foramena etc...

What are the two main categories of determinants of prognosis?
1. Clinical factors: age and stage
2. Biological factors: NMYC, DNA plyody (in infants), histopathologic classification (Shimada)
additional variables include LOH: 1p or 11q deletions. Loss of tumor suppressor genes. Used to define duration of chemotherapy in some situations.

What is the probability of 5 year disease free survival?
Low risk group > 95%
Intermediate risk group > 90%
High risk group < 30% What role does partial tumor resection play in NB?
As long as there is no N-MYC amplification, >50% resection of localized tumors (including stage 2 disease) keeps patients in the low risk group.

What is the adjuvant therapy for low risk disease?
Low risk disease is observed after resection, except in the situation where less than 50% of the tumor was resected or in the presence of organ or life threatening symptoms.

When is 4S disease considered intermediate risk?
when symptomatic, has unfavorable biologic characteristics (by Shimada/INPC) or DNA index=1, or when no tissue is obtained for evaluation.

What chemotheraputic agents are used for intermediate risk disease?
cyclophosphamide, doxorubicin, carboplatin, etoposide.
Patients with favorable histology receive 4 cycles, unfavorable histology receive 8 cycles (each three weeks apart).

What is the current COG protocol goal for intermediate risk NB?
Protocol ANBL0531: Aims at reducing chemotherapy by decreasing the number of cycles.

What are the main chemotherapy strategies for high risk NB?
1. combination of agents to decrease resistant tumor growth and improve synnergy
2. use of maximal tolerated dose/high dose intensity
3. Target therapy for minimal residual disease
for autologous BM transplant, cells are harvested after second cycle of chemotherapy.
after neo-adjuvant therapy, resection re-evaluated after 5th cycle

What is the current COG protocol for high risk NB?
Protocol ANB0532: looks at role of further intensification of myoablative therapy, effect of radiation on residual and metastatic disease, test the effect of dose-intensified topotecan containing induction therapy.

How is response to therapy assessed?

1. volume (radiologic)
2. urine catecholamine levels
3. MIBG scans

Who are the patients who undergo surgical therapy alone without adjuvant therapy?

Most localized tumors with favorable histology:
stage 1 tumors
stage 2 A/B with no N-MYC amplification and >50% resection
stage 3 midline tumors completely resected with negative nodal disease

When is LN assessment not important in NB?

LN involvement in thoracic neuroblastoma does not affect risk classification, despite potential effect on staging

References: (Ashcraft textbook unless otherwise specified):
1. Ashcraft's Pediatric Surgery. 5th Edition. Chapter 68: Neuroblastoma
2. Okamatsu et al. Clinicopathologic characteristics of ganglioneuroma and ganglioneuroblastoma: A report from the CCG and COG. Pediatr Blood Cancer (2009) 53:563-9

4 mechanisms of esophageal injury by button batteries

Coins, the most commonly encountered ingested foreign body in children, cause complications related to chronic impaction and erosion. Button batteries are more dangerous. Methods by which they can cause damage (mostly when stuck in the esophagus) include

1. Toxic effect of mercuric oxide: some batteries contain lethal levels of mercuric oxide (5g). Batteries containing other heavy metals, lithium, or manganese are not toxic.
2. Electrical discharge from the battery
3. Pressure necrosis (as with coins)
4. Caustic injury from leakage of the battery's contents

Interestingly, batteries smaller than 1.6cm in diameter do not get lodged in the esophagus. Restricting the size of batteries produced to less than 1.6cm may help prevent serious injuries that can occur in as little as 5 hours after ingestion.

Reference:
Yardeni et al. Severe esophageal damage due to button battery ingestion: can it be prevented?
Pediat Surg Int (2004) 20:496

Variation in resource utililization associated with the management of appendicitis in children (APSA2011)

This presentation shed light on the spectrum of hospital costs entailed by different institutions for a somewhat uniform disease process, simple appendicitis, and the more heterogenous form, complicated or perforated appendicitis.

Not surprizingly, the authors found a significan variation in resourse utilization between institutions. This included the use of imaging studies and laboratory tests, readmission rates for both simple and complicated appendicitis, and hospital costs. Most strikingly, the authors noted an adjusted, case-related hospital cost for simple appendicitis that ranged from $4,000 to $10,000. As to complicated appendicitis, the cost ranged from $6,000 to $27,000.

Despite the limitation of studies obtained from databases, and the lack of correlatio between resource utilization and outcome, this study highlights the marked variability in management of a common condition that results in substantial resource utilization.

Why does simple appendicitis cost $4K in one hospital and $10K in another. Is the answer as simple as using cheaper but equally effective instruments? And if so, should we not all be standardizing this operation to help save what seems to me to be a lot of money?

Reference:
Variation of resource utilization associated with the management of appendicitis in children: implications for quality improvement through comparative analysis and collaborative networking.
Rangel SJ, Baxter J, Barnes J.