Vascular lesions: time to abandon the nomenclature of edibles!

After a long conversation discussing the management plan for a “giant cavernous hemangioma” of the liver, and although I had just recently brushed up on the subject of vascular lesions, I had to go back and look it up again. I was pretty sure the term “cavernous hemangioma” was as antiquated as “strawberry hemangioma” or “port wine stain”; the generalized agreement around me on the diagnosis made me doubts myself. Back to the books.

Sure enough, as of 25 years ago, the International Society on the Study of Vascular Lesions adopted the Mulliken system of classification, which divides vascular lesions into tumors (mainly infantile hemangiomas) and malformations (capillary, venous, lymphatic malformations etc…). This division is based on clinical and histologic characteristics; vascular tumors display endothelial proliferation and usually regress with time, while vascular malformations have a quiescent epithelium, result from dysmorphogensis of vessels, and tend to enlarge with time.

No more should the term lymphangioma, which by vertue of the –oma suffix suggests a tumor, be used to describe a lesion that is a malformation (lymphatic malformation). Nor should the term cavernous hemangioma be used to describe what could either be a deep visceral hemangioma or a venous malformation (two distinct entities, treated in very different ways).

A study by Hassanein et al reviewed articles on vascular lesions and noted a 70% incidence of incorrect nomenclature and a subsequent 20% incidence of incorrect treatment based on erroneous classification. They commented that this is probably an underestimation of the incidence of incorrect diagnosis and treatment in clinical practice, given that experts had probably edited many of these articles for accuracy.

Another reason we should continue to read, read, and read some more.

Reference:
Hassanein et al. Evaluation of terminology for vascular anomalies in current literature. Plastic and Reconstructive Surgery (2011);127(1):347

What is the normal length of small bowel in a preemie?

After informing a dad that his preemie baby has only 45 cm of small bowel left after surgery for NEC, he asked me a question that caught me off guard.
“So how much should he have at 27 weeks gestation?”
Knowing that the small bowel almost doubles in length at the last trimester, I estimated 100 cm’s but then headed back to the books/PDF files to figure out a more exact answer.

Fortunately, there had been some back and forth emails between two of my attendings about papers that looked into expected bowel lengths for preemies.
Went home, pulled the emails out of my ‘Educational’ folder in ‘Mail’, transferred the PDF’s to my ‘Papers’ software, synced my MBP with my iPad (go paperless!), then read the articles during my 45 post-call spin session.

In the first article (via Dr Philip Glick), by Touloukian et al, the authors measured the length of small bowel obtained from autopsy specimens of 30 babies of various gestational ages. The authors documented the bowel length over three age ranges and noted that the small bowel more than doubled its length during the third trimester. As attractive as this article is in its simplicity, several confounding factors, including the fact that post mortem changes may affect the measured length of bowel, limit the accuracy of these bowel measurements.

In the second article, published more than 30 years later (via Dr Doruk Ozgediz), by Strujis et al, the authors obtained intraoperative measurements of small bowel in 108 patients whose post conceptual age ranged from 24 weeks to 5 years. The authors linked the bowel length to gestational age, weight, and patient length at time of surgery. They noted that all three variables predicted the length of bowel with similar accuracy, and suggested that patient height be used since it is more consistent and easier to measure.

Why is this important? Knowing the expected normal length of bowel in a preemie baby makes estimations of the potential risk of short gut syndrome and other outcomes, after intestinal resection, easier; this helps better council parents. It also helps answer the question: "Well, how much bowel should my baby normally have?”

References:
1. Touloukian RJ, et al. Normal intestinal length in preterm infants. Journal of Pediatric Surgery (1983) 18(6):720
2. Strujis M, et al. Establishing norms for intestinal length in children. Journal of Pediatric Surgery (2009) 44:933

Take notes in the OR

At the pediatric surgery residents’ meeting at the AAP last week, one of the speakers, a new graduate who was scheduled to discuss strategies for negotiating an academic job, started off with completely unrelated, but precious advice for residents: read about your patients (and don’t just study for the boards), go to clinic (many pilomatrixomas will be seen in your office), and take notes in the OR. How is it that, as residents, many of us go through training without ever documenting, in our own words, what we are taught in the OR?!

I’m not sure whom I should give credit to for giving me this same advice at the time, but I have been taking notes in the OR since I was a third year resident. And when I say notes, I mean detailed accounts of the main steps, instruments used, suture etc…. I have two notebooks, one from general surgery residency and one from my current pediatric surgery training, filled with elaborate step-by-step instructions. Details about specific preoperative studies, how to prep and drape (attending specific!), exact instruments to use and at what point to switch, post operative management pathways, and follow up plans.

Writing notes helped me focus on and analyze the steps of an operation. I frequently found myself unsure of which step came first or which retractor was used for a specific exposure. The more notes I wrote, the more I paid attention to details I had missed before. I even found myself watching an operation just to be able to fill gaps in my operative notes when there was a step I could not recall.

When I started taking notes and reviewing them preoperatively during my general surgery training, I could not help but notice how positively my attendings reacted to the fact that I prep’d and draped EXACTLY as they did (detailed notes!). Prep right, ask for the exact suture and instrument, and you would be amazed how much more autonomy you may be given.

Those little gems that are mentioned in the OR that you cannot find in any textbook, many of which are the culmination of years of experience, should all be jotted down on the margins of the page next to the detailed list of steps.
“This is where you need to slow down and take your time along this corner, and switch the traction with your left hand to help with exposure” is not something you can find in an atlas, but something that should be written in permanent black ink next to a sketch or diagram.

Unlike a surgical atlas, my own account of how I learned to do a Nissen or a hernia repair will be much more relevant and useful to me when the time comes for me to do the same operation and ask for the next suture or retractor. There will be no time spent scratching my head when the scrub tech asks me what suture I want to close the diaphragmatic defect with or figure out what size clip I need for the PDA ligation. If I had not been taking notes, I might have not remembered that there was such a thing as a M-L clip (green); a clip that is smaller than the Large (orange) which can be too large, and larger than the Medium (blue) that can be too small. Something that would be great to know ahead of time when a preemie’s chest is open and no clip seems to be the correct size!

As a bonus, at the end of my general surgery residency, I asked my favorite attendings to review the notes I took of their operations, correct them as they wished, and sign them as a souvenir. Now, on my bookshelf, I have two of my most precious references and souvenirs from training. I guard them with my life!

What is the 'leading edge' of a transition zone in Hirschsprung's disease, and why is it important?

Time to dip into the old stash for an interesting paper. This one was out of St Louis, MO and looked at the properties of the transition zone of ganglion cells in HD by taking sequential cross sections of surgical specimens and quantifying the ganglion cells in the submucosal and myenteric plexus.

The authors noted that the transition zone was not uniform, but instead had a leading edge (analogous to dripping paint). This leading edge of the transition zone was measured to be up to 2.1 cm (average 1.1 cm) and 2.4 cm (average 1.4 cm) long in the submucosal and myenteric plexuses, respectively. Additionally, the number of ganglion cells at the tip of the leading edge was normal.

The significance of this finding is that a frozen section biopsy performed at the transition zone may result in a pull-through that includes abnormal bowel and potentially poor functional results. The authors thus recommended that a pull-through be performed using bowel that is at least 2 cm proximal to the area of 'normal' ganglionated bowel identified intraoperatively by frozen section

Reference:
White et al. Circumferential distribution of ganglion cells in the transition zone of children with Hirschsprung's disease. Pediatric and Developemental Pathology (2000) 3, 216

What to do with a child in the ED after a household electrocution?

So a kid gets bounced around hospitals before being sent to our ED for admission. Shortly after, we send the kiddo home with some local wound care to a blister.

Low voltage electrocution (<1000 volts) is a common household injury that is usually a result of contact with electric cords and wall outlets. One of the main concerns with electrocution is related to cardiac consequences, specifically ventricular fibrillation and direct myocardial injury.

Chen et al reviewed the literature pertaining to the management and outcome of children exposed to a low voltage current (usually household appliances with a maximal voltage of 240V). They summarized the results of 7 retrospective studies that evaluated the relationship between the type of voltage, patients symptomatology at the scene (cardiac arrest, ventricular fibrillation), EKG findings (when an EKG was performed), and patient outcome.

The upshot of the review article was that healthy children who are exposed to household currents, when asymptomatic at the field and in the ED, had a very low risk of developing cardiac arrhythmias. When the children did have 'benign' arrhythmias (mainly sinus tacchycardia, vernticular premature complexes, and premature junctional complexes), those resolved spontaneously. Children who did not have abnormal EKG findings never developed any late arrhythmias.

The authors concluded that it is safe to discharge asymptomatic children exposed to household currents without and EKG or telemetry.

Reference:
Chen EH, Amit S. Do children require ECG evaluation and inpatient telemetry after household electrical exposure. Annals of Emergency Medicine 2007;49:64-67

Pediatric Liver Tumors Power Notes [1]

What is the age range of children with hepatoblastoma (HB) vs. hepatocellular carcinoma (HCC)?
HB is most common between the ages of 6 months and 3 years, while HCC occurs in older children and adolescents.

What is the origin of HB?
HB arises from pluripotent hepatic stem cells or oval cells that can differentiate into hepatocytes or biliary epithelial cells.

What conditions is HB associated with?
Beckwith-Wiedemann syndrome
Hemihypertrophy
Low birth weight
FAP

What proportion of liver tumors are malignant?
2/3

What % of patients with HB have thrombocytosis?
60%

What is the most sensitive blood test to evaluate for HB and HCC?
AFP: produced by fetal liver cells and yolk sac. In neonates, levels are normally elevated and then drop to adult levels by age 6 months.
AFP is elevated in 90% of children with HB, and 70% of those with HCC
AFP levels are not associated with the level of maturity of HB

What other conditions cause elevated AFP levels?
Liver cirrhosis
Hepatitis
Germ cell tumors
Hemangioendothelioma
Testicular tumors
Gall bladder CA

Which variant of HCC is not associated with elevated AFP levels?
Fibrolamellar HCC

What should we look for when imaging for liver tumors?
Size/location of tumor
Metastatic disease
Vascular invasion to PV, HV, and VC

What is the advantage or MRI?
MRI is accurate in determining the relationship of the tumor to vascular and biliary structures.
Tumors appear homogenous and hypointense on T1 sequences, and hyperintense on T2 sequences.

Is FNA biopsy an option with liver tumors.
Yes, FNA may be sufficient to confirm the diagnosis.

What are the benign liver tumors?
Benign vascular tumors
Mesenchymal hamartoma
Adenomas
FNH

What is the role of HB histology in prognosis?
The histology of HB has minimal impact on prognosis.

What is the histologic classification of HB?
Epithelial vs. mixed (epithelial + others)
Epithelial divided into: Fetal, embryonal, macrotunular, and small cell undifferentiated.

What from of HCC has a better outcome than the typical variants?
Fibrolamellar variant

What is the COG staging system based on?
Post resection extent of disease.
Stage !: completely resected. Purely fetal histology (PFH) with minimal mitotic figures is unique group
Stage 2: microscopic residual disaese
Stage 3: gross residual disease
Stage 4: metastatic disease

What is unique about the PFH group?
When completely resected, patients with PFH and low mitotic figures (<2/10 mitotic figures) have excellent outcomes and do not require adjuvant chemotherapy. This situation occurs in 5% of patients with HB. What are factors that can compromise surgical resection?
Multifocality, bilobar involvement, portal vein or vena cava thrombosis, para-aortic lymphadenopathy, extension into liver hilum, and metastatic disease.

Why should a smaller incision be used initially?
A smaller incision should be used first to assess resectability before committing to a larger incision.

How should microscopically positive margins be managed?
Re-excision if possible.

Why should intraoperative U/S be used?
Intraoperative U/S should be used to better assess vascular involvement.
The most common cause of complications such as positive resection margins, severe intraoperative hemorrhage, and post operative liver failure secondary to Budd Chiari syndrome is unrecognized involvement of the remaining solitary hepatic vein.

What are options for anatomic resection?
R or L hepatic lobectomy
Extended R or L hepatic lobectomy
Central resection
Segmental based anatomic resection (rare)

What are the basic steps for resection?
Check for metastatic disease
Mobilize liver
Dissect poratal structures
Ligates structures supplying intended segment of liver to create line of demarcation
Dissect VC off the liver towards the VC, leaving hepatic veins as only attachment
Ligate hepatic veins within parenchyma of liver vs. extra-hepatic segments.
Perform parenchymal dissection

What is the max time allowed for clamping of portal structures?
60 minutes total, 15 minutes at a time.

What is the name of the imaginary line between GB and IVC?
Median portal fissure.

How much of the liver is removed with a L lobectomy vs a R lobectomy?
A L lobectomy removes 35% of liver parenchyma while a R lobectomy removes 65%.

What are potential postoperative complications?
Bleeding, subphrenic abscess, biliary fistula, wound infection, and biliary obstruction.
Perioperative mortality is 5%.

Why are neonates more susceptible to complications of liver resection and how is that counteracted?
Neonates have immature livers and are susceptible to postoperative hypoalbuminemia, hypoglycemia, and hypothrombinemia.
Perioperative administration of vitamin K, albumin, and vitamin K can counteract these deficiencies.

what % of HB will require liver transplant?
6%

What is the contra-indication to liver transplant in HB?
Extrahepatic disease

What are 10-year survival rates after primary transplant vs. rescue transplant (after attempted resection)?
Primary transplant has 85% 10-year survival, vs. 30-50% with rescue transplant.

When is transplant indicated for HCC?
Single lesion <5cm or up to three nodules < 3 cm. What are the disadvantages of neo-adjuvant chemotherapy?
Non-responders may experience disease progression.

What are agents used for initial therapy vs therapy for non-responders/recurrent disease?
Baseline therapy is with Cisplatin/Vincristine/5-FU or Cisplatin/Doxorubicin.
Resistant or recurrent disease is treated with etoposide/carboplatin or irinotecan

How often are unresectable tumors rendered resectable by neo-adjuvant therapy?
up to 70% of stage 3 tumors become resectable with neo-adjuvant therapy.
Only 30% of HCC are rendered resectable with neo-adjuvant therapy.

What is the role of radiation in liver tumors?
Radiation has a limited role. Not very effective.

What is suicide gene therapy?
Therapy that selectively targets tumor cells, where a non-toxic, cell permeable pro-drug, is converted to a toxic drug inside tumor cells only.

What are available options for ablative therapy?
Patients who are not candidates for transplant or resection can undergo ablative therapy.
Options incllude:
1. Chemo-embolization
2. RFA: Needle electrode delivers heat through an alternating current
3. Percutaneous injection of alcohol
4. Cryoablation: direct freezing then thawing results in cell death.

What are U/S findings that help guide ablative therapy?
RFA: echogenic micro-bubbles delineate the zone of therapy
Cryoablation: echogenic expanding rim

What is 5 year survival of HB vs HCC?
75% for HB vs 30% for HCC

What is 5 year survival with successful resection?
up to 100% for HB vs 54% for HCC

What is the primary predictor of poor prognosis?
Metastatic disease

What is the role of lung metastectomy?
Only lung lesions that do not respond to neoadjuvant chemotherapy should be resected

Reference:
1. Grosfeld's Pediatirc Surgery. Sixth edition. Chapter 30. Liver Tumors

Is this neonatal small left colon syndrome (NSLCS) and what's the next step?

This kiddo read the book before
he was born!

Mom with maternal diabetes. 24 hour old baby born term, had bowel movement only with stimulation, and then started having bilious emesis. Exam and AXR were consistent with a distal bowel obstruction. UGI to r/o malrotation showed a normally located ligament of Trietz, while the contrast enema showed a small left colon with a transition point at the splenic flexure (above).

Dilemma!... Given the kid's history and the imaging findings, this is very likely NSLCS. But do we not need to be sure we're not missing Hirschsprung's disease?

Time for some PubMed action and an article titled: "Neonatal small left colon syndrome in the offsprings of diabetic mothers-an analysis of 105 children". Perfect!

In this article by Ellis et al, the authors looked at 105 patients born to mothers with diabetes in pregnancy (pregestational or gestational). Of these neonates, 6 had intestinal obstruction. 5 had NSLCS and one had Hirschsprung's disease (recto-sigmoid transition zone). The obstructive symptoms in the neonates with NSLCS resolved after a contrast enema.

The authors emphasized that 50% of infants born with NSLCS are born to mothers with diabetes during pregnancy. Additionally, when such infants are born with distal intestinal obstruction, the chance of having NSLCS vs. Hirschsprung's disease is >10:1. Given that NSLCS is a self limited disease that resolves with a diagnostic/theraputic contrast enema, it would seem reasonable to treat this baby expectantly, and perform a rectal biopsy if he does not resume a normal pattern of bowel function.

Reference:
Ellis H, Kumar R, Kostyrka B. Neonatal small left colon syndrome in the offsprings of diabetic mothers-an analysis of 105 children. Journal of Pediatric Surgery (2009)44,2343-2346

Cervical seat belt sign in kids. What are the implications?

Three trauma alerts. Three kids in an MVC.
Three cervical seat belt signs. Now what?

After obtaining a CT-arteriogram on all three (no injuries) it was time to dig up that paper I came across a couple of years ago.

This paper, out of Emory University, looked at cervicothoracic seatbelt signs (SBS) and their association with vascular injury. The authors prospectively studies the results of their workup algorithm for SBS's, which consisted of an arteriogram or CTA for all patients with cervical SBS and those with a thoracic SBS who were symptomatic or suspected of having an aortic injury.

They identified 131/797 (16.4%) of trauma patients with a cervical and/or thoracic SBS, 3% of whom were found to have a vascular injury (mortality 50%).

Of the pediatric patients in that study, all of whom were appropriately restrained, 18.8% had a SBS. None of those patients had a vascular injury.

This study basically validated the safety of an algorithm where all patients with a cervical SBS undergo either a CTA or arteriogram (emergently in the presence of an abnormal neurovascular exam or GCS<14), while only those with a thoracic SBS and an abnormal neurovascular exam need further imaging (the rest should be ovserved and reexamined).

Interestingly, 2 of the 4 patients with carotid injury had an isolated thoracic SBS, suggesting the importance of shearing forces related to deceleration and hyper extension/flexion in carotid injury.

The absence of vascular injury in the pediatric population in this study should obviously not be considered a reason not to continue to image these patients, given that the number of pediatric patients in this study was small, and the potential consequence of missing an injury (rare as it is) is catastrophic.

Reference:
Rozycki et al. A prospective study fro the detection of vascular injury in adult and pediatric patients with cervicothoracic seat belt signs. The Journal of Trauma injury, infection, and critical care (2002) 52:618-624

Wilm's Tumor Power Notes [1]

What was Sidney Farber's contribution to the field of oncology?
Sidney Farber was the first to us adjuvant chemotherapy (Actinomycin D) to treat cancer (Wilm's tumor).

What syndromes is WT associated with and how often?
In 10% of cases, WT is associated with:
1. sporadic aniridia
2. isolated hemihypertrophy
3. Denys-Drash syndrome
4. genital anomalies
5. Beckwith-Wiedemann syndrome
6. WAGR (60% develop WT)

What are the main genes associated with WT, and what is the role of the protein produced by those genes?
WT1 and WT2 (reside on chromosome 11) are tumor suppressor genes that code for proteins that suppress growth inducing genes. Deletions in WT1 and WT2 predispose to WT.
WAGR is associated with WT1 and Beckwith-Wiedemann syndrome is associated with WT2

How often is WT bilateral in WAGR?
60% of patients with WAGR develop WT which is bilateral in 17% of cases

What is the relationship between Beckwith-Wiedemann syndrome and WT?
Kids with BW syndrome have a 40% chance of developing WT

How often is WT familial?
in up to 2% of cases

How does loss of heterozygosity (LOH) affect prognosis?
LOH (of chromosomes 1 or 16) is associated with increased risk of relapse and mortality.
LOH-16 present in 15-20% of WT, LOH-1 present in 10%

What is screening protocol for patient with syndromes associated with WT?
Ultrasound of kidneys every three months until the age of 5 YO

What are nephrogenic rests (NR) and what are their two distribution patterns?
NRs are persistent metanephric tissue beyond 36 weeks of gestation. The vase majority of NRs involute. They are found in two main distribution patterns.
1. Perilobular (PLNR): more common
2. Intralobular (ILNR)

What is the autopsy incidence of NRs?
~1%
PLNR: 0.9%
ILNR: 0.1%

What are the three histologic groups of NRs?
1. Incipient (infants)/Dormant (Older children): composed of blastemal and primitive epithelial cells that resemble embryonic kidney tissue and WT, but are microscopic and have sharp margins.
2. Regressing/Sclerosing (most common): show maturation of cellular elements. Progress to become obsolete rests composed of hyaline stromal elements (acellular proteinaceous material).
3. Hyperplastic: These are difficult to distinguish from WT, except based on architecture. They have uniform growth components that result in enlargement of the entire rest (preserving it's shape), as opposed to the neoplatic growth (WT) that results in a spherical expanding nodule within a rest.

How are hyperplastic NRs differentiated from WT?
The shape of the NR is preserved in hyperplastic NRs, and there is now surrounding pesudocapsule (which is found in WT). The importance of architectural characteristics makes a needle biopsy insufficient for differentiation unless they contain a part of the lesion's margin.

What is the association between WT and NRs?
41% of unilateral WT have NRs vs 99% of bilateral WT. NRs are increased in patients with WT associated with syndromes.

What is diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and what is it's radiologic characteristic?
DHPLN is an entity that can be confused with WT. Infants with DHPLN have unilateral or bilateral enlarged kidneys that maintain their their normal shape and lack necrosis. DHPLN can become WT (in ~50% of cases despite neoadjuvant chemotherapy) so they should be monitored closely. Changes in CT/MRI characteristics or evidence of growth of DHPLNs should raise concern for WT.

what is the treatment and prognosis of DHPLN?
Chemotherapy is used to decrease the size of DHPLNs, which may cause respiratory compromise by virtue of their size, but has not been shown to decrease the risk of malignant transformation. 100% transformation to WT in the absence of chemotherapy, vs 55% when biopsy/chemotherapy performed.
A high proportion of patients with DHPLN and WT will have anaplastic WT

Is nephrectomy justified in multicystic dysplastic kidneys?
No. Only 4% of these patients will have NRs and the risk of WT too low to justify prophylactic nephrectomies

What defines unfavorable histology WT (UH)?
Presence of focal or diffuse anaplasia. Anaplastic cells have large, pleomorphic, hyperchromatic nuecleii with abnormal mitotic figures. Focal anaplasia confers a better prognosis than diffuse anaplasia. Anaplasia is aassoicated more with respnse to therapy than tumor aggressiveness.

What are the two tumors that were considered WT UH and where split into a different category?
Clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumors

What is the main difference between NWTSG and SIOP classifications?
NWTSG is a pre-treatment staging system while the SIOP assesses post treatment characteristics of the tumor.

What difference between Stage II and Stage III in terms of spillage?
Spillage is now considered Stage III regardless of whether it is local or diffuse, from a biopsy or tumor rupture. The extent of spillage affects the field of radiation given. Local spillage in the renal fossa is treated with local flank radiation; spillage outside the tumor bed mandates total abdominal radiation [2]

Is there a difference in terms of gross or microscopic post resection residual tumor in terms of staging?
No. Both are considered Stage III

How are tumors classified into risk groups based on neoadjuvant chemotherapy?
Based on histology at resection AFTER neo-adjuvant chemotherapy.
Low risk tumors are those that are completely necrotic (>99%)at time or resection
Blastemal predominant tumors (high risk) are those with more than 1/3 of tumor viable, and at least 2/3 of the viable tumor consists of blastemal cells.
Intermediate risk tumors are those with a variety of histologic charactaristics in between the low and the high risk categories.

What are the main pathologic characteristics of WT and how are they related to outcome?
WT is an embryonal neoplasm with blastemal, stromal, and epithelial components. Each of these can have variable levels of differentiation, including anaplasia.

What is particular about fetal rhabdomyomatous nephroblastoma and diffuse blastemal type WT?
Both these subtypes of WT. Fetal rhabdomyomatous nephroblastoma has poor response to chemotherapy, but excellent prognosis. Diffuse blastemal type has rapid response to chemotherapy, but characteristically presents with advanced disease

Which kids are at risk for anaplastic WT?
Kids older than 2 YO. Mortality from anaplastic WT ~ 60%. Outcome better for focal vs diffuse anaplasia.

What is the rate of metachronous contralateral disease and what are risk factors?
The rate of metachronous disease is 1% (synchornous is 5%). This is increased:
1. In the presence of NRs
2. Kids younger than two years
3. associated syndromes

What are the main characteristics of clear cell sarcoma of the kidney?
metastasis to bones and brain. Unclear cell origin

What are the main characteristics of malignant rhabdoid tumors of the kidney?
average age 11 months
characteristic involvement of perihilar renal parenchyma
second primary neurglial tumor in the brain

What are the main chemotheraputic agents used with WT?
Dactinomycin, vincristine, doxorubicin

When is doxorubicin added?
Stage III disease or in the presence of anaplasia

What are the aims of the main SWTS studies?
SWTS3: Use of Dox for Stage III dz
NWTS4: Dose intensification (less frequent) adequate with less hematologic toxicity
NWTS5: Effect of LOH on outcome in stage 1 and 2: decreased EFS
looked at management of relapse

What chemotheraputic agents are used for anaplasia?
Focal anaplasia: Vincristine/Dactinomycin/Doxorubicin
Diffue anaplasia: add cyclophosphamide +/- etoposide


What agents are used for CCSK and malignant rhabdoid tumors?
CCSK: Doxorubicin
Malignant rhabdoid: cyclophos/carbaplatin/etoposide (non of the basic WT agents)

What are the disadvantages of the routine use of neoadjuvant chemotherapy (SIOP)?
1. risk of losing staging information
2. risk of treating benign disease
3. modification of tumor histology by chemotherapy
4. Clear cell/rhabdoid will not respong
up to 10% rate of benign or altered malignant diagnosis in kids with pre-nephrectomy diagnosis of WT

What are the complications of doxorubicin?
1. cardiomyopathy in 1.2%
2. secondary malignancies (AML) in 1.6%

What are risk factors for a secondary malignancy?
1. doxorubicin
2. irradiation
3. prior treatment for relapsed tumor

What are the current guidelines for radiation therapy to lungs?
low dose radiation if lunges involved.

What is the significance of CT only lung lesions? [3]
Up to a third of lung lesions found on CT in patients with WT are not malignant.
Patients who are stage I or II FH WT should undergo biopsy of CT only lesions to gauge therapy. Those who are FH stage III or IV who are on AREN0533 protocol trial receive chemotherapy and then are reevaluated after 6 weeks. At that time, any residual lesions will get radiation, preferably after biopsy

What are guidelines for abdominal irradiation? [2]
Local Stage III disease. 10cGy


What are the main things that need to be assessed on imaging?
1. contralateral kidney involvement
2. two functioning kidneys
3. vascular involvement

What is the incidence of synchronous contralateral lesions?
5%

Is there a need for contralateral exploration and why?
No. Although 10% of lesions on the other side may be missed by imaging, these lesions do not affect outcome and recurrence, especially that some are NRs and not WT.

What are the false positive and false negative rates of clinical assessment of LN involvement?
The false positive rate of clinical assessment is ~20% and a false negative rate is 30%. Thus routine sampling of LN's (even when not suspicious) is mandatory for proper staging.

Why is cystoscopy important in the presence of hematuria?
Cystoscopy is important to rule out tumor extension into the bladder, where cutting through the ureter would result in cutting through the tumor, thus upstaging the patient.

What are factors related to increased risk of tumor recurrence?
Stage III
Intraoperative rupture
Anaplasia

What are indications for neoadjuvant chemotherapy (NWTSG)?[2]
1. solitary kidney
2. bilateral tumors: all bilateral tumors are treated with upfront chemotherapy. Any attempts at partial nephrectomy should be with held until week 6 or 12 [2]
3. horseshoe kidney
4. unresectable tumor
a.intravascular extension of tumor thrombus above hepatic veins
b.involvement of contiguous structures that would need to be sacrificed
c.if resection risks unnecessary morbidity and mortality per surgeon judgement
d.pulmonary compromise due to extensive pulmonary metastasis
5. respiratory distress form mass

Should both kidneys be biopsied in bilateral WT? [2]
No. Initially, and because of the risk of discordant pathology between the two kidneys, it was recommended that both kidneys be biopsied.
Per new COG protocol, renal biopsy is not necessary in stage V disease. Protocol calls for upfront 3 drub chemotherapy followed by possible OPEN biopsy (<50% reduction in size which may suggest presence of anaplastic tumor) or resection (tumor rendered resectable) or continued chemotherapy and resection at 12 weeks When is a core needle biopsy vs an open biopsy acceptable?
A core needle biopsy is acceptable to obtain a tissue diagnosis when a suspected WT tumor is deemed unresectable. An open biopsy is mandatory in the setting of bilateral WT that does not decrease in size by more than 50% after 6 weeks of chemotherapy.

How often is intravascular extension identified?
The renal vein is involved in 11% of children, the vena cava in 5% [2]. The Renal vein and VC should be palpated for the presence of tumor intraoperatively, even when preoperative imaging studies are normal.

Which patients are candidates for resection alone without adjuvant chemotherapy?
patients who are younger than two years, stage I, and <550 grams. LN's MUST be sampled and found negative for children to qualify. If LN's are not sampled, the child does not qualify for the surgery only protocol [2]
90% 4 year disease free survival

References: Ashcraft unless otherwise specified
1. Ashcraft's Pedatric Surgery. 5th edition. Chapter 67: Renal Tumors
2. COG renal biology protocol handbook. Accessed July 2011. Available at http://www.childrensoncologygroup.org/_files/disc/Surgery/RenalTumorsHandbook.pdf
3. Ehlrich et al. The value of surgery in directing therapy for patients with Wilm's tumor with pulmonary disease. A report from the National Wilm's Tumor Study Group (NWTS-5). Journal of Pediatric Surgery (2006);41:162-167

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.

A bowel prep is not necessary before colosotmy reversal in kids (APSA 2011)

In this retrospective study looking at data from three institutions, the authors compared LOS and complication rates after colostomy takedown between pediatric patients who underwent a mechanical bowel prep and those who did not.

When they reviewed the data from 272 children (187 underwent a prep) they noted a longer hospital LOS for the prep group (5.6 vs 4.4 days); 122 of them had been pre-admitted for the prep. They also noted a higher rate of wound infections for the prep group (14.4 vs 5.8%). No significant difference was noted in the rate of abdominal abscess formation, anastomotic leaks, or C-diff infections.

Despite the limitations of this retrospective study, which may be comparing individual surgeon outcomes rather than the effect of bowel preps, this is another nail in the coffin of the pre-op bowel prep dogma that will hopefully be sealed by a PRS by the same group.

Reference:
A multi-center evaluation of the role of mechanical bowel preparation in pediatric colostomy takedown.
Serrurier K, Liu j, Breckler F, et al.

What's the Pediatric Appendicitis Score (PAS) and is it actually helpful?

So who hasn't received the call for a kiddo with 'classic' appendicitis only to see the kid and send him home because he's constipated.

What if there was a consistent and reliable way of communicating the "classic'ness" of someone's abdominal pain between healthcare workers; NP from an outside hospital calling for a transfer or ED physician calling for a surgical consult.

Enter PAS.

The PAS was introduced by Maden Samuel in 2002 as a way to stratify children's risk of having appendicitis when they present with abdominal pain. The scoring system consists of 8 findings (6 worth 1 point, and 2 worth 2 points for a total score of 10 points). Since Samuel's inception, several studies have addressed the sensitivity and specificity of this scoring system and attempted to develop strategies for it's use, mostly in deciding whom to take to the OR without imaging, whom to image, and whom to send home.

Goldman et al from Sick Kids in Toronto prospectively tested the PAS on unselected children with abdominal pain. Based on the scoring system, they noted that if they had sent kids with a score less than or equal to 2 home, there would have been a 2.5% missed appendicitis rate. on the other hand, if they took anyone with a score greater or equal to 7 to the OR, the rate of negative appendectomies would have been 4%.

Another study by Bhatt et al looked at the use of PAS on children suspected of having appendicitis and noted that sending home children with a PAS of 4 or less would have resulted in a missed appendicitis rate of 2.4%, while operating on those with a PAS greater or equal to 8 would have resulted in a negative appendectomy rate of 8.8%.

Reading through the papers, it is clear that the PAS is not perfect. What about the female who is mid cycle and has severe, sudden onset abdominal pain, nausea, and right lower quadrant tenderness. I wouldn't take her to the OR without imaging even if her score was 10/10. Clearly there's an important role of the "intangible ingredient" in patient evaluation, and no scoring system could take the place of a thorough history, exam, and experience. What the PAS does do is help standardize the way we communicate the level of suspicion for appendicitis, and may have a role in developing pathways to help physicians decide on whom to image, and whom not to, before a surgical consult is called.

So instead of 'classic' appendicitis (which clearly means different things to different people), a phone call about a patient with PAS of 8 would probably be much more meaningful to all parties involved.

References:

Maden S. Pediatric appendicitis score. Journal of Pediatric Surgery 2002;37:877

Goldman et al. Prospective validation of the pediatric appendicitis score. Journal of Pediatrics 2008;153:278

Bhatt et al. Prospective validation of the pediatric appendicitis score in a Canadian pediatric emergency department. Academic Emergency Medicine 2009;16:591

What to do with a 2 YO in a C-collar?

Again, I find myself in the situation where I have to call the neurosurgery resident to evaluate a toddler in a C-collar because she keeps crying every time I touch her; making her exam unreliable. Thinking he's going to get a flex-ex, I find out that he cleared her clinically. Am I missing something?

Some basic questions to help solve this problem. First, what's the rate of C-spine injury (CSI) with or without spinal cord (SC) involvement in the setting of blunt trauma in this age group? Second,in which kids should I be worried about a CSI? Third, when are imaging studies indicated? Finally how do we clear the c-spine in a non-verbal child (whether imaging done or not)?

Polk-Williams et al reviewed the National Trauma Data Bank and identified over 95 thousand children younger than 3 years who sustained blunt trauma. The overall rate of CSI was 1.6%, with most injuries occurring in the setting of MVC's (rate of CSI doubles to 3.2%). Overall rate of SC injury (with or without a spinal column injury) was 0.4%. As expected most CSI (66%) occurred in the setting of MVC's, the second most common mechanism was falls (15%).

Ok, so CSI are uncommon, but occur more frequently with MVC (logical). But what do I do with this girl who fell off a trampoline? She has a GCS of 15, no distracting injuries, a relatively non-worrisome mechanism, but still cries every time I get close?

A multi center study of the American Association for the Surgery of Trauma looked at children younger than 3 years of age who sustained blunt trauma to clarify the approach to C-spine clearance (rate of CSI in that study was 0.66%). Based on predictors of CSI, they devised a weighted score that can be used to stratify kids based on risk for CSI and thus help determine who needs imaging and who doesn't. The score includes GCS<14 (3 points), GCSeye=1 (2 points), MVC (2 points), age 2 years or older (1 point). Based on the study, a score of 0 or 1 corresponded to a negative predictive value for CSI injury of 99.9%, and these children may be cleared without imaging studies. 70 percent of the population they studies fell into this category. Importantly, the few who escaped capture by this scoring system had other signs that prompted radiologic evaluation (splinting of neck and evidence of substantial head trauma). So based on that data, my girl in the ED, who had her eyes (and lungs) spontaneously wide open, could have been cleared without C-spine xrays. Which is fine, but I still needed to do an exam. Which is where I still am not sure that a screaming kid could have been cleared clinically. So, although based on these numbers, the chance of this girl having a CSI is minute, I'm not sure I would be comfortable clearing her C-spine without a good physical exam. References:

Polk-Williams A. et al. Cervical spine injury in young children: a National Trauma Data Bank review. Journal of Pediatric Surgery (2009). 43(9):1718-21

Pieretti-Vanmarcke R. et al. Clinical clearance of the cervical spine in blunt trauma patients younger than 3 years: A multi-center study of the American Association for the Surgery of Trauma. The Journal of Trauma (2009). 67(3):543-550

Laparoscopic repair of inguinal hernias in female children: the Inversion/ligation technique

The open repair for inguinal hernias in children is a time honored technique used by most pediatric surgeons. Different variations of laparoscopic repair techniques have been adopted by some pediatric surgeons, with the main criticism of those techniques being a high rate of recurrence (4% compared to 1% with the open repair).

Despite my overall skepticism with laparoscopic repair techniques and their outcome, one particular version used for repair of hernias in females is quite appealing.

The inversion-ligation technique for repair entails passing a laparoscopic grasper into the inguinal canal through the internal ring, grasping the distal aspect of the sac, and inverting it into the abdomen. The inverted sac is then twisted and doubly ligated with an endo-loop.

Lipskar et al looked at the outcome of 173 girls who underwent a total of 241 hernia repair operations. The mean age was 5 years. One third of patients were found to have a contralateral patent processus vaginalis/hernia. All were successfully repaired in an average time of 40 minutes and 90% were discharged home the same day. Recurrence rate was 0.8%.

The appealing part of this operation is that, unlike other laparoscopic hernia repair techniques, the hernia sac is not left within the canal, which may be a major contributor to the reported high recurrence rate in other techniques. Because of the absence of any important structures (vas etc..), the hernia sac in girls can be bluntly pulled off the round ligament and inverted.

Lipskar et al. Laparosocpic inguinal hernia inversion and ligation in female children: a review of 173 consecutive cases at a single institution. Journal of Pediatric Surgery (2010) 45,1370-1374

Which babies "sink" after PDA ligation?

30% of preemies who are over 32 weeks GA, and 60% who are under 28 weeks GA have a PDA.

Ligating a symptomatic PDA in a fragile premature infant can have substantial (but usually transient) unwanted hemodynamic consequences. The sudden ligation of the PDA causes an instantaneous rise in afterload, resulting from the obliteration of the the pop-off circuit into the low resistance pulmonary circulation, and an associated drop in preload. This sudden change may not be tolerated well by preemies, most likely due to underlying cardiac dysfunction. So how can we predict which infant is going to fare worse after ligation?

Moin et al, in a study that evaluated 100 premature infants who underwent PDA ligation, noted that 32% of preemies required vasopressor support (either starting pressors or increasing the dose of preexisting pressor support) within 72 hours of PDA ligation. Risk factors associated with need for vasopressor support were a lower gestational age (25 vs 26 weeks), lower birth weight (714 vs 870 grams), and relatively high ventilatory support (RIS>6).

Additionally, those infants who required pressor support after ligation had an increased risk of death before 36 week adjusted gestational age.

The authors cautioned that the study had several limitations by virtue of it's design and that further studies are needed to confirm their observations.

References:

Moin F et al. Risk factors predicting vasopressor use after patent ductus arteriosus ligation. American Journal of Perinatology;20(6)2003:313-320

Laparoscopic inguinal hernia repair in children. Why?

Inguinal hernia repair with high ligation of the hernia sac through an inguinal approach is one of the most commonly performed operations in the pediatric population. The laparoscopic approach to IH repair in children is certainly an attractive option, given that it entails no manipulation of cord structures, allows for the repair of recurrent hernias (initially repaired by an inguinal approach) through fresh tissue, and allows for the inspection of the contralateral internal ring (whatever implications that my have!). However, the fact that an intact hernia sac is left behind within the inguinal canal when hernias are repaired laparosocopically makes me wonder about recurrence.

Two main techniques for the closure of the internal ring from a peritoneal approach are described; the lap assisted/percutaneous closure (SEAL) and the totally laparoscopic approach. Both entail closing the internal ring (using a "purse string" or "N"-shaped type of suture) while avoiding the vas and vessels.

A recent series out of Mainz, Germany looked at over 500 patients who underwent a totally laparoscopic repair with a suture used in an "N"-shaped fashion. After a median follow up of 40 months, the recurrence rate was 4%. This dropped to 2% with the last 100 patients; an improvement that the author attributed to a refinement of the technique of internal ring closure.

Understandably, the concept of laparoscopic repair is very attractive, particularly in the setting of recurrent hernias. However, one must keep in mind that even in the most experienced hands, the recurrence rate of laparoscopic hernia repair is still 4 times higher than the classic repair.


References

Harrison et al. The subcutaneous endoscopically assisted ligation (SEAL) of the internal ring for repair of inguinal hernias in children: a novel technique. Journal of Pediatric Surgery (2005) 1177-1180

Schier F. Laparoscopic inguinal hernia repair-a prospective personal series of 542 children. Journal of Pediatric Surgery (2006) 41, 1081-84

IBD markers are not screening tools

Again, I am fascinated by how some physicians order an "IBD panel" in a kid with abdominal pain to r/o Crohn's disease (CD) or Ulcerative colitis (UC). Unless I am confused, an IBD panel's role is to help differentiate the two types of IBD, and not make the diagnosis (substantial false positives and false negatives).

Here is some information I found useful:

Main laboratory markers:

ANCA: anti-neutrophil cytoplasm antibody
ASCA: anti-Saccharomyces cervisiae antibody
Anti-OmpC: anti E coli-related outer membrane porin C
Anti I2
Anti-Cbir1: antibody against flagellin

pANCA present in two thirds of UC patients and one third of CD
pANCA-positive CD patients have a clinical picture similar to UC
ASCA (IgG or IgA) present in half of patients with CD
High titers of ASCA in the absence of pANCA highly predictive of CD
Antibodies to OmpC and I2 are associated with more strictures and internal perforations
Anti-Cibr1 associated with CD, particularly penetrating disease, fibrosing disease, and SB involvement.
pANCA positive CD patients less likely to respond to inflixamab than ASCA positive or totally seronegative

Reference:
Wyllie R, Hyams JS, Kay M (2011). Crohn's Disease. In Wyllie R, Hyams JS, Kay M (Edx.), Pediatric Gastrointestinal and Liver Disease 4th ed (pp 462-489). Elsevier.
T

This publication from the Mayo clinic is concise and useful too.

Neonatal testicular torsion: what are the options?

This read stemmed from a hallway conversation I had with my favorite French-Canadian urologist (and not because he's the only FCU I know). I had been under the impression that, unlike ovarian torsion (where you detorse the ovary and give it a chance regardless of how it looks because of the possibility of viable tissue surviving), an orchiectomy for testicular torsion with ischemia was mandatory. The rationale behind that is the theory that leaving a necrotic testicle behind results in contralateral testicular injury. This injury results from an autoimmune response that occurs because of a breach in the hematotesticular barrier on the ischemic side. Well, that turned out to be erroneous thinking.

Djahangirian et al discussed this subject in a recent outcome study from Quebec and noted that the concern for the breach of the hematotesticular barrier applies to pubertal boys only (I should have figured that one out myself, given that you need sperm to form antisperm antibodies!!). Their main discussion was regarding the different management options for neonatal testicular torsion (NTT), which is defined as torsion detected within 30 days of birth, and constitutes 5% of all cases of testicular torsion. They discussed management rationales for the affected testicle as well as the contralateral one (which is presumed to be at risk of torsion too). Regarding the management of the torsed testicle, they noted that a prenatally torsed testicle (which constituted 50% of their cases) had no chance of survival so emergent surgery in an attempt to salvage the testicle was not recommended, and the options were elective orchiectomy or observation. In cases where the torsion occurs postnatally (the other 50%), and because of a slim chance of salvage (mostly in patients who present with signs of discomfort only), emergent exploration was indicated.

As to the management of the contralateral testicle (which they noted could torse in 5% of cases, either synchronously or metachronously), they suggested that elective orchidopexy, and even observation with strict instructions to the parents regarding the signs of torsion, were viable options.

Between medico-legal concerns and guaranteed sleepless nights, observation of the contralateral testicle does not sound like a reasonable option to me, so I would stick to an exploration with orchiectomy and contralateral pexy.

Timing of surgical management of neonatal testicular torsion. Djahangirian et al. Journal of Pediatric Surgery (2010) 45, 1012-1015

Spleen/Liver injury: Grade + 1 = days of bed rest; What is the current status?

Phone conversation with R3 on call:
R3: got a kid down here, has grade 4 splenic lac. Stable
Me: so, what do you want to do?
R3: "take it out"

To be fair, the kid did "collapse" on the way to the bathroom, but probably form a vagal response.

Obviously, very few Pediatric Surgeons would argue that non-operative management is the general strategy in a stable child with blunt liver or splenic trauma. What constitutes non-operative management, on the other hand, is slightly more controversial.

Until recently, we had been treating kids with liver and splenic injury with bed rest, where the days in bed were determined by the grade of the injury. Grade + 1 = days in bed (grade + 2 = weeks of limited activity). In this protocol, as pointed out by St Peter et al. in a paper published in this month's JPS, days of bed rest are considered treatment variables, suggesting that a Grade 3 splenic lac needs 4 days to stabilize. Recent literature on the subject of non-operative management of liver and splenic injury has shifted focus from an absolute grade-defined management algorithm to one determined by hemodynamic stability and physical findings in an attempt to safely truncate what some would concider to be an overkill in terms of hospital stay.

St Peter et al prospectively studies 131 patients with liver and splenic injury from blunt trauma and noted that a protocol for monitoring (not therapy), where stable patients with grades I or II splenic injury are monitored for one night (defined as spending a night in their room regardless of time admission), while those who had a grade III or more, spend two nights in the hospital, is a safe alternative that could shorten hospital stay. Based on their protocol, if a patient needed a transfusion, the clock on observation was re-zero'd.

Using this protocol, the splenic salvage rate was 98.7%, regardless of associated injuries and transfusion requirements (13% required blood transfusion for their splenic and liver injuries). Obviously, and based on this protocol, there was a substantial decrease in hospital stay requirements.

St Peter et al. Prospective validation of an abbreviated bedrest protocol in the management of blunt spleen and liver injury in children. Journal of Pediatric Surgery (2011) 46, 173-177

What is the significance of CT-only lung lesions in Wilms' Tumor

The advent of CT imaging of the chest as part of the work up of Wilm's tumor has created substantial controversy. It is natural to assume that lesions of the lung found on CT scan,in the setting of a known primary tumor, represent metastatic disease. False. A study by Ehrlich et al, from the National Wilms' Tumor Study 5 showed that up to a third of lung lesions found on CT only (negative CXR) were not malignant (by pathology). This raises the question of how CT-only lesions should change the management.

Based on COG recommendations, patients who are local stage I or II FH Wilms' tumor should undergo biopsy of CT-only lung lesions to gauge therapy. Patients with Stage III or IV disease, who are enrolled in AREN0533 trial (evaluating response of lung lesions to 3 drug therapy after 6 weeks) are not treated differently in the presence of lung lesions unless these lesions persist after 6 weeks, at which time they would be treated with additional lung radiation, preferably after confirming their malignant nature with biopsy.

Erlich PF. The value of surgery in directing therapy for patients with Wilms’ tumor with pulmonary disease. J Ped Surg (2006) 41, 162-167

"We may need to recannulate this CDH baby!"

That's probably the last thing one wants to hear after answering a page!

Fortunately, the kiddo is doing better and did not require a second ECMO run (near diaphragmatic agenesis). This prompted a search for some literature on the subject of second run ECMO. Took a bit of research but found an article by Meehan et al. that looked at 205 patients from the ELSO neonatal registry who underwent multiple ECMO runs.

My main concern whenever the subject of potential need for recannulation comes up is the issue of recannulating the right CCA and CJV (A scenario encountered in 56% of patients in this study), with the potential for embolic events.

In their review, the authors noted a 20% increase in complication rates, with the largest increase in complication rates being for neurologic (134% increase) and infectious complications (79% increase). The most common type of neurologic complications were clinical seizures and radiologically documented cerebral strokes.

Overall survival after a second run was 38% (32% for CDH).

Journal of Pediatric Surgery, Vol 37, No 6 (June), 2002:pp 845-850