Neo-adjuvant chemotherapy for hepatoblastoma: Do tumors shrink away from major vascular structures?

No.

This was an eye-opening study by Murphy et al who looked at patterns of response of hepatoblastoma (both volume reduction and regression away from major vascular structures)  treated with neo-adjuvant chemotherapy.

It was eye opening for two reasons.

The first reason is that one would assume that substantial shrinkage of tumor would translate into substantial regression away from major vascular structures (and subsequently facilitate resection).  It turns out that although these tumors respond well to neo-adjuvant chemotherapy, they shrink towards major vascular structures (as if anchored to their main blood supply), and not centripetally.  In fact, the authors noted that the tumors, at most, regressed an average of 1 mm from major vascular structures.

The second, and more important eye opener, was the remark made by Dr Meyers in the discussion section of the paper.  The authors were addressing the recommendation by the COG protocol (AHEP0731) that patient with margins less than 1 cm from major vascular structures not undergo attempts at primary resection but receive neo-adjuvant chemotherapy.  The authors conculded that chemotherapy brought only a few patients closer to respectability  (because it brought only a few patients to this 1 cm level)

The misinterpretation of COG recommendations lies in the following:  The 1 cm recommended margin away from major vascular structures is intended to encourage neoadjuvant chemotherapy and avoid positive margins with attempts at primary resection.  So really, the < 1 cm margin is more an indication for neo-adjuvant chemotherapy than a contraindication for surgery.

Subsequently, once a patient has received neo-adjuvant chemotherapy, the entire < 1 cm business is out the window, and resection should be attempted if deemed possible and safe regardless of radiologic vascular margins.

Outcome of endorectal pull through with ileal-pouch vs straight ileo-anal anastomosis

The satisfaction gained from taking a child from a state of misery and malnutrition to "he is doing so wonderfully after his colon came out" is only tempered by the conversation that must follow. Asking a child and their parents to choose between too evils (multiple bowel movements/incontinence vs the risk of pouch complications/pouchitis) when discussing the next step can only be made more palatable when we have some outcome data to share.

A paper by Seetharamaiah et al in published in JPS in 2009 provided that data.

The authors retrospectively looked at 203 children (average age 15 years) who underwent either a straight ileo anal pull through vs a pouch anastomosis for UC or familial polyposis.  The authors compared several outcome variables, including the rate of complications (pouchitis/enteritis) and long term bowel functions as reflected by the modified Hoschneider scoring system (incorporates number/consistency of stool, risk of daytime/nighttime incontinence, severity of urgency, and need for therapy for stool control).

The authors noted that, as one would expect, the patients who underwent a straight pull through had more BM's per day than those who underwent a pouch anastomosis.  Interestingly, after 24 months, the number of bowel movements approached that of patients who underwent a pouch anastomosis (mean number of bowel movements for straight pull through vs. pouch anastomosis were 8 vs 6 per day, respectively).

As to the general quality of bowel function, both groups eventually scored similarly on the modified Holschneider coring system, and ultimately ~90% became totally continent after 24 months, regardless of type of operation.

As to pouchitis, the nagging complication of pouch creation, the authors noted that patients had a 49% risk of documented pouchitis, vs 24% risk of ileitis, the counterpart in a patient with a straight pull through.

Based on this data, it appears that both options area reasonable, with the benefit of a better outcome in terms of bowel function for the first two years, when a pouch is created, balanced against the increased risk of pouchitis and what is entails in terms of pain/discomfort, need for antibiotics, and potentially hospital admissions. 

Which kids with Wilm's tumor qualify for no post op adjuvant chemotherapy?

Adjuvant chemotherapy for favorable histology Wilm's tumor consists of either regimen EE-4A (vincristine and dactinomycin) or DD-4A (vincristine, dactinomycin, and doxorubicin) based on staging and the status of loss of heterozygosity (1p and 17q).

One special subset of patients with Wilm's tumor has been found to have a good outcome without chemotherapy.  Specifically, patients younger than 2 years of age, with stage I FH Wilm's tumor that weighs less than 550 g have an estimated 5-year EFS of 84% (compared to 97% for those receiving EE-4A).  Of the patients who receive no adjuvant therapy and relapse, the salvage rate (using DD-4A) exceeds that of those who are treated with EE-4A and relapse.

This protocol underlines importance of lymph node sampling (irrespective of gross appearance) as part of the surgical management of Wilm's tumor.  In this case, if nodes are not sampled, the patient would not qualify for the no-chemotherapy option.

Reference:
Coran, A.G (2012) Pediatric Surgery. Philadelphia, PA. Elsevier

Hypophosphatemia after major liver resection

A conversation about hypophosphatemia after a recent liver resection elicited a literature search on the subject.  A paucity of material in the pediatric surgical literature (a quick search yielded only one case report) prompted a move to the adult literature (yes, I know, they are not just small adults!).

A retrospective study by Salem et al looked at post operative phosphate levels in 20 patients who underwent major liver resection.  The authors confirmed the known association between hypophosphatemia and major liver resection with a drop in phosphate levels of an average of 1.1 mg/dl and a nadir at post operative day 2.

They discussed several potential explanations, including the common assumption that the drop in phosphate levels is due to the consumption of phosphate ions by the aggressively regenerating liver, but noted that these patients also experience hyperphosphaturea.  This finding contradicted what would be expected in the setting of phosphate ion depletion by the liver.

Their alternate explanation involved some form of messenger molecule controlled by the liver, and depleted with a major liver resection.  They described this as a disruption in normal hepatorenal messaging that results in phosphate ion wasting by the kidney.  This starts immediately postoperatively, peaks at 2 days post operatively, and usually resolves by post op day 5.

Thoracostomy and fibrinolysis for the management of empyema

A little throw back to 2009 prompted by a discussion on management of parapneumonic effusion/empyema.

In the frequently quoted study out of The Center for Prospective Clinical Trials in Kansas City, the authors compared the effectiveness of VATS vs thoracostomy/fibrinolysis in 36 patients.  Empyema was defined based on imaging characteristics or WBC content and then managed with either VATS or thoracostomy (chest catheter drainage with a12 F tube) with fibrinolysis using 3 doses of 4 mg of Altase given over a 48 hour period.

No significant difference was found in the outcomes assessed, which were days of hospitalization (6.9 vs. 6.8 days), days of oxygen requirement (2.3 days), days until afebrile (3.1 vs. 3.8), or analgesic requirements. The difference in cost was $11.7K vs $7.6K between VATS and thoracostomy /fibrinolysis, respectively.

Although fibrinolysis was sufficient for most patients, 16.6% still needed VATS; an important point to mention to parents when discussing the procedure.

Another important point to stress here is that in many institutions, the most common chest catheters available are 8.5 Fr (and not 12 Fr), and one should make sure the appropriate catheter is used to optimize the chance for success.

Encephalitis associated with ovarian tumors

It is one thing to learn something new every day, but another to come across something you have never heard of.

Enter anti-NMDAR encephalitis secondary to ovarian teratomas.

Anti-NMDAR encephalitis syndrome is a constellation of psychiatric symptoms, memory changes, altered level of consciousness, and/or central hypoventilation due to the interaction of antibodies to NMDAR (receptor in brain tissue) with the hippocampus.

This condition can present at any age group, and can be associated with teratomas (in 50% of females above 12 years of age with anti NMDAR encephalitis); mainly the ovarian type.  It is the second most common type of autoimmune encephalitis, and is believed to be the result of interaction of auto antibodies to NMDAR (generated in response to ectopic neuronal tissue in the teratoma) with the hippocampus.  The diagnosis is confirmed with anti-NMDAR antibodies in the blood or CSF.

The treatment for this condition consists of immune therapy (steroids/plasmapharesis/IV immunoglobulin), tumor resection, and possible need for immune suppression.

80% of patient have substantial improvement of symptoms within 24 months of initiation of therapy.  During this time, the risk of relapse is 12%.

News to me.

Reference:

Tiltulaer et al.  Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis Lancet Neurol (2013) 12:2-157

How effective is bracing in the management of pectus carinatum?

A recent conversation on bracing for pectus carinatum prompted a review of what’s new in the literature.

The principle of bracing relies on the application of constant (23 hours a day) external pressure to a carinatum deformity using a specially made padded brace.  The brace pressure is adjusted to the maximum tolerated by the patient and then left in place until the deformity resolves (corrective phase).  At that point, the patient goes into the maintenance phase, where he/she wears the brace for 8 hours a day until the end of the growth spurt.

In the current issue of JPS, Lee et al. looked at the outcome of bracing for pectus carinatum in terms of average time for the corrective and maintenance phases, compliance, and final outcome.  They noted that, overall, the corrective phase lasted 7±7.3 months. The corrective phase was shorter (4.2±0.9 months) in kids who had not reached Tanner stage IV of maturity when compared to those who had (8.0±7.1 months); a statistically significant difference.

Interestingly, 45% of their patients were considered treatment failures, mainly because of loss to follow up (29%) or non-compliance (15%).

The authors commented on the issue of compliance, suggesting that the fact that results can be noted in as little as a month after brace application encourages patients to accept increasing pressures and improves compliance. However, more work is needed in researching causes of poor compliance and ways to improve it.

Reference:

Lee RT et al. Bracing is an effective therapy for pectus excavatum: interim results. JPS (2013) 48(1):184-90