Definitions of Laboratory and Clinical Tumor Lysis Syndrome

The tumor lysis syndrome is the most common disease-related emergency encountered by physicians caring for children or adults with hematologic cancers. This syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte and metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure.
In the current classification system of Cairo and Bishop, the tumor lysis syndrome can be classified as laboratory or clinical.
Definitions of Laboratory and Clinical Tumor Lysis Syndrome.*

Metabolic Abnormality	Criteria for Classification of Laboratory Tumor Lysis Syndrome	Criteria for Classification of Clinical Tumor Lysis Syndrome
Hyperuricemia	Uric acid >8.0 mg/dl (475.8 umol/liter) in adults or above the upper limit of the normal range for age in children
Hyperphosphatemia	Phosphorus >4.5 mg/dl (1.5 mmol/liter) in adults or >6.5 mg/dl (2.1 mmol/liter) in children
Hyperkalemia	Potassium >6.0 mmol/liter	Cardiac dysrhythmia or sudden death probably or definitely caused by hyperkalemia
Hypocalcemia	Corrected calcium <7.0 mg/dl (1.75 mmol/liter) or ionized calcium <1.12 (0.3 mmol/liter)†	Cardiac dysrhythmia, sudden death, seizure, neuromuscular irritability (tetany, paresthesias, muscle twitching, carpopedal spasm, Trousseau’s sign, Chvostek’s sign, laryngospasm, or bronchospasm), hypotension, or heart failure probably or definitely caused by hypocalcemia
Acute kidney injury‡	Not applicable	Increase in the serum creatinine level of 0.3 mg/dl (26.5 umol/liter) (or a single value >1.5 times the upper limit of the age-appropriate normal range if no baseline creatinine measurement is available) or the presence of oliguria, defined as an average urine output of <0.5 ml/kg/hr for 6 hr

* In laboratory tumor lysis syndrome, two or more metabolic abnormalities must be present during the same 24-hour period within 3 days before the start of therapy or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.
† The corrected calcium level in milligrams per deciliter = measured calcium level in milligrams per deciliter + 0.8 × (4 - albumin in grams per deciliter).
‡ Acute kidney injury is defined as an increase in the creatinine level of at least 0.3 mg per deciliter (26.5 umol per liter) or a period of oliguria lasting 6 hours or more. By definition, if acute kidney injury is present, the patient has clinical tumor lysis syndrome.

References:

1. Howard SC, Jones DP, Pui C-H. The Tumor Lysis Syndrome. N Engl J Med 2011; 364:1844-1854 [Medline]
2. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. 2008 Jun 1;26(16):2767-78. [Medline]

Criteria for Chronic Respiratory Failure in Infants and Children

Criteria for Chronic Respiratory Failure due to Cardiopulmonary Disorders in Infants and Children

Clinical criteria

• Decreased inspiratory breath sounds
• Increased retractions, use of accessory muscles
• Cyanosis breathing room air
• Decreased level of normal activity/function
• Poor weight gain (mass) (IMPORTANT)

Physiological criteria

• PaCO₂ > 45 mm Hg
• PaO₂ < 65 mm Hg
• Oxygen saturation < 95% breathing room air

Criteria for Chronic Respiratory Insufficiency Due to Central Nervous System, Neuromuscular, and Skeletal Conditions in Infants and Children

Clinical criteria

• Weak cough
• Retained airway secretions
• Increased use of accessory muscles
• Incompetent swallowing
• Weak or absent gag reflex
• Decreased level of normal activity/function (IMPORTANT)

Physiological criteria

• Vital capacity < 15 mL/kg
• Inspiratory force < 20 cm H₂0
• PaCO₂ > 40 mm Hg
• PaO₂ < 70 mm Hg
• Oxygen saturation < 97% breathing room air

References:

1. Nørregaard O. Noninvasive ventilation in children. Eur Respir J. 2002 Nov;20(5):1332-42. [Medline]

Diagnostic Criteria for Refractory Ascites

For the correct diagnosis of true refractory ascites, the patient’s condition should fulfill the following criteria.

Diuretic-resistant ascites
Failure of mobilization or the early recurrence of ascites which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment is called diuretic-resistant ascites.

Diuretic-intractable ascites
Failure of mobilization or the early recurrence of ascites which cannot be prevented because of the development of diuretic-induced complications that prevent the use of an effective diuretic dosage is called diuretic-intractable ascites.

Treatment duration
Patients must be on intensive diuretic therapy (spironolactone 400 mg/d and furosemide 160 mg/d) for at least 1 wk and on a salt-restricted diet of less than 90 mmol/d.

Lack of response
Mean weight loss of less than 0.8 kg over 4 d and urinary sodium output less than the sodium intake.

Early ascites recurrence
There is an reappearance of grade 2 or 3 ascites (clinically detectable) within 4 wk of initial mobilization. However, it is important to notice that in patients with severe peripheral edema, reaccumulation of ascites within 2-3 d of paracentesis must not be considered as early ascites recurrence because it represents a shift of interstitial fluid to the intraperitoneal space.

Diuretic-induced complications
Diuretic-induced hepatic encephalopathy is the development of encephalopathy in the absence of any other precipitating factor. Diuretic-induced renal impairment is indicated by an increase of serum creatinine by > 100% to a value of > 2 mg/dL in patients with ascites otherwise responding to treatment.
Diuretic-induced hyponatremia is defined as a decrease of serum sodium by > 10 mEq/L to a serum sodium of < 125 mEq/L. Diuretic-induced hypo- or hyperkalemia is defined as a change in serum potassium to < 3 mEq/L or > 6 mEq/L despite appropriate measures.
In addition to this, we should exclude dietary non-compliance (patient taking excess sodium in diet) and exclude the use of nonsteroidal antiinflammatory drugs (NSAIDs), which can induce renal vasoconstriction and diminish diuretic responsiveness

References:

1. Hou W, Sanyal AJ. Ascites: diagnosis and management. Med Clin North Am. 2009 Jul;93(4):801-17. [Medline]
2. Senousy BE, Draganov PV. Evaluation and management of patients with refractory ascites. World J Gastroenterol. 2009 Jan 7;15(1):67-80. [Medline]
3. Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, Jimenez W, Planas R, Arroyo V. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology. 2003 Jul;38(1):258-66. [Medline]

Revised Criteria for Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome)

Amsterdam Criteria (1991)

Three or more relatives with colorectal cancer, plus all of the following:

• One affected patient should be a first-degree relative of the other two;
• Colorectal cancer should involve at least two generations;
• At least one case of colorectal cancer should have been diagnosed before the age of 50 years.

Amsterdam II Criteria (Revised International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Criteria 1998)

Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter or renal pelvis) plus all of the following:

• One affected patient should be a first-degree relative of the other two;
• Two or more successive generations should be affected;
• Cancer in one or more affected relatives should be diagnosed before the age of 50 years;
• Familial adenomatous polyposis should be excluded in any cases of colorectal cancer;
• Tumours should be verified by pathological examination.

Modified Amsterdam Criteria

Just one of these criteria need to be met:

• Very small families, which can not be further expanded, can be considered to have HNPCC with only two colorectal cancers in first-degree relatives if at least two generations have the cancer and at least one case of colorectal cancer was diagnosed by the age of 55 years;
• In families with two first-degree relatives affected by colorectal cancer, the presence of a third relative with an unusual early-onset neoplasm or endometrial cancer is sufficient.

Revised Bethesda Criteria (2003)

Just one these criteria need to be met:

• Diagnosed with colorectal cancer before the age of 50 years;
• Synchronous or metachronous colorectal or other HNPCC-related tumours (which include stomach, bladder, ureter, renal pelvis, biliary tract, brain (glioblastoma), sebaceous gland adenomas, keratoacanthomas and carcinoma of the small bowel), regardless of age;
• Colorectal cancer with a high-microsatellite instability morphology that was diagnosed before the age of 60 years;
• Colorectal cancer with one or more first-degree relatives with colorectal cancer or other HNPCC-related tumours. One of the cancers must have been diagnosed before the age of 50 years (this includes adenoma, which must have been diagnosed before the age of 40 years);
• Colorectal cancer with two or more relatives with colorectal cancer or other HNPCC-related tumours, regardless of age.

References:

1. Chung DC, Rustgi AK. The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med. 2003 Apr 1;138(7):560-70. [Medline]
2. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005 May 5;352(18):1851-60. [Medline]
3. Pinol V, Castells A, Andreu M, Castellvi-Bel S, Alenda C, Llor X, Xicola RM, Rodriguez-Moranta F, Paya A, Jover R, Bessa X; Gastrointestinal Oncology Group of the Spanish Gastroenterological Association. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005 Apr 27;293(16):1986-94. [Medline]

Classification for Chagas Cardiomyopathy

Chagas' disease is caused by a protozoan parasite, Trypanosoma cruzi, that is transmitted to humans through the feces of infected bloodsucking insects in endemic areas of Latin America, or occasionally by nonvectorial mechanisms, such as blood transfusion. Cardiac involvement, which typically appears decades after the initial infection, may result in cardiac arrhythmias, ventricular aneurysm, congestive heart failure, thromboembolism, and sudden cardiac death.

Chagas cardiomyopathy: classification according to American College of Cardiology/American Heart Association
A: Normal ECG findings, normal heart size, normal left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class I
B: Abnormal ECG findings, normal heart size, normal LVEF, NYHA class I
C: Abnormal ECG findings, increased heart size, decreased LVEF, NYHA class II-III
D: Abnormal ECG findings, increased heart size, decreased LVEF, NYHA class IV

Chagas cardiomyopathy: Brazilian consensus classification
A: Abnormal ECG findings, normal echocardiogram findings, no signs of CHF
B1: Abnormal ECG findings, abnormal echocardiogram findings with LVEF >45%, no signs of CHF
B2: Abnormal ECG findings, abnormal echocardiogram findings with LVEF <45%, no signs of CHF
C: Abnormal ECG findings, abnormal echocardiogram findings, compensated CHF
D: Abnormal ECG findings, abnormal echocardiogram findings, refractory CHF

Chagas cardiomyopathy: modified Los Andes classification
IA: Normal ECG findings, normal echocardiogram findings, no signs of CHF
IB: Normal ECG findings, abnormal echocardiogram findings, no signs of CHF
II: Abnormal ECG findings, abnormal echocardiogram findings, no signs of CHF
III: Abnormal ECG findings, abnormal echocardiogram findings, CHF

Chagas cardiomyopathy: modified Kuschnir classification
0: Normal ECG findings and normal heart size (usually based on chest radiography)
I: Abnormal ECG findings and normal heart size (usually based on chest radiography)
II: Left ventricular enlargement
III: Congestive heart failure


References

1. Acquatella H. Echocardiography in Chagas heart disease. Circulation. 2007 Mar 6;115(9):1124-31. [Medline]
2. Andrade JP, Marin Neto JA, Paola AA, Vilas-Boas F, Oliveira GM, Bacal F, Bocchi EA, Almeida DR, Fragata Filho AA, Moreira Mda C, Xavier SS, Oliveira Junior WA, Dias JC. I Latin American Guidelines for the diagnosis and treatment of chagas' heart disease: executive summary. Arq Bras Cardiol. 2011 Jun;96(6):434-42. [Medline]
3. Carrasco HA, Barboza JS, Inglessis G, Fuenmayor A, Molina C. Left ventricular cineangiography in Chagas' disease: detection of early myocardial damage. Am Heart J. 1982 Sep;104(3):595-602 [Medline]
4. Kuschnir E, Sgammini H, Castro R, Evequoz C, Ledesma R, Brunetto J. Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy. Arq Bras Cardiol. 1985 Oct;45(4):249-56. [Medline]