Monday, November 28, 2011

MRI - Fast t2 sequences explained

Imaging of the urinary tract: the role of CT and MRI

Melanie P. Hiornscorresponding author
Great Ormond Street Hospital for Children - Radiology Department, Great Ormond Street, London, WC1N 3JH UK
Melanie P. Hiorns, Email: hiornm XatX corresponding author
Received March 9, 2010; Revised August 4, 2010; Accepted August 4, 2010.

Computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly valuable tools for assessing the urinary tract in adults and children. However, their imaging capabilities, while overlapping in some respects, should be considered as complementary, as each technique offers specific advantages and disadvantages both in actual inherent qualities of the technique and in specific patients and with a specific diagnostic question. The use of CT and MRI should therefore be tailored to the patient and the clinical question. For the scope of this article, the advantages and disadvantages of these techniques in children will be considered; different considerations will apply in adult practice.
Keywords: Magnetic resonance imaging, Computed tomography, Ultrasonography, Child, Kidney, Urinary tract, Diagnostic imaging

Computed tomography (CT) was invented by Sir Godfrey Hounsfield and was introduced into medical practice in 1973 [1–3]. The technique relies on the original theory that one can determine what is inside a box by taking X-ray "readings" at all angles around the object (tomograms). A computer then takes input from the X-rays at various angles to create an image of the object in slices, hence the name computed tomography. CT is therefore an X-ray technique and uses ionizing radiation. X-rays (whether conventional, plain radiographs or CT) give pictorial information on the density of an object or material. A CT image is therefore a pictorial demonstration of all the densities in the object, with high-density material (bone, calcium, metalwork) being represented as white and low-density materials being dark grey or black (air, fat). Their density can be measured in Hounsfield units (HU), and this can give the radiologist important information about the type of material (or tissue). Water is used as the reference point and has a value of between –7 and +7 HU (typically 0 HU), bone and other calcification will be of higher density (?500 HU), fat will be of lower density (–25 to –250 HU), and soft tissues are in the range +10 to +60 HU.
Modern CT scanners are very fast and can scan the abdomen and pelvis in typically 5–7 s once the planning view (the 'scout' or 'scanogram') has been set up. This has great advantages in children, as for the most part, children will not need to have a general anesthetic to ensure they keep still. Babies can undergo "feed and wrap" and will generally sleep through the scan; toddlers and preschool children can be scanned with encouragement and caregiver support (or occasionally with mild sedation), and older children are easily able to tolerate the short scan times. Modern scanners typically have a slice thickness of <1 mm (0.6–0.75 mm) depending on the manufacturer. This allows for very detailed information that can be reconstructed in other planes, such as sagittal and coronal projections, which are often very helpful to the physician in understanding the image. Three dimensional (3D) images can also be produced in postprocessing, allowing rotating visualization of any part of the image that is required. CT provides a high spatial resolution image (the ability to distinguish two structures an arbitrarily small distance from each other as separate) with low noise, giving exquisite anatomical depiction, but it cannot give as much information with respect to processes within different tissues types, such as inflammation or necrosis, unless these are quite pronounced. The use of intravenously administered contrast medium helps in this respect and would be given routinely unless the main clinical question was regarding calcification or high-density objects (such as when looking for renal calculi). There is almost no indication in children for doing both pre- and postcontrast scans as part of the same examination. The only occasion for routinely performing a precontrast (unenhanced) scan is when evaluating calculi, and if the examination is solely for that purpose, then there is no indication to routinely perform a postcontrast scan as well. Conversely, if there is no diagnostic concern regarding calculi, then only a postcontrast scan should be performed, as there is so little additional diagnostic yield (if any) from doing both a pre- and postcontrast scan, and the significant radiation dose from the additional precontrast scan cannot be justified. All patients should be asked for any history of contrast allergy (or other severe allergies) before contrast is given intravenously (IV). Contrast is always most safely administered in the setting of good effective volume and hydration. Moreover, in the setting of a depressed glomerular filtration rate (GFR), consideration should be given to both hydration and alkalinization and, in some instances, there may be a role for the use of postcontrast dialysis. Planning for imaging children with depressed GFR is best accomplished in a multidisciplinary fashion, with input from both radiologist and nephrologist. Intravenously administered contrast must not be given in severe renal failure unless the patient will subsequently be dialyzed. In mild renal failure, a risk assessment (based on the potential benefit of the examination) must be performed by the clinician, and the patient must be well hydrated beforehand. CT is a high-radiation-dose technique and as such is used much more cautiously and infrequently in children than in adults, with children being many times more biosensitive to radiation than adults. Background radiation is typically 2–3 mSv per year, and a CT scan of the abdomen and pelvis is approximately 2–6 mSv, or the equivalent of 200–300 chest X-rays. Much effort is being made by pediatric radiologists to reduce radiation doses in children, especially in CT imaging, and information regarding this can be found at Consideration should be given to performing specialized imaging studies that are elective in nature in facilities with pediatric expertise and pediatric imaging protocols, if these are available.
Magnetic resonance imaging (MRI) provides much greater contrast between different soft tissues [4] than does CT, as it relies on obtaining a radiofrequency (RF) signal from alignment and subsequent relaxation of protons in hydrogen atoms in water in the body. Soft tissue throughout the body will have varying water contents depending on cell types and the processes going on in and around those cells (e.g. normal different tissues, inflammation, tumor, infection, etc). An MR scanner uses a powerful magnetic field to align the nuclear magnetization of protons of hydrogen atoms in water (intra- and extracellular), and RF fields are then applied to alter the alignment of this magnetization, causing hydrogen nuclei to produce a rotating magnetic field that is detectable by the scanner. When RF fields are reversed, the protons relax to their normal state and give off a tiny RF signal that is detected by the scanner and is used to construct the image. Different tissues return to their equilibrium state at different rates. By changing the parameters of the scan, this effect is used to create an image that depicts the different tissues by showing the contrast between them. In a typical MRI scan, several different pulse sequences are performed to best exploit the different signals between tissues and give the most information. The main advantage of MRI over CT is that it gives far better contrast resolution (the ability to distinguish the differences between two arbitrarily similar but not identical tissues) and thus its ability to demonstrate changes between normal and pathological tissues. A sequence may last between a few seconds to several minutes, with most routine sequences lasting 1–3 min. Between five and ten sequences would usually be performed. MRI can produce images in any plane desired, and this is achieved by the radiographer or technician when setting up scan parameters. Sequences can be selected specifically to demonstrate particular qualities of tissues, such as water content. For example, with particular values of the echo time (TE) and the repetition time (TR), which are basic parameters of image acquisition, a sequence may take on the property of T2 weighting. On a T2-weighted scan, water- and fluid-containing tissues are bright (most modern T2 sequences are actually fast T2 sequences), and fat-containing tissues are dark. The reverse is true for T1-weighted images. Damaged tissue tends to develop edema, which makes a T2-weighted sequence sensitive for pathology and generally able to distinguish pathologic tissue from normal tissue. Heavily T2-weighted sequences are especially useful in the urinary tract, as water-containing structures are bright white, such as the collecting system and the bladder.
MRI contrast agents are frequently used. Most common of these is gadolinium, which is given intravenously. These agents work by shortening the T1 or T2 relaxation time of protons nearby. Reduction of T1 relaxation time results in a hypersignal with a reduced T2 relaxation time, thus reducing both T2 and T2* signals. Gadolinium is therefore of most benefit in T1-based sequences. A rare but severe complication of gadolinium use is nephrogenic systemic fibrosis (NSF), which causes fibrosis in various tissues and organs. Patients with poor renal function are considered a greater risk of NSF, and therefore, gadolinium contrast agents must only be used with caution in these patients. As a result, gadolinium-containing contrast is now considered contraindicated in patients with an estimated GFR <60 ml/min and especially <30 ml/min [5]. Depressed GFR encompasses both acute and chronic kidney injury. As such, individuals with transient renal dysfunction should also be considered at risk, even though their usual GFR may be normal.
MRI scans will usually take 30–45 min and therefore generally require a general anesthetic in children from approximately 1–6 or 7 years of age. Older children are usually able to cooperate, but if they are unable to remain still and limit any movement for this length of time, they may also require a general anesthetic. Younger children (<12 months) may undergo feed and wrap or sedation. Further details of the practical aspects are covered in the pediatric MRI literature [6–8] (Table  1).

Table 1

Comparison of advantages and disadvantages between computed tomography (CT) and magnetic resonance (MR) imaging modalities

Uses ionizing radiation, high-dose procedureUses magnetic resonance, no ionizing radiation
Excellent spatial resolutionExcellent contrast resolution
Actual scanning time measured in seconds (typically <10 s) Actual scanning time measured in minutes (typically 45 min)
Rarely requires general anesthetic in childrenFrequently requires general anesthetic in children, depending on age
Excellent at showing calcificationPoor at showing calcification (signal void)
Poor at showing edema or pathological changes in specific tissue types Excellent at showing edema and pathological changes in specific tissue types
Usually requires intravenous contrast (unless looking for calcification when not required) Usually requires intravenous administration of contrast (but certain sequences can be tailored if this is contraindicated)
No known risk of nephrogenic systemic fibrosis (NSF) Risk of NSF (rare, but renal patients believed to be at increased risk)
Widely availableLess widely available, especially for children
Less expensiveExpensive
Usually available as an emergency imaging techniqueNot routinely available as an emergency technique
No significant contraindicationsContraindicated in patients with any internal ferrous objects (pacemakers, defibrillators, recent orthopedic metalware, other implanted metallic devices, metallic foreign bodies)
Open-style scannersGenerally quite enclosed scanners – risk of claustrophobia
Can only scan in one plane (but can do reconstructed images later)Can scan in any plane
Few artefactsProne to artefacts depending on sequence type (especially motion artifact)

Imaging the urinary tract – which modality to use for first-line examination?

In imaging the urinary tract in children, the modality of choice for the initial examination will almost universally be ultrasound (US). US is inexpensive, immediate, painless, requires no sedation or anesthetic, is widely available, and is radiation free. In children, the urinary tract is easily visualized, as usually children have less body fat than adults, and the kidneys and bladder are relatively superficial structures. Children should be scanned both supine and prone, and the posterior approach (with the child lying prone) often gives the best anatomical detail of the kidneys. US can be used to scan in any plane at the discretion of the operator, and whereas the technique is entirely operator dependent, most centers have staff with a high level of skill. In most pediatric centers, it is considered completely unacceptable to proceed to CT or MRI in routine practice unless US had already been performed and had been unable to fully answer the diagnostic question. Acute multiorgan trauma would be the main exception to this. It is common practice in adult medicine to perform a CT scan of the abdomen and pelvis as the first-line examination for renal colic. In children, the first-line examination, even in renal colic, should ideally be US (on radiation dose risk vs. benefit considerations), recognizing that a few children will still need to proceed to CT. However, there is some variation in this practice between North America and Europe and on the availability of US expertise out of hours. Renal colic in children is much less common than in adults, even in children with known stone disease, and their stones pass more readily. US can show renal calculi with exquisite detail, demonstrating stones down to approximately 1–2 mm in diameter, and is also highly sensitive in the bladder. It is less sensitive, however, in the ureters, which may be obscured by bowel and other pelvic structures, so in the context of a normal US and ongoing clinical features suggestive of calculi (colicky pain, hematuria, known existing stone disease), CT may still be indicated. There is further discussion of this topic in the section "Calcification in the urinary tract". US is the first-choice examination for all other pathologies relating to the kidney and urinary tract.

The use of CT and MR for specific clinical indications
Congenital conditions
In pediatric practice, many congenital conditions of the urinary tract are demonstrated in utero on antenatal scans, whereas some are only detected in infancy or later due to subsequent complications. Ninety percent of fetal kidneys can be identified by 17–20 weeks of gestation and 95% by 22 weeks. Both antenatally and postnatally, US remains the examination of choice in demonstrating kidney and urinary tract anatomy. Structural urinary tract anomalies include renal dysplasia, renal hypoplasia, renal aplasia, multicystic dysplastic kidney, pelviureteric junction obstruction, duplication anomalies, fusion anomalies, renal ectopia, ureteroceles, cystic kidney diseases, and posterior urethral valves. All of these may be demonstrated by US, with additional information being acquired in some cases by other modalities (such as nuclear medicine imaging or fluoroscopy). MRI may subsequently be useful in these patients, as illustrated in Fig. 1 for cystic disease, either in the further workup following US [7, 9] when the clinical question has not been resolved, or when the child presents with (or has) complications that remain unexplained by US or require further delineation [10–12]. Heavily T2-weighted sequences (water-based sequences) are very useful in demonstrating dilatation of the urinary tract secondary to congenital anomalies, such as duplex kidneys with dilated moieties and occult moieties in a previously undiagnosed duplex kidney [13] (Fig. 2), and for demonstrating the exact anatomy of fusion anomalies, such as a crossed, fused, ectopic kidney and horseshoe kidney [4, 6].

Fig. 1
Magnetic resonance image: coronal T2 sequence in a 6-month-old girl with autosomal dominant polycystic kidney disease showing multiples high-signal cysts throughout both kidneys

Fig. 2
Magnetic resonance imaging: an unexpected right-sided duplex kidney in a 7-month-old girl whose anatomy could not be delineated by ultrasound, with a tiny lower moiety that is almost hidden by the dilated upper moiety (arrow)

CT arteriography (CTA) is sometimes performed in instances of known horseshoe kidney when surgery is being planned. This is to optimally delineate the multiple vessels that often supply these kidneys before surgery is undertaken. Pelviureteric junction obstruction can usually be diagnosed adequately on US, but a crossing vessel may be demonstrated by MRI (Fig. 3) [14], which cannot be visualized by US; in very gross hydronephrosis, MRI may give a better demonstration of the anatomy (Fig. 4).

Fig. 3
Magnetic resonance imaging: a 9-year-old boy with right-sided flank pain with a reconstructed postcontrast image showing an inferior pole "crossing" vessel (artery) (arrow) causing right-sided hydronephrosis

Fig. 4
Magnetic resonance imaging: T2-weighted sequence demonstrating the extent of bilateral pelviureteric junction obstruction, nondilation of ureters, and normal bladder, confirming the obstruction to be at the renal pelvis on both sides

Very complex urogenital anomalies, such as cloacal anomalies in female patients, are usually imaged by US and fluoroscopy in the first instance, but further cross-sectional imaging is invariably required. MRI may offer satisfactory depiction of the anatomy, but frequently, the workup has to occur very soon after birth so that an intermediate management plan can be made before definite surgery can be performed when the infant is older. In this situation, MRI is rarely able to offer sufficient spatial resolution to allow full understanding of the anatomy in these very small patients. In a few very select cases, CT, with a combined distal loopogram and micturating cystogram performed at the time of the scan, as well as contrast intravenously with the scan delayed to excretory phase, can offer exceptional 3D visualization of the entire urogenital tract (Fig. 5). There is little value in a conventional CT alone in these cases, and the routine use of CT is absolutely not advocated.
Fig. 5

Fig. 5
Computed tomography: Reconstructed 3D images showing the complicated anatomy of the urogenital tract in a 3-month-old girl with a cloacal anomaly; the entire urogenital system is demonstrated in one study
Most commonly, infection of the lower urinary tract presents clinically and is treated empirically. However, in a few more complicated cases, US will be performed to look for complications, such as abscess formation or pyelonephritis, within the kidneys and for the presence of underlying contributory factors, such as stone disease or previously undiagnosed structural anomalies. In most instances, US is able to resolve these clinical issues and is clearly the modality of choice for assessing infection (both in the acute stage and at follow-up). If US cannot answer the diagnostic question, further cross-sectional imaging may sometimes be useful. In the acute setting, with a very ill patient and suspected sepsis related to the urinary tract, CT may add further information regarding, for example, abscess rupture or retroperitoneal fluid (or pus) collections (Fig. 6). CT is useful in showing calcification and extrarenal complications in xanthogranulomatous pyelonephritis, if this has not already been confirmed by US. MRI may be of value after the acute episode for demonstrating underlying structural anomalies if these have not been determined by US.
Fig. 6

Fig. 6
Computed tomography: a 15-year-old girl with chronic renal failure on peritoneal dialysis with recent onset of abdominal pain and signs of sepsis. The shriveled right kidney (arrow) is the expected size of both kidneys, but the left kidney shows acute (more ...)
In the acute setting of trauma in children, US is once again the first-line technique in the emergency room. US can quickly demonstrate whether the kidney is still vascularized, if there is physical damage (fracture, laceration, avulsion) of the kidney, and provide some information regarding surrounding complications. If the trauma is believed to be confined solely to the kidney and the child is stable, it may not be necessary to proceed to any further immediate imaging. However, it is frequently the case that these patients have been involved in a complex trauma, and as such, multiple injuries may have occurred. In most cases, major renal injuries are associated with injuries to other major organs, and renal trauma occurs in 8–10% of patients with significant blunt or penetrating abdominal trauma [15, 16]. In this instance, CT is usually performed straight from the emergency room. CT will demonstrate direct trauma to the kidney and to any other intra-abdominal organs and may show retroperitoneal injuries or complications better than US [17]. Typical findings include contusions (shown as ill-defined or sometimes sharply marginated areas of reduced enhancement and excretion), nonexpanding subcapsular hematomas (appearing as a hyperattenuating fluid collection between the renal parenchyma and the renal capsule, at times deforming the underlying kidney), perinephric hematomas (an ill-defined, hyperattenuating fluid collection located between the Gerota fascia and the renal parenchyma), renal lacerations (jagged or linear parenchymal disruptions that can contain fresh or clotted blood), renal lacerations with collecting system involvement (which frequently produce extravasation of urine or contrast agent), and renal segmental infarction appearing as well-delineated, linear or wedge-shaped, often multifocal and nonenhancing areas that extend through the parenchyma in a radial or segmental orientation. Thrombosis, dissection, and laceration of segmental renal arteries are primary causes of segmental infarctions, and such infarctions are frequently associated with other renal injuries. Severe injuries include a shattered or devascularized kidney (which appears nonenhancing, with CTA showing a blind-ending renal artery), ureteropelvic junction (UPJ) avulsions, and complete laceration or thrombosis of the main renal artery or vein. CT of the urinary tract should usually be obtained in severe pelvic trauma prior to surgery. MRI has no indication in the acute setting of trauma. Very occasionally, it may have some value in the follow-up of renal trauma, but in children, this would usually be by US.
Both CT and MRI can give excellent information with respect to normal vascular supply to the kidneys and wider urinary tract and in the context of vasculopathies. US would be the first-line investigation, but if anatomical delineation is required – for example, for surgical planning – then CT or MRI can be performed at the surgeon's and radiologist's discretion. CT will give better spatial resolution with the CT scan being performed in the arterial phase and allows 3D reconstruction of the vascular tree but at a considerable radiation dose. The clinician must be sure that sufficient information cannot be obtained by another method before proceeding. MRI is increasingly able to offer detailed vascular information with no radiation dose, and this should be considered as an entirely viable alternative in cooperative children (Fig. 7). At the time of writing this article, conventional angiography remained the gold standard for demonstrating subtle abnormalities in the renal vasculature, but it is both invasive and carries a relatively high radiation dose. However, in the diagnosis of subtle renal artery stenosis, for small arteriovenous malformations of the kidney, and for tiny aneurysms such as in polyarteritis nodosa or Wegner's granulomatosis, it is still the investigation of choice. It is no longer indicated in the diagnosis or workup of renal tumors prior to surgery.
Fig. 7

Fig. 7
Magnetic resonance imaging: gadolinium-enhanced MR angiography demonstrating arterial anatomy in an 11-year-old girl with a known horseshoe kidney
MRI plays an important role in the workup of children waiting for renal transplant. Whereas initial assessment of their native vessels [aorta, inferior vena cava (IVC), iliac and femoral vessels] may be by US, proceeding to MRI may be necessary if the US is technically inadequate (due to the presence of bowel gas or other structures) or if it is indeterminate. Conventionally, gadolinium contrast agents have been given to best illustrate the vessels, but in patients who are known to be in renal failure (hence the need for transplant), gadolinium is no longer given due to the risk of NSF. In these patients, MR angiography (MRA) is still achieved using tailored sequences [true fast imaging with steady-state precession (FISP) and time-of-flight (TOF) sequences], which obviate the need for intravenously administered contrast. It is also helpful in patients who have had renal transplant and in whom the anatomy may be difficult to demonstrate by US.
Calcification in the urinary tract
Stone disease and calcification relating to the urinary tract in children deserves special mention, as its imaging management differs to that in adults. US is a highly effective imaging tool when looking for calcification (nephrocalcinosis) and calculi within the kidney. Subtle nephrocalcinosis may be demonstrated by using a high-resolution probe when it has not been demonstrated by a conventional linear probe, and the pediatric sonographer should always use both techniques if nephrocalcinosis is being sought. There is no indication to use CT or MRI when diagnosing nephrocalcinosis in children unless there is a specific concern regarding the additional presence of calculi, which may be difficult to delineate by US in the presence of particularly florid nephrocalcinosis.
Children's smaller body habitus allows good visualization of even tiny calculi within the collecting system, parenchyma, and bladder. If the ureters are dilated, US may also show calculi in the upper and lower third of the ureter but remains consistently poor at demonstrating calculi in the middle third of the ureter. In a select group of patients, it may be appropriate to proceed to CT, but CT should not be routine imaging for stone disease children. It is, however, highly sensitive (97%) and specific (96%) for urinary tract calculi and is undoubtedly an excellent technique in this respect [18]. Children who may benefit from CT include those with a high body mass index (BMI) in whom US cannot sufficiently penetrate soft tissues for adequate visualization, those in whom US is not tolerated, children with severe scoliosis in whom there is not a suitable acoustic window to access the kidneys, children who continue to have symptoms of stone disease in which no calculi have been demonstrated by repeated US, and children in whom a history of stone disease is known but symptoms are out of proportion to US findings. It must be remembered that many children will have recurrent calculi, and it is therefore highly undesirable to perform a high radiation dose examination on every occasion for an underlying benign condition with a normal life expectancy. If CT is requested, it should be performed with a low-dose technique and without intravenously administered contrast (which would obscure any calcific focus) [19, 20].
Many tumors may involve the urinary tract depending on the organ of origin and the age of the child. Renal malignancies represent about 6% of cancer diagnoses in children <15 years of age. Wilms tumor is by far the most common of the renal tumors, representing approximately 95% of cases overall and 96% in children <5 years (Fig. 8).
Fig. 8

Fig. 8
Computed tomography showing the extent of a large, left-sided Wilms tumor in a 2-year-old girl with thrombus extending the full length of the inferior vena cava (IVC) and into the right atrium (between arrows)
In all instances, the first imaging should be by US, which can confirm the presence of the mass and can usually (but not always) determine the organ of origin. However, further cross-sectional imaging is indicated for further anatomical delineation, information on tissues characteristics, and to establish staging. In centers with pediatric MRI, this is absolutely the imaging modality of choice: it provides a wealth of information regarding the tumor itself, provides a base-line for follow-up (thus avoiding repeated CTs), and can provide accurate staging. Sequences will typically include T1- and T2-weighted sequences, short-tau inversion recovery (STIR) sequences, apparent diffusion coefficient (ADC) sequences, and postgadolinium contrast-enhanced 3D fast low-angle shot (FLASH) sequences in a combination of axial and coronal planes. ADC sequences are relatively new in abdominal imaging (but have been used extensively in the brain for some time). These sequences give information about how easily water can diffuse in and between cells; thus, a tumor with densely packed cells will return low signal intensity and will appear dark on this MRI sequence. If it, or a part of it, is undergoing necrosis, it will return a higher (whiter) signal intensity. This is especially useful when monitoring a tumor to assess its response to treatment such as chemotherapy and to follow-up for recurrence. MRI can give information as to IVC and renal vein patency (Fig. 8) if this has not already been determined with certainty by US. Detailed MRA may also be performed, if necessary, to allow surgical planning. In centers with no access to MRI, then CT still provides good information, recognizing that it cannot supply tissue-specific information as MRI and that it incurs a heavy radiation burden. Follow-up of treated tumors should be by US where possible, although many cancer protocols determine that MRI (or CT) should be performed at specifically determined intervals.
Renal functional MRI
US, CT, and MRI all provide good anatomic images [21] of the kidney and urinary tract, but MRI (both in adults and children) has developed very rapidly over recent years and has great potential in the near future to change the way the urinary tract is imaged after the initial US. Uniquely, MRI can also give functional information on the kidneys [4, 22], unlike the other cross-sectional modalities. Traditionally, nuclear medicine studies have been employed for this purpose, but they give poor spatial resolution and provide only relative information rather than absolute values with respect to renal function. MRI is therefore alone in being able to give both anatomical and functional information. Functional renal imaging techniques such as contrast-enhanced MR renography [23, 24], and unenhanced techniques such as diffusion-weighted imaging (DWI) and blood-oxygen-level-dependent (BOLD) imaging, have shown considerable promise in evaluating renal function in health and disease. Whereas this is a relatively new area in clinical terms, it is rapidly advancing and crossing over from being a research technique to offering a real clinical alternative to existing techniques for assessing renal function [25]. Technically, it is no different performing this in children than in adults, but – as with all MRI in children – the rate-limiting step for the technique is the child's ability to remain completely still through a long scan without the need for general anesthesia. It is likely, therefore, that it will be incorporated into the repertoire of renal imaging for older children in the reasonably near future but probably not for younger children unless there is a very specific indication.

   Contrast-enhanced MR renography:
   The basis of the technique relies on dynamic contrast enhancement of the kidneys using MRI to monitor transit of contrast material, typically a gadolinium chelate, through the renal cortex, the medulla, and the collecting system. Most gadolinium contrast agents are cleared by glomerular filtration and pass through capillaries and renal tubules, causing renal tissue signal intensity to increase. By analyzing renal tissue enhancement as a function of time, clinically important single-kidney parameters such as renal blood flow [24], GFR, and cortical and medullary blood volumes can be determined and can be plotted graphically to generate various functional parameter curves. Split renal function can be calculated [25]. Current indications in adult imaging include functional imaging in renal artery stenosis and assessing potential allograft dysfunction in the early postoperative period, potentially avoiding the need for biopsy to distinguish between acute tubular necrosis and acute rejection. It should be noted that as this technique relies on administration of gadolinium as a contrast agent, it is not suitable for patients with renal failure, due to the risk of NSF.
   Diffusion-weighted MRI:
   DWI has traditionally been used in imaging stroke victims, as it is very sensitive in detecting acute ischemia. The ADC calculation can be used in vivo for quantifying the combined effects of capillary perfusion and diffusion. This technique was referred to above in tumor assessment; however, it also has applications in assessing renal insufficiency with studies showing good correlation between GFR and ADC values, highlighting the potential role for evaluating renal dysfunction in native kidneys. DWI also appears to have a future role in renal allograft evaluation and renal artery stenosis.
   Blood-oxygen-level-dependent (BOLD) MRI:
   BOLD MRI can be used for noninvasive but direct measurement of renal oxygenation [26]. It exploits the paramagnetic effect of deoxyhemoglobin for acquisition of images sensitive to local oxygen concentration. Again, it has application in the context of renal artery stenosis and renal allograft dysfunction but also in diabetic nephropathy

Imaging of the urinary tract in children relies on US as the first-line imaging modality; however, MRI has an invaluable role to play, with CT playing a lesser part. Considerations specific to children revolve around radiation dose issues with CT and the need (or not) for a general anesthetic in MRI. It is crucial that the clinical question is clearly established and the study chosen is tailored to the specific child after discussion between the clinician and the radiologist. MRI is the technique of choice for imaging tumors and congenital anomalies when these cannot be satisfactorily delineated by US, and it should generally be regarded as an excellent advanced problem-solving technique. CT is indicated in multisystem trauma and in some children with renal calculi. Functional MRI is rapidly developing in the adult world, and some applications are becoming relevant in children. Center-specific expertise may lead to a certain study being performed in one setting versus a different study in another. This factor may be an important consideration in choosing which modality is appropriate. For elective imaging, referral of the patient to a center with pediatric expertise for superior study should be considered, if it is a realistic option. Ultimately, it is the collaboration between the nephrologist and the radiologist that will lead to the best imaging modality for each patient.

Self-assessment questions
(Answers appear following the reference list)

   Which examination has the highest sensitivity for detecting renal-tract calculi in children?
       CT with contrast enhancement
       CT without contrast enhancement
       CT with contrast enhancement and delayed images to show the level of obstruction
       MRI using a T1-weighted sequence
       US in the hands of an experienced operator who is aware of the clinical history
   Which patient cannot have an MRI examination?
       A child with claustrophobia
       A child with end-stage renal failure in whom gadolinium is therefore contraindicated
       A baby 5 days old who is on a ventilator
       A child who had a CT the previous day
       A child with a pacemaker
   Which series has the highest radiation dose?
       Enhanced CT of the abdomen and pelvis with a delayed series
       Enhanced CT of the abdomen and pelvis without a delayed series
       MRI with T1, T2, post-gadolinium TI and ADC sequences, in coronal and axial planes, of the abdomen and pelvis, with a delayed series
       Unenhanced CT of the abdomen only, followed up by unenhanced CT of the abdomen (only) 4 weeks later
       MRI of the abdomen and pelvis followed up by CT of the abdomen and pelvis 6 weeks later
   Which of the following is poorly demonstrated on MRI?
       Renal medulla
       Renal cortex
   Regarding NSF, which of the following is false?
       NSF does not occur in healthy patients with normal renal function
       The risk of NSF is increased in patients with a low GFR
       The relationship between NSF and MRI contrast agents has only been recognized in the last 5 years
       The risk of NSF is not reduced by dialysis
       All types of gadolinium contrast agents pose a similar risk of NSF in patient with renal failure

1. b. CT without contrast enhancement has the highest sensitivity for detecting calculi but carries a heavy radiation dose penalty. It is therefore NOT the first examination of choice in children. US should always be used in the first instance, and CT only when there is still diagnostic difficultly. Contrast may obscure the presence of stones, as it is also of high density (white).
2. e. A pacemaker is generally considered an absolute contraindication to MRI, as it may become deprogrammed or pulse erratically in the strong magnetic field. (In absolutely exceptional cases, a clinical decision can be made to turn some pacemakers off or turn them to fixed-pulse mode). A child with claustrophobia may have MRI under sedation or general anesthetic if clinically indicated. Modern sequences often obviate the need for gadolinium in patients with end-stage renal failure. The age of the patient and the previous imaging history would not affect the clinical decision to request MRI.
3. a. This series involves scanning through the abdomen and pelvis on two occasions. The absence or presence of intravenously administered contrast agent makes no difference to radiation dose. MRI does not involve radiation.
4. c. Calcium (such as in renal calculi) contains no water and therefore does not have protons that are easily influenced by magnetic fields, and as such, it returns almost no signal (signal void) on all sequences and is difficult to detect.
5. e. Not all gadolinium contrast agents are the same. Omniscan and Magnevist are thought to pose increased risk due to the chelate to which the gadolinium is attached, with these compounds being more likely to release free gadolinium ions into the body. Dotarem is currently considered to be the least likely agent to allow release of free gadolinium ions.

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4. Grattan-Smith JD, Jones RA. MR urography in children. Pediatr Radiol. 2006;36:1229–1132. doi: 10.1007/s00247-006-0222-2. [Cross Ref]
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6. Grattan-Smith JD, Little SB, Jones RA. MR urography in children: how we do it. Pediatr Radiol. 2008;38(Suppl 1):S3–S17. doi: 10.1007/s00247-007-0618-7. [PubMed] [Cross Ref]
7. Grattan-Smith JD, Jones RA. Magnetic resonance urography in children. Magn Reson Imaging Clin N Am. 2008;16:515–531. doi: 10.1016/j.mric.2008.04.002. [PubMed] [Cross Ref]
8. Grattan-Smith JD. MR urography: anatomy and physiology. Pediatr Radiol. 2008;38(Suppl 2):S275–S280. doi: 10.1007/s00247-008-0793-1. [PubMed] [Cross Ref]
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19. Kalra MK, Maher MM, D'Souza RV, Rizzo S, Halpern EF, Blake MA, Saini S. Detection of urinary tract stones at low-radiation-dose CT with z-axis automatic tube current modulation: phantom and clinical studies. Radiology. 2005;235:523–529. doi: 10.1148/radiol.2352040331. [PubMed] [Cross Ref]
20. Memarsadeghi M, Heinz-Peer G, Helbich TH, Schaefer-Prokop C, Kramer G, Scharitzer M, Prokop M. Unenhanced multi-detector row CT in patients suspected of having urinary stone disease: effect of section width on diagnosis. Radiology. 2005;235:530–536. doi: 10.1148/radiol.2352040448. [PubMed] [Cross Ref]
21. Kirsch AJ, Grattan-Smith JD, Molitierno JA., Jr The role of magnetic resonance imaging in pediatric urology. Curr Opin Urol. 2006;16:283–290. doi: 10.1097/01.mou.0000232051.66718.34. [PubMed] [Cross Ref]
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Sunday, November 27, 2011

research kidney

XGP is a rare form of chronic pyelonephritis and probably represents
an abnormal immune response to bacterial infection.

urinary tract obstruction -- nephrolithiasis

xanthogranulomatoese Pyelonephritis
xanthogranulomatous Pyelonephritis
Xanthogranulomatous pyelonephritis successfully treated with antibiotics only.

Ciprofloxacin is a broad-spectrum antibiotic that is active against
both Gram-positive and Gram-negative bacteria

Urine typically contains both leukocytes and bacteria. The pH is often
basic because Proteus mirabilis is a urease-producing organism. The
erythrocyte sedimentation rate is frequently elevated.

XGP and renal cell carcinoma have even been observed in the same specimen.

interesting reading
XGP typically presents with non-specific symptoms [5] and laboratory
abnormalities [6] including leucocytosis, increased blood urea
nitrogen and creatinine levels. Typical features that may be found on
CT scan include enlarged kidneys with multiple low-density areas
associated with hydronephrosis, and indications of perirenal
extension. In native kidneys, the cases with diffuse XGP require total
nephrectomy. Partial nephrectomy or medical therapy with antibiotics
could be considered for focal disease.   >> antibiotics

Bei der akuten Pyelonephritis ist die Antibiotikagabe über mindestens
10 Tage[11] zwingend erforderlich. Schwere Infektionen sollten mit
Fluorchinolonen, z. B. Ciprofloxacin, oder mit
Breitspektrum-Cephalosporinen, auch in Kombination mit
Aminoglykosiden, behandelt werden.[11] Zur Anwendung kommen außerdem
Amoxicillin, Piperacillin mit Tazobactam, sowie Imipenem. Wenn möglich
erfolgt die Therapie nach Erreger- und Resistenzbestimmung.

Die perorale Gabe ist zu bevorzugen, wenn es der klinische Zustand des
Patienten erlaubt. In einer Studie mit 141 Patienten war die
intravenöse Gabe von Ciprofloxacin der oralen nicht überlegen

Thursday, August 25, 2011

GMO Killer T-Cells FEVER -Leukemia Cure


Genetically engineered cell offers possible cancer-killing breakthrough
Published: Thursday, Aug. 11, 2011 3:29 p.m. MDT
By Lois M. Collins, Deseret News

Research that changes a type of white blood cell so it's a weapon against cancer cells is being hailed by experts as a potential breakthrough in cancer research.

Scientists at the University of Pennsylvania turned T cells into cancer cell killers in a common type of leukemia using genetic engineering. Experts say it may be possible to engineer T cells to kill other types of cancer, including blood, breast and colon, as well.

The research, part of a very small clinical trial involving just three patients who had advanced cases of the chronic lymphocytic leukemia, is published online this week in the New England Journal of Medicine and also in Science Translational Medicine.

Two of the patients have been cancer-free for more than a year, while the other experienced improvements. The plan now, given such promising results, is to expand the trial and treat other patients, then follow them to see long-term effects, the researchers said. They also hope to test it in other, perhaps more aggressive cancers.

"This is a huge accomplishment — huge," Dr. Lee M. Nadler, dean for clinical and translational research at Harvard Medical School, told the Los Angeles Times. Nadler is credited with finding the molecule on cancer cells that the genetically engineered T cells attack.

The researchers said they added instructions to a virus for creating a molecule that binds to leukemia cells and tells the T cells to destroy them. In the clinical trial, they drew blood from the three patients who had chronic lymphocytic leukemia, infected the T cells with the virus and reinjected the blood back into the patients. The engineered T cells multiplied rapidly and killed the cancer cells, then remained for months. "They even produced dormant 'memory' T cells that might spring back to life if the cancer was to return," wrote the Times' Eryn Brown.

A CBS/Associated Press story said the therapy "resulted in armies of serial killer cells that targeted and destroyed cancer cells, even new cancer cells as they emerged. T cells typically attack viruses that way," but it noted study author

Dr. Carl June, professor of pathology and laboratory medicine at the University of Pennsylvania, said it's the first time it has been turned against cancer.

The study describes what happened after the engineered T cells were reinjected in the patient. After 13 days, "the patient began having chills and low-grade fevers associated with grade 2 fatigue. Over the next five days, the chills intensified and his temperature escalated to 102.5 degrees," they wrote, noting he suffered a variety of miserable digestive symptoms, including nausea and diarrhea. But within slightly more than three weeks of having the modified cells reintroduced, "there was no evidence of (the leukemia) in the bone marrow." Ten months out, when the study was written, that patient remained cancer free.

The researcher believe that each engineered T cell killed 1,000 cancer cells or more. They noted that the engineered cells remained for six months at high levels in the blood and bone marrow and while there they continued to express the chimeric antigen receptor.

Bone marrow transplants have been the best hope for patients suffering from chronic lymphocytic leukemia and have been the only hope for an actual cure. But the side effects have been potentially serious, even fatal, including infections and liver and lung damage. About 20 percent of those who receive such a transplant may die of complications of those side effects, rather than the leukemia that was being treated.

Dr. David Porter, director of the blood and marrow transplant program at the Hospital of the University of Pennsylvania and a study co-author, told the Los Angeles Times that earlier efforts to modify T cells have been disappointing. It was different this time because the researchers added more instructions to the virus telling the cells to "multiply, survive and attack more aggressively."

The National Cancer Institute describes leukemia as "cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream." It says 44,000 new cases are diagnosed each year and about 22,000 people die from the disease. The institute also offers an online guide to the disease and its treatments.

The Mayo Clinic says that the form of leukemia called chronic lymphocytic leukemia affects a group of white blood cells called lymphocytes, which help the body fight infection.

One of the patients, who asked not to be identified, issued a statement through the university. He said chemotherapy worked for years, but it stopped. Now, he wrote, "I'm healthy and still in remission. I know this may not be a permanent condition, but I decided to declare victory and assume that I had won."

Genetically Modified "Serial Killer" T Cells Obliterate Tumors in Patients with Chronic Lymphocytic Leukemia, Penn Researchers Report

(PHILADELPHIA) -- In a cancer treatment breakthrough 20 years in the making, researchers from the University of Pennsylvania's Abramson Cancer Center and Perelman School of Medicine have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells. The protocol, which involves removing patients' cells and modifying them in Penn's vaccine production facility, then infusing the new cells back into the patient's body following chemotherapy, provides a tumor-attack roadmap for the treatment of other cancers including those of the lung and ovaries and myeloma and melanoma. The findings, published simultaneously today in the New England Journal of Medicine and Science Translational Medicine, are the first demonstration of the use of gene transfer therapy to create "serial killer" T cells aimed at cancerous tumors.

"Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected," said senior author Carl June, MD, director of Translational Research and a professor of Pathology and Laboratory Medicine in the Abramson Cancer Center, who led the work. "It worked much better than we thought it would."

The results of the pilot trial of three patients are a stark contrast to existing therapies for CLL. The patients involved in the new study had few other treatment options. The only potential curative therapy would have involved a bone marrow transplant, a procedure which requires a lengthy hospitalization and carries at least a 20 percent mortality risk -- and even then offers only about a 50 percent chance of a cure, at best.

"Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them," says co-principal investigator David Porter, MD, professor of Medicine and director of Blood and Marrow Transplantation. "This approach has the potential to do the same thing, but in a safer manner."

Secret Ingredients

June thinks there were several "secret ingredients" that made the difference between the lackluster results that have been seen in previous trials with modified T cells and the remarkable responses seen in the current trial. The details of the new cancer immunotherapy are detailed in Science Translational Medicine.

After removing the patients' cells, the team reprogrammed them to attack tumor cells by genetically modifying them using a lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19.

Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL tumor cells and normal B cells. All of the other cells in the patient that do not express CD19 are ignored by the modified T cells, which limits side effects typically experienced during standard therapies.

The team engineered a signaling molecule into the part of the CAR that resides inside the cell. When it binds to CD19, initiating the cancer-cell death, it also tells the cell to produce cytokines that trigger other T cells to multiply -- building a bigger and bigger army until all the target cells in the tumor are destroyed.

Serial Killers
"We saw at least a 1000-fold increase in the number of modified T cells in each of the patients. Drugs don't do that," June says. "In addition to an extensive capacity for self-replication, the infused T cells are serial killers. On average, each infused T cell led to the killing of thousands of tumor cells – and overall, destroyed at least two pounds of tumor in each patient."

The importance of the T cell self-replication is illustrated in the New England Journal of Medicine paper, which describes the response of one patient, a 64-year old man. Prior to his T cell treatment, his blood and marrow were replete with tumor cells. For the first two weeks after treatment, nothing seemed to change. Then on day 14, the patient began experiencing chills, nausea, and increasing fever, among other symptoms. Tests during that time showed an enormous increase in the number of T cells in his blood that led to a tumor lysis syndrome, which occurs when a large number of cancer cells die all at once.

By day 28, the patient had recovered from the tumor lysis syndrome –– and his blood and marrow showed no evidence of leukemia.

"This massive killing of tumor is a direct proof of principle of the concept," Porter says.

The Penn team pioneered the use of the HIV-derived vector in a clinical trial in 2003 in which they treated HIV patients with an antisense version of the virus. That trial demonstrated the safety of the lentiviral vector used in the present work.

The cell culture methods used in this trial reawaken T cells that have been suppressed by the leukemia and stimulate the generation of so-called "memory" T cells, which the team hopes will provide ongoing protection against recurrence. Although long-term viability of the treatment is unknown, the doctors have found evidence that months after infusion, the new cells had multiplied and were capable of continuing their seek-and-destroy mission against cancerous cells throughout the patients' bodies.

Moving forward, the team plans to test the same CD19 CAR construct in patients with other types of CD19-positive tumors, including non-Hodgkin's lymphoma and acute lymphocytic leukemia. They also plan to study the approach in pediatric leukemia patients who have failed standard therapy. Additionally, the team has engineered a CAR vector that binds to mesothelin, a protein expressed on the surface of mesothelioma cancer cells, as well as on ovarian and pancreatic cancer cells.

In addition to June and Porter, co-authors on the NEJM paper include Bruce Levine, Michael Kalos, and Adam Bagg, all from Penn Medicine. Michael Kalos and Bruce Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include June, Porter, Sharyn Katz and Adam Bagg from Penn and Stephan Grupp the Children's Hospital of Philadelphia.

The work was supported by the Alliance for Cancer Gene Therapy, a foundation started by Penn graduates Barbara and Edward Netter, to promote gene therapy research to treat cancer, and the Leukemia & Lymphoma Society.



Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

PennMedicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

Penn Medicine, Philadelphia, PA 800-789-PENN © 2011, The Trustees of the University of Pennsylvania

Media Contact Holly Auer  O: 215-349-5659 C: 215-200-2313

Department of Communications (Media Relations) P: (215) 662-2560 F: (215) 349-8312
For the General Public 1-800-789-7366 Contact upenn

Saturday, July 30, 2011

CancerWife had 15 injections of Coley's toxins but then the blog stopped
1.5ml vial with coley's toxins

CancerWife had 15 injections of Coley's toxins
from 9 August 2010 to 9 September 2010
Oasis of Hope Hospital Paseo Playas No.19. Playas de Tijuana (aka Contreras Clinic)
in Mexico, $8000 or more

This is a record of the blogreport until CancerHusband's blog stopped...
They got coley's toxins supply and  now are doing it at home by themselves for no money ... and have to keep quite about it because of doctors, pharma FDA mafia.
0.3ml syringe (originally for diabetes) -- cancerwife did not use a syringe but used a drip, a port, an infusion

The standard  protocol starting dose recommended is  0.001ml

First injection.   (INFUSION actually)

==  DOSE   0.0005ml ==

Coley's Toxins IV #1 - Our adventure begins    
Submitted by CancerHusband on Mon, 08/09/2010 - 21:20

We had brought a large body-sized far-infrared heating pad to warm her, as well as smaller one for her chest. I kept her under blankets and turned up the room thermostat to 80F. We did this to take the edge of the chills and shakes, as well as to reduce energy requirements by the body to raise core temperature.

1.5 hours after infusion, she began experiencing chills. We cranked up the heat, in order to fend off more extreme chills and the shakes. That worked very well. Shortly after cranking up the heat, her chills all but disappeared. Then, 45 minutes after onset of chills, her temperature reached 102.1F.

So then, it seems that our very first infusion, at 1/2 the typical starting dose managed to induce fever! The actual time above 102.5F was probably not more than 15 minutes. So, it wasn't a very strong response, but a good response nevertheless.

Some observations:

    Her pulse peaked at 117
    Her face was flush red
    Her minimum blood pressure was a drop to 102/54 about an hour before the chills happened (during the pre-warming phase)
    She felt some bone pain in the hip and some soreness in the back. These were very minor.

Generally, we felt that our very first Coleys went as well as one could ask for. We achieved fever in the target range and there were no complications! Overall, the entire fever process took about 6 hours, after which she felt 100% back to normal.

==  DOSE   0.0005ml ==

Coley's Toxins IV #2 - Substantial fever attained!  
Submitted by CancerHusband on Wed, 08/11/2010 - 21:46

Today, we stuck with the same 0.0005mL CFIV dosage. We expected that there may not be any fever today because we're using the same dosage as past Monday's. If you remember, Monday's fever broke past the 102.5F barrier for only 15 minutes. Furthermore, the body is supposed to get more tolerant to Coleys so one would expect a lower fever than expected this time.

However.... to our pleasant surprise, today's fever was a robust one. Chills began almost like clockwork at 1 hour after start of infusion (this is what the MBVax documentation also says).

Her temperature hit 102.5F at 45 minutes after onset of chills. Thereafter, the fever was long and robust. In all, it stayed above 102.5F for a full 2.5 hours. Furthermore, it stayed above 103F for over an hour, reaching a peak of 103.5F.

One unexpected side effect today was she experienced a few minutes shortness of breath. We notified the nurse just in case. The nurse seemed to have seen this before and immediately hooked up an oxygen cannula, running at 1.5 LPM.

Generally, we observed that she sweated quite intensely today. This may have been due to the more aggressive pre-warming (higher heat pad settings, higher room thermostat setting, more blankets). To compensate, I made sure that she consumed more oral electrolytes.

So, it would seem that more aggressive pre-warming may potentially have contributed to a more intense generation of fever? An alternate explanation is she wasn't feeling very strong before commencing Monday's first dosage. Perhaps that would be a more apt explanation for today's higher fever (with same dosage).

Summary: Today's was an extremely successful fever. However, we're curious why it was better than Monday's despite staying at the same dose level.

== DOSE 0.0005ml ==

Coley's Toxins IV #3 - Learning to avoid dehydration during pre-heating  
Submitted by CancerHusband on Fri, 08/13/2010 - 21:16

Looking back at today's treatment, we concluded that we have been too aggressive with the heating pads. In our enthusiasm to avoid the chills and shakes that Coley's induces, we've been aggressively pre-heating her to the extent that she began sweating profusely even before the fever started.

This inadvertently led to significant dehydration, which manifested as flushing of face, low blood pressure (as low as 108/43), and requiring oxygen to alleviate shortness of breath.

The doctor had her feet raised and ordered an IV drip of Hartmann Solution to counter the dehydration and hypotension.

She eventually stabilized and the blood pressure rose. Shortly thereafter, she was able to achieve a fever. However, the fever stayed mainly between 101 and 102F. There were only 2 extremely transient peaks where her temperature managed to exceed the 102.5F target threshold. These peaks lasted for a few minutes, dropping thereafter.

It is our conclusion that the significant dehydration probably robbed her body of the necessary energy to mount a proper fever response today. The 2 transient peaks were indicative of her body trying to raise temperature but "running out of steam".

After her fever peaked and died down, she was, as before, able to get up and enjoy a meal. Her appetite was good and she felt normal, except for being a little tired (The picture below is of her enjoying her post-fever dinner).

For the next Coley's, we plan to alter strategy and go easier with the pre-heating. It'll be interesting to see if that doesn't prematurely tire her body out as much, and therefore help her achieve a higher fever.

== DOSE  0.0005ml ==

Coley's Toxins IV #4 - On the right track   
Submitted by CancerHusband on Mon, 08/16/2010 - 21:15

She was rather tired over the weekend. The Issels doctors prescribed IV protein + Magnesium to replenish her (a CBC done on Saturday morning showed that her protein levels had dropped to 5.8 g/dL (normal minimum being 6.0). The doctor had already predicted it may happen before the CBC was done. The doctor said that drops in protein levels may happen when you have fevers. This, by the way, is one of the advantages of doing Coleys at a place that has a long legacy of doing immunotherapy.

Anyway, the doctors think that her tiredness on Sunday was probably due to her body replenishing after the draining fevers. We decided then to stick with the same CFIV dosage (0.0005mL) and see what temperature she'll achieve with less aggressive pre-heating.

As usual, we had our breakfast from 830-930am. However, after last week's experiences, we concluded there was no way that the Coley Fluid infusion would begin on time at around 11am (The MBVax protocol calls for 2 hours of no food prior to start of IV). Thus, I advised her to eat a good breakfast, knowing that she'll have no lunch.

As it turns out, today's Coley's began even later. By the time we got the diluted solution hooked up to her PICC port, it was about 2:00pm. By that time, it was 5 hours after breakfast and she was already getting hungry. I started her on the oral electrolytes to keep her energy up (there's a good amount of sugar in there).

As planned, we kept the heat pad on a lower setting and modulated other variables such as the number of blankets and room thermostat. Our guiding principle was to keep her warm but avoid making her sweat.

Things went slow and there was no indication of chills or fever for quite a while. But about 2 hours after infusion start, her hands began to feel tingly and she felt some light chills. This seemed to be a delayed response as compared to previous weeks, but nevertheless a response. At 4:30pm her temperature broke through to 102.7F and stayed above 102.5 until 6:00pm. As we had hoped for, she experienced no dehydration, no major drop in blood pressure, no need for oxygen, no flushing of the face. We were ecstatic. Furthermore, she only needed to drink a little over 2 cups of the oral electrolyte formula (as opposed to 6 cups last Friday).

Overall, today's fever was a successful one. 1 1/2 hours above 102.5, with a peak of 102.9F. Not a very high fever, but still a good one. One should also note that the fever was significantly higher than last Friday's treatment, although at the same CFIV dose level. This further corroborates our thinking that dehydration robs the body of energy to mount a good fever.

As aforementioned, there were few unpleasant side effects, the primary one being tiredness and fatigue. The main thing though is it seems we've figured out a very important guideline - which is to avoid sweat (and consequently dehydration) during pre-heating.

== DOSE 0.00075mL ==

Coley's Toxins IV #5 - First dose increase (to 0.00075mL)  
Submitted by CancerHusband on Wed, 08/18/2010 - 17:06

Today, we increased the dosage from 0.0005mL by 50% to 0.00075mL. Those of you familiar with the MBVax protocol will note that this is still less than the typical starting dose of 0.001mL. The reason why we're treading cautiously is from previous experience with various drugs and chemo. She just tends to react quite strongly to typical dosages (even those adjusted for body weight).

Coley Fluid infusion started at 12:30pm. The first sign of chills occurred about 45 minutes later. By 3:15pm, her temperature broke through to 102.6F. It stayed there for a little over an hour. The highest point being 102.7F.

Compared to Monday's fever, this one was a tad lower (Monday's highest was 102.9, with 1.5 hours above 102.5 threshold). This may indicate a need to increase the dosage to 0.001ml next.

Also, a new development today was her pulse rate reached a peak of 130 (10 points higher than Monday's highest). This is a first. I notified the nurse who contacted the doctor. The doctor didn't seem concerned but ordered IV hydration. I'm guessing the doctor thinks the elevated pulse is probably due to dehyration.

Overall, she felt pretty good throughout the fever. The primary symptom, again, was fatigue. Again, she had some slight coughing (coming from the diaphragm). The doctor said that it's most likely due to inflammation caused by the fever.

Even though she felt pretty good throughout the fever, she was quite tired out at the end of the day. Not enough energy to go down to dinner so I brought food up from the cafeteria. We'll see how she feels tomorrow.

== DOSE 0.00075mL ==

Coley's Toxins IV #6 - Looks like it's time to increase dosage more aggressively 
Submitted by CancerHusband on Fri, 08/20/2010 - 17:26

Today, it took almost 2 hours before there was any rise in temperature at all. However, she eventually developed fever, although it was clear that the temperature rise was not as fast and as high as previous treatments. She also experienced some light chills at that time.

Three hours after infusion start, she reached 102.6F. This lasted for barely an hour. Also, her peak was 102.7F. She also tolerated the fever very easily and didn't feel much discomfort, except for the fatigue that's always most prominent during fever peak.

As in the past 2 treatments, we kept the heating pads to a minimum and avoided making her sweat before onset of chills of fever. We also observed that she began to sweat during the cool-down phase of the fever (consistent with the MBVax protocol documentation).

As before, the side effects experienced during the fever were

    chills (kept to a minimum using heat pads & blankets)
    achy feeling in hips downwards (intensity 2 out of 10)
    minor one-sided headache (2 out of 10)
    dry cough especially when lying on the side

All the above side effects disappeared after the fever subsided. We also observed something interesting (but not surprising). During the chill phase, if she turned on her side, the shoulder not in contact with the heating pad would start to feel the chills. This would be immediately mitigated by lying on her back against the heating pad.

Again, this fever seemed to be lesser in intensity and duration. By 5 hours after start of infusion, she was all ready to head down for dinner (she never gets to eat lunch during the days when she gets Coleys, mainly to avoid nausea during the fever). She even felt strong enough to take a shower before heading down to the cafeteria for dinner.

Next week, we are considering increasing the dose to 0.002ml. We feel that the increase from 0.0005 -> 0.00075 didn't do all that much, and hence, a further increase to 0.001 may not be all that meaningful.

===== The wife reports on how it feels =======

Coley's Toxins Weeks 1 & 2
Submitted by CancerWife on Sun, 08/22/2010 - 22:37

We had heard and read much about Coley's Toxins and its potential side effects, and now I was to experience it. We want to share my experience with others: how Coley's Toxins actually makes one feel - both immediately during and after treatment. The past two weeks have been like a long experiment. We recorded every sensation I felt during and after the Coley's treatment. Constant temperature, oxygen, pulse and blood pressure measurements gave us more clues on how to ameliorate the side effects.
I am following MBVax's protocol (, which calls for intravenous administration and dose escalation to achieve fevers between 102.5-106F. The frequency of administration is five times for the first 6 weeks, then three times a week for 3 weeks, then two times a week for 6 months or more. I am aiming to do Coley's for a total of six months for maximum effectiveness.
During the first two weeks of Coley's Toxins treatment, I have been receiving intravenous infusions on Mon, Wed and Fri.
(unusable pixelated picture of a a [sic ]vial of Coley's Toxins (not MBVAX vial!) - red because of the Serratia marcescens bacteria)

One of the common side effects of Coley's Toxins is chills and shakes. A way to minimize the shakes and chills is to prewarm the patient before the infusion of Coley's Toxins. This raises the body temperature so the body does not need to shake and generate chills to warm the body up as it responds to the Coley's.
Every time before the administration of Coley's, I lie in bed with blankets over me, and a full-body heat pad underneath. I only turn on the heat pad if I don't feel warm enough. After a few times of Coley's, we realized that it is best *not* to sweat before I reach a temperature above 102.5F. Somehow the sweat drains energy from me, making it difficult for me to hit the high temperatures.

Of the six times that I've had Coley's so far, I have not experienced any shakes. This may be because I am prewarmed, so the body does not need to shake to raise the temperature. I have felt chills though. It feels like a cool breeze along my back. Sometimes it is on one side of my back, going from the top to bottom, or sometimes it goes from left to right, and sometimes it radiates from the center of the back outwards.
Once I feel a chill, I immediately turn on the full-body heat pad. The warmth minimizes the chills. I usually feel 5-10 chills before it stops.
Sometimes during the chills, my bones feel achy.

Once the chills stop, my temperature starts to climb. During this time, I feel hot and fatigued. Usually the volume of my voice decreases, and I feel like keeping my eyes closed. I try to stay warm but not to a point where I am sweating.
I also keep on sipping electrolytes. MBVax recommends making your own electrolytes with sugar, salt and water, as the store bought ones have too much sugar. The amount of electrolyte I need seems to correlate with how much I've sweat.
I have felt headaches during the fever phase. Usually it's only on one side of the head - a dull headache. It usually goes away by the end of the fever and after I take more oral electrolytes.

Flush phase
It's been quite consistent that when I feel I cannot take the heat anymore and throw away the blankets, that is usually when my temperature starts to decrease. I also feel much warmer and start to sweat more.

After the fever
When my temperature drops to 100-101, I usually feel well enough to eat dinner with a good appetite (see picture below - my dinner after the fever). I don't eat during the fever, so I skip lunch. I am usually a bit fatigued, and my bones feel achy and tired.
The next day I usually feel 100% back to normal. A few times I felt flushed and hot, but that only lasted about 10 mins or so.
An interesting thing is that if I get Coley's on Friday, I feel totally fine on Saturday, but I start to feel a bit fatigued and my bones ache a bit on Sunday.

===== END wife report  =======

== DOSE  0.002ml ==

Coley's Toxins IV #7 - A long but sub-optimal fever   DOSE  0.002ml
Submitted by CancerHusband on Mon, 08/23/2010 - 22:24

Today's fever was uneventful but interesting. We went with an increased dose of 0.002ml thinking that an increase from 0.00075ml to 0.001ml wouldn't do much. We were right.

The chills began 1 hour after infusion start like clockwork. However, 3 hours after infusion start, her temperature was still 101.2F. It became apparent that today's was not going to a very high fever.

The fever stayed mostly between 101 and 102F for a good 3 hours. It briefly touched 102.5F but only for a few minutes.

In general, she was pretty fatigued for the duration of the fever. All other symptoms were consistent with previous fevers - bone pain in the hips, tingling in the fingers, very slight chills (with heating pad), one sided headache, elevated pulse. These were all minor and they all resolved quickly as the fever subsided. However, the fatigue seemed to linger a little longer than usual.

The lingering fatigue might be explained by her anemia. Her Hemoglobin, MCV and MCH were low even before we started on Coley's. The MBVax protocol explains that Coley's may cause anemia itself due to competition in the bone marrow for increased white cell production. Furthermore, it seems that fever itself can lead to a drop in iron levels. Well, today, we got the results of her CBC and Serum Iron test done last Saturday.

    Her iron levels are 33 ug/dL (normal being 50-180).
    Hemoglobin has improved a little to 10.8 (from 10.1)
    MCV declined slightly from 73 -> 72
    MCH declined slightly from 24 -> 23.9
    RDW is high at 18.7

It looks as like this is likely iron deficiency anemia. However, the Issels program does not recommend iron supplementation (iron through food is OK). Nevertheless, we have ordered Floradix iron supplements from the US via mail and hope that it'll make it to the hospital in a couple of days. Strictly speaking, we're not on the Issels treatment plan, but rather, we're following the MBVax protocol. And that protocol does call for Iron supplementation.

I also wonder if this anemia would compromise her body's capability to achieve higher fevers. Regardless, we will try to fix this and hope it'll resolve soon.

On a separate positive note, her total WBC is still at 7500/mm3 (if you remember, it doubled from 4000 to 8000 after the first 3 fevers. It has never been this high, ever, since chemo). In addition, a new development is her lymphocyte count is now at 2000/mm3. This is a first ever since chemo. Her highest has been around 1000/mm3 for the past 2 years since radiation and chemo.

Well, it looks like we'll have to increase dosage again the next time.

== DOSE  0.002ml ==

Coley's Toxins IV #8 - Another sub-optimal fever at 0.002mL
Submitted by CancerHusband on Wed, 08/25/2010 - 23:00

After some deliberation, we decided not to increase the dose level. Instead, we wanted to see if a higher fever could be obtained by increasing external heat instead. After all, we felt that the previous fever (#7) was quite a good one, despite the sub-optimal temperature. It's duration was long and she was quite fatigued after that fever.

Well, as it turns out, increasing the external heat did not lead to a higher fever. Instead, she again developed a fever mainly between 100-101F. This was noticeably lower and of shorter duration than the previous one. She also tolerated it easier and was less fatigued. She did experience some chills but very light ones and very short. She had bone aches from the hip down to the legs.

Our conclusion: increasing external heat did not seem to substantially affect her ability to achieve higher fever. It's clear that we need to escalate dosage.

== DOSE  0.003ml ==

Coley's Toxins IV #9 - A better fever but could be higher. A lingering (but very infrequent) cough.
Submitted by CancerHusband on Sat, 08/28/2010 - 16:37

Today we increased dosage again to 0.003ml. The fever was uneventful and predictable. It was somewhat better than the last one. However, it wasn't as high as we'd hoped for. The peak was a tad below the desired 102.5F threshold. So we'll need to increase again next Monday.

Well, so far, it looks like her Coley fevers are becoming quite predictable and boring -- and that's the way we like it. It'll be interesting though to see if we're able to reach the higher temperatures - and to see how how she tolerates them.

Again, the side effects have been quite minimal. The fatigue, increased heart rate, bone aches that occur during the fever all disappear as the fever subsides. And they are very minor to start with.

The only side effect that seems to somewhat linger on after fevers are gone are a slight cough. It's very infrequent -- we're talking maybe 20 coughs over the entire day.

The doctors think this could be due to general inflammation that Coley's induces. The worse case scenario would be the cough is caused by potential lung tumor(s). Our last scan on June 7th showed two tiny 2mm and 3mm nodules that are suspicious. They were too small to biopsy. Sarcomas can grow very fast. Thus, there's always the possibility that if those were tumors, they may have grown large enough to be symptomatic.

Even so, the cough may not be a bad thing. It could signify the vaccine having positive effect on potential tumors. There's a clear correlation between the frequency & intensity of coughs and the fevers. Coughing is more frequent during fevers - and more so during the fever peak. Regardless, let's hope the cough is due to something else.

===== The wife reports on how it feels =======

Coley's Toxins Week 3
Submitted by CancerWife on Sun, 08/29/2010 - 10:02

This week I had two increases in dosage - to 0.002mL and 0.003mL. Neither dosages gave me sustained fever above 102.5F. Most likely I'm developing some tolerance, so there will be more dose escalation next week.

We learned this week that if I don't sweat much during the fever, I feel more fatigued after the fever ends. This happened on Coley's #7 - I had to rest my head on the dining table during dinner time that night! Thus, for Coley's #8 and #9, we cranked up the heat pad when my fever started to subside. This caused me to sweat more and I had more energy after the fever ended.

Another thing we noticed is my hands have gotten darker. (No, I have not been tanning here in Tijuana :-)) The only other time this happened was during chemotherapy, when I received doxorubicin and ifosfamide. It is a normal side effect of the chemo. It could be that somehow Coley's is causing side effects from chemo to reoccur. Reactivation of "old injuries" has been observed in other patients receiving Coley's.

===== END wife report  =======

== DOSE 0.004ml ==

Coley's Toxins IV #10 - Still not good enough
Submitted by CancerHusband on Mon, 08/30/2010 - 20:43

Today's dosage was again an increase to 0.004ml. This was because last Friday's fever wasn't very high and maxed out at 102.4F for a short duration.

Today's was even lower. It maxed out at 101.9F and for not very long either. I would estimate that the average fever was about 101F. It wasn't very difficult to tolerate and recovery as the fever subsided was very quick.

So it seems clear that her body is developing resistance to the toxins. Let's hope that dose escalation will be able to break this. We will ask the doctors if it would be appropriate to skip the next dose level and go straight to 0.006ml.

== DOSE 0.006ml ==

Coley's Toxins IV #11 - Breaking tolerance
Submitted by CancerHusband on Tue, 08/31/2010 - 21:53

Today, we increased the dosage from 0.004ml -> 0.006ml. We did this because it was becoming apparent that her body is developing tolerance to Coley's Toxins. We felt that increasing to 0.005 wouldn't do too much based on previous fever curves.

Increasing to 0.006ml was probably the right choice. We clearly noticed that today's chills were much more apparent (even with the heat pad). This was more in line with the robust fever from IV#2. Also, the chills occurred about 45min-1 hour after infusion start. This was followed by rise in body temperature shortly after. In contrast, fevers 8, 9 and 10 were slow to happen.

Today's peak was 102.7F. This is above the 102.5F threshold. We were happy about that. However, one interesting thing we noticed is that it dropped off rather quickly (in comparison to robust fever #2).

I wonder what it'll take to re-create a sustained fever. Do we merely need to hit a high enough dose? Or could it be that her body has become more efficient at neutralizing the Toxins? Hmm...

== DOSE 0.009ml ==

Coley's Toxins IV #12 - 104 Fahrenheit
Submitted by CancerHusband on Thu, 09/02/2010 - 17:38

Today, we decided to be a little daring and upped the dosage from 0.006ml -> 0.009ml (a factor of 50%). We decided to do this based on her response from fever #11 where we increased from 0.004->0.006ml. That 50% increase resulted in a clearly better fever, but still not quite high enough.

We got the go ahead from the doctors here. The fever was a little slow to start. Normally, the stronger fevers seemed to manifest chills 1 hour after infusion start. This one was later at almost 2 hours.

The historical records really are true - that robust fevers are clearly associated with more intense chills. Today's chills didn't last that long -- only about 30 minutes. However, it was clear that they were more intense compared to previous ones. Similarly, fever#2 resulted in intense chills as well. Today's chills were continuous and occurred in many places - in her shoulders, arms, legs -- and a new location -- behind her head! I suppose the pillow under her head prevented the heating pad from warming up that area. Nonetheless, it was interesting to that this is the first time chills have occurred there.

Once the chills subsided, her temperature began to rapidly rise. It reached 103.4F about 15 minutes after the chills subsided. Shortly thereafter, it peaked at 104F. This is the first time it's hit that high.

Interestingly, her fever didn't sustain at high levels for long. As in fever#11, it began to drop quite soon after peaking. Nevertheless, it was still a good, robust fever, reaching the highest peak ever.

Other observations:

    The past 2 fevers have not resulted in much aching in her long bones and hips. This occurred quite noticeably in earlier fevers. If those aches were indicative of bone marrow growth, it would be interesting to see how her WBC counts this Saturday are.
    As before, she began coughing 30 mins after infusion of Coley's started. This time, the coughing was more frequent. Not more intense, just more frequent. Her temperature was normal at that time, but her face looked a little flush/red. Later on, during the post-chills phase when her temperature began to rise, I noticed that her cough also became quite frequent. Subsequently, it diminished as her fever decreased.


    We just spoke with another patient here at the Issels ward. She received Coley's subcutaneously into her arm. She developed a fever of 104F (40C) for 5 hours! Boy, was that a major fever! After the fever broke, she had profuse sweating. The interesting point is that other Issels patients have also reported very long lasting fevers, 8 hours or more in some cases, that had to be stopped with Tylenol. That may be an advantage of subcutaneous administration (the downside being pain at injection site along with possibly unreliable development of fevers due to variable amount of Toxins entering the bloodstream?).

== DOSE 0.009ml ==

Coley's Toxins IV #13 - Revamped fever charts. Figuring out the dry cough.
Submitted by CancerHusband on Sat, 09/04/2010 - 16:31

I've programmed a chart that's hopefully easier for folks to see how the Coley's Toxins fevers progress over time. I did it mainly for ourselves to be able to visualize how a given fever compares with the prior one - and also how it compares with the "best" fever thus far. The best one she's had is fever #2. It was long and protracted, and she stayed well above 102.5F for a good 2.5 hours.

Now, back to today's fever. Since the prior fever was a good one that reached 104F, we chose to stay at the same dose level. That's what the MBVax protocol calls for.


The chills took a while to develop - but they did come eventually. The chills were frequent but very gentle this time. Mainly a light cool sensation on the back, arms, back of head. Remember now - she has a full body far-infrared heating pad along with blankets and a second chest heating pad. These are turned on and put in place right from the start, before the chills. Again, the purpose is to ward off violent chills and shakes which happen when the body resets it desired temperature point upwards and tries to generate internal heat.

The gentle chills foretold of a lesser fever. Still, she managed to hit 103.1F (39.5C). In all, I estimate that she stayed above 102.2F (39C) for a good 1.5 hours. The plot of this fever (#13) versus the prior one shows a more or less similar curve, except with a lower peak. This indicates her body is beginning to develop tolerance to this dose level (hence the lower peak). We will need to think about whether to increase dosage for next Monday.

Figuring out the cough

For today's infusion, we worked with the doctor here at Issels and decided to eliminate their pre-infusion vitamins and minerals (all prior Coley's infusions were preceded by an IV infusion of B vitamins and minerals to strengthen the body. This was mixed into 500ml saline). For today, all that was given was 250ml of pure saline. The reason we did this was to see if the pre-infusion was contributing to the dry cough that happens each time she gets Coleys.

The doctor also listened carefully to her lungs before infusion, and during the fever, when the cough started up. Here's what we found:

    Her lungs sounded very clear before infusion (when there was no cough)
    During this fever, the cough was noticeably less than the prior fever (#12). Three differences in today's fever are
        Smaller volume of infused liquid (250ml versus 500ml)
        No B vitamins + multi-minerals
        No Coley's dose increase (hence a less intense reaction than #12)
    During the fever cough, the doc listened again very carefully and noted the following:
        When breathing normally, her lungs sound clear -- i.e. no evidence of general bronchial constriction that may be indicative of allergic reaction due to Coleys.
        However, when coughing, it does sound like a "wheeze" (only during the cough).

The doc suggests one possibility is a small tumor that might be pressing on a nerve. Coley's causes tumors to inflame. This might be an explanation for why the cough comes during infusions. The doc didn't think it was a pleural cough. The doc said that a pleural cough would be triggered when one breathes in deeply -- and would manifest in a sharp spasm/pain in the sides. (In her case, she does cough whenever she breathes in deeply, but there are no sharp pains).

Is the dry cough due to general inflammation?

Another possibility that we're pondering is general inflammation caused by Coley's. We've been observing minor but noticeable aches and pains here and there - like on a finger tip, behind the knee cap, in the hip. These generally occur during the peak of the fever.

We can't help but to make an association with an episode 2 years ago when she was given a single shot of Depot Lupron before chemotherapy. This led to all sorts of pains and aches on her chest, ribs, jaw, scalp, shoulder... and it also caused a dry cough. All our doctors and oncologists were totally stumped. CT scan, X-ray, nuclear perfusion tests, blood tests were negative. The ER doc suggested that her cough could be caused by inflammation in the pleura surrounding the lungs. In the end, we did a little experiment, based on the hunch that what we were seeing was generalized systemic inflammation. So she took a single dose of ibuprofen, and that IMMEDIATELY killed the cough and aches and pains. It was like magic - really. Coleys almost definitely causes temporary inflammation. So, you can see why we might believe that the dry cough, aches and pains that we're seeing are due to a generalized inflammatory process.

===== The wife reports on how it feels =======

Post-fever appetite: Coley's #13
Submitted by CancerWife on Sat, 09/04/2010 - 21:32

During my Coley's treatments, I eat breakfast around 8:30am, skip lunch, then I eat dinner after the fever subsides. Today I decided to eat some fruit during the fever, as I was getting quite hungry. I had a plum, then a banana. That wasn't quite enough for me, so after the fever came down, I went down to the cafeteria and asked for a snack. I had two pieces of cake (healthy cake with nuts and fruit) and a cup of apple juice.

Then came dinner time. We went out to a nearby restaurant with other patients. I had a bowl of tortilla soup (with avocado, homemade cheese, tortilla strips) and ostrich steak. The ostrich tastes like very lean beef. I've been low in iron, so I've ordered ostrich a few times already.  I had room even after that! So, I ended the meal with a large piece of carrot cake. After all that eating, I wasn't even stuffed!

I'm in awe that I have very good appetite each time after Coley's. It's such a stark contrast to the time when I had chemo (doxorubicin and ifosfamide). My appetite got worse and worse with each round of chemo, and my weight kept on dropping. With Coley's, I have no problems eating dinner afterwards, and as you can see for today, I can eat quite a large meal!

===== END wife report  =======

== DOSE 0.009ml (+) ==

Coley's Toxins IV #14 - Another good fever.
Submitted by CancerHusband on Mon, 09/06/2010 - 20:08

Today's fever was another good one. She stayed above 102.2F for a good 2 hours.

The fever curve was quite similar to fever #2. The maximum temperature was 103.6F (39.8C). However, you'll notice that it took a little longer to reach its peak. However, once reached, it seemed to stay up there a little longer than recent fevers.

Observations for today's fever:

    Chills lasted for about 20 minutes but were very mild
    The dry cough was even less than fever #13. It occurred only when she would lay on her side. And even so, they were sparse. Could it be that it's resolving??
    She had some numbness and sensitivity in her left hand today -- more so than previous fevers.
    She had a dull headache (mainly center front) and also a transient sharp pain in the back of her head (left side). These are were quite minor (in terms of intensity).

Other than that, I would classify today's a robust fever, with weak chills. Lasted on the longer side at relatively high temperatures.

OK to eat during fever?

The MBVax protocol warns not to eat before Coley's, as well as during the chill phase. I need to check again, but my impression was not to eat during fever as well. It would make sense too, since digestion would probably be impaired during fever.

Well, today we decided to experiment a bit. Whenever she gets Coley's, she doesn't get to eat lunch. And today's Coley's started dripping at around 12:45pm. So, by 4:00pm, she was pretty hungry. Thus, even though she had just reached a high temperature of 103.6F (today's peak), I decided to let her eat a little fruit. We went slow and she had no problems. No nausea. Eventually, she probably ate a full cup of fruit (grapes, canteloupe, papaya). Later on, I gave her a cookie to eat as well.

Interesting observation regarding dilution

Coley's Toxins has to be diluted before being administered intravenously. Today, the Coley's Toxins vial was almost empty. It probably had 0.2ml left, of which 0.1ml was removed, and then diluted. We noticed that it seems a little darker red (more concentrated). This could happen if the vial is not shaken thoroughly each time before extraction. This would result in the remnant solution becoming more and more concentrated. Therefore, even though we kept at 0.009ml, we probably got more than that today.

Possible reactivation of old injuries by Coley's Toxins

We've heard from MBVax that they've observed Coley's reactivating "old injuries". Secondly, the doctors here at Issels believe that Coley's mobilizes toxins and possibly any remnant chemo from the body. They believe it is very important to have a good sweat during/after Coley's (in order to get rid of these toxins).

Well today, we observed something reminiscent of a side effect from chemo 2 years ago. Chemo caused callouses to develop on her fingers, and also some skin peeling. Today, before Coley's started, she observed some of that on her left thumb. She doesn't think it's due to soap because it's only on the left thumb and not on any of the other fingers. A few hours after the fever, she observed little bumps on the thumb. These are all pretty minor, but still noteworthy.

Postponed until tomorrow
Submitted by CancerHusband on Wed, 09/08/2010 - 18:21

Early this morning, she woke up with a slight burning sensation across the upper middle area of her chest. Later on, she felt a slight heavyness in her chest. It would eventually get better by evening time.

The doctors listened carefully to her lungs. They said her lungs sounded clear.

One possibility is she might be fighting off an upper respiratory infection. It's been going around here in the small ward where we are. There are no open windows here so it's hard to get real fresh air.

Our standard protocol when we see the first signs of an upper respiratory infection -- and which has worked very well for us the past 2 years --  is to immediately supplement with the following for no more than 3 days:

    High dose Vitamin D3 - 90,000IU / day for 3 days max
    Sambucol (Black Elderberry extract) - 2-3 Tbsp / day (better than Tamiflu)
    Lactoferrin (between 500mg - 1000mg, twice daily)

Generally, we try to minimize supplements during Coley's. One can do as much research as possible and choose supplements that may be complementary to Coley's. However, there's always a risk of negative interaction. For example, taking high dose fish oil is anti-inflammatory and there is the risk of muting the immune response (which we don't want with Coley's!!). Likewise, there is the theoretical risk for Vitamin D3, Curcumin, and maybe even EGCG. These are all based on our own research trolling through pubmed research articles. Therefore, we intend to take the above supplements only for 3 days maximum.

We'll see how she fares tomorrow. We agree with the doctors that it makes sense to postpone Coley's and re-evaluate come tomorrow.

== DOSE 0.012ml  ==

Coley's Toxins IV #15 - A good fever given the circumstances
Submitted by CancerHusband on Thu, 09/09/2010 - 21:25

This morning, she woke up and felt good enough to to Coley's. There wasn't any "slight burning sensation" in the chest. Neither was there any noticeable heavyness. However, she did have some light yellow phlegm that had to be cleared with some difficulty. So we're thinking that the symptoms she felt yesterday were the beginnings of an upper respiratory infection after all. Perhaps our standard high dose Vitamin D3 - Sambucol - Lactoferrin mix nipped it in the bud, as it has done so reliably for the past 2 years. Only time will tell.

As usual, she received an infusion of saline + B vitamins + multi-minerals. She's received this with almost every Coley fever. This is standard operating procedure at Issels. The actual Coley's was infused beginning at 1pm. It's now 7pm and she's finally gotten up and gone to wash up.

Mild chills

She experienced fleeting chills 1 hour post infusion start. Then, nothing for a while until about 2.5 hours post infusion start. The second occurrence of chills ended up being only about 15 minutes. As usual, they were mild, which we assume is due to our pre-warming with the far infra red pad.

Even milder cough

If you remember, the last Coley's was characterized by a rather mild cough. We were wondering/hoping then that her fever associated cough was beginning to resolve. Well, today's cough was even milder. When coughed only a few times the entire day. There were no spontaneous coughs. They had to be triggered with deep breathing. This happened only after the fever peaked.

Fever strength and duration

The fever peak wasn't very high. But we're not too surprised. We did increase dosage to 0.012ml. We did so because we feel that the previous dosage of 0.009ml was in actuality higher due to the more concentrated remnant fluid left at the bottom of the vial. So, we wanted to stay at the "same dosage" as before. And we took a best guess and estimated it to be 0.012ml, not daring to go higher.

Today's fever peaked at 102.7F. It hovered above the lower threshold of 102.5F for just about an hour and 20 minutes. So, while it wasn't a very high fever, it was a relatively protracted one.

Overall, we were both quite pleased with today's fever given that she was a bit under the weather to start with. An interesting observation:- after the fever, she observed that her lungs felt clearer -- perhaps the fever helped smack down any upper respiratory tract infection! ..... we'll see.....

Back home for the weekend. A four day break.
Submitted by CancerHusband on Sun, 09/12/2010 - 11:32

We're back home for the weekend. She just had a routine Chest CT done and we're waiting for the film lab to burn the disk. As a result of our little haitus, it'll be 4 days break in between Coley's Toxins treatments (we'll resume Coley's next Tuesday).

The MBVax protocol talks about loss of tolerance to Coley's Toxins. Patients who stop Coley's for more than a week are supposed to go back to the beginning and start at 0.001ml all over. Ours will be 4 days - not quite 1 week. We might consider reducing dosage. We'll have to discuss this with the Issels doctors.

Well one thing's for sure, we're enjoying the food back home and eating as much as we can! (The food at Oasis is really quite good, but it's primarily vegetarian)

An unexpected delay in treatment
Submitted by CancerHusband on Tue, 09/14/2010 - 18:56

Sunday night, she suddenly came down with spontaneous shaking chills and high fevers - three of them in the ensuing 24 hours. Her highest registered temperature was 105.6.

After the first fever subsided, we thought it was most likely some viral infection that was resolving. However, when the second one hit, we cancelled the flight back down to San Diego (no way she could walk with the severe chills). We waited for the chills to subside and the fever to spike.

The second fever seemed to resolve after some time. I wanted to take her to the urgent care clinic but she wanted to have a meal. After the meal, the chills hit yet again, and her temperature spiked again.

We took her to the Stanford University ER where they did blood cultures, X-rays, urine samples. They administered broad spectrum IV antibiotics empirically, as there was no obvious infection (no flu like symptoms, no burning during urination, no diarrhea etc).

For many hours the ER doctors had no clear idea what could be causing the fevers. I had to explain to about 6 different physicians our adventures for the past 5 weeks in Mexico.

After about 14 hours, they found evidence of bacterial contamination in her PICC line. They removed the line and sent it for further analysis, hoping to isolate the primary bacterial strain. By that time, she was already beginning to feel much better.

It may take a few days (or more) to take care of this infection. This will cause a delay in her treatment. We won't be going back down to Mexico until this is completely taken care of. Sorry.... but there'll be no Coley's fever graphs until then ....

Delay in Coley's while waiting for Graves' to subside
Submitted by CancerHusband on Sat, 11/27/2010 - 14:23

We're still waiting to resume Coley's. Unfortunately, there's been a resurgence of her Graves' disease (which started in April 2010). One of the symptoms that we have to be careful about is the elevated heart rate due to Graves'. We're trying to get that under control before considering resuming Coley's.

There's the possibility that Coley's caused her Graves' disease to re-surge. However, there are other potential causes including the Pseudomonas sepsis itself, or a recent bad allergic reaction triggered by her PICC dressing.

Our best guess is that she may have had Graves since 2008 (or at least some tendency towards autoimmunity). Why do we think this? Mainly because she experienced a major unexplained bout of systemic inflammation from a single dose of Lupron in 2008, and then half-side body numbness after a single Pneumovax shot in mid 2009. These occurrences were unexplainable and self-limiting. A neurologist-oncologist we consulted with at Stanford concurred with us that the Pneumovax reaction was most likely an autoimmune attack on the nervous system.

There are also historical references to Coley's being used to ameliorate autoimmune diseases such as rheumatoid arthritis. Obviously, we hope that Coley's was not the cause of the Graves' resurgence. Regardless, we will have to proceed carefully in the future to ensure that it does not exacerbate Graves' too much.