Is this the future of cancer treatments?
Fast accurate aggressive attack on unsuspecting tumour cells using gentle agents!
https://drive.google.com/file/d/0B10BiJHPKeH8VldHdGxlQ2NqSjZwM1F6NzNBQXpsNEVqcVlj/view?usp=docslist_api
Dear friends
Above is my private tumour biology report that will drive my therapy plan. Its one reason why i did laproscopic abdominal surgery these results different to blood circulating tumour cells.
The other reasons were peritoneal port installation and additional tumour samples to erlangen uni and dr nesslehut for a few innovative options regarding dc vaccine design options.
Our tumours hold our death and life in there hands. Our job is to unclench there fingers and snatch our life back!
So fresh is best. My sample in lab hamburg uni the next day and now targetted therapy starts tomorrow.
Im relying dr steffan genius and hitting tumour genes and I'll stick to my immunotherapies but now i have some finesse in generation of antigen and can mix and match cytotoxic regimes .
I doubt they have anything this comprehensive in the usa. Please please let ne known
I'm trying to stress a point that medical arrogance is deadly and i have a very open mind and like to travel . My basis is i meet lots of patients from all over usa who say they did the best and i meet them here in Germany.
Its just my opinion based on tragic anecdotes. Im comfortable navigating the excellent services the Germans have.
I need to learn german.
Oh i made the 6.5hour drive munich to rheine thanks to a new iron infusion that's given me heaps of energy.
Today i did bloods urine stools saliva for full hormone profiles.
These results may be the missing link in the remission puzzle.
And tonight i finished my gcmaf yogurt by adding fresh organic colostrum.
So tonight i measure presleep temperature as the difference to basal an old german prognostic indicator. It makes sense.
Note to self the heavy iron therapy may suit high dose vit c and or artemisia. I'll do cancer markers and basic bloods.
Note no mention virus or gcmaf in metavectum but il2 yes. I know ecct not tested. I asked maybe one day.
Understanding diarrhea in detail
http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/diarrhea.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC95756/
Its sad when we learn from others suffering but viral infection with inf gamma implies onc viral mediated stroma tumour cell damage and a breaking of tolerance
Understand my anemia
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573441/#!po=6.93431
My immediate pickup has implications and i wonder my glucose and keytones today
The role of intravenous iron in the treatment of anemia in cancer patients
H.Tilman Steinmetz
Additional article information
Abstract
Anemia is a major cause of morbidity in cancer patients resulting in poor physical performance, prognosis and therapy outcome. Initially, erythropoietin-stimulating agents (ESAs) were supposed to be the treatment of choice but about one third of patients turned out to be nonresponders and meta-analyses provided evidence of an increased risk of mortality if used excessively. This along with the successful use of intravenous iron for anemia in patients with chronic kidney disease prompted seven clinical studies evaluating the efficacy of intravenous iron as an adjunct to ESAs and four additional studies using intravenous iron only for anemia in cancer patients. These studies confirmed a superior response if ESAs are combined with intravenous iron and revealed iron only to be a useful option in patients with mild and absolute iron deficiency (AID). Currently, best treatment decisions for anemia in cancer might be based on measurements of serum ferritin (SF), transferrin saturation (TSAT), soluble transferrin receptor (sTfR), ferritin index (FI = sTfR/log SF), hypochromic reticulocytes (CHR) and C-reactive protein (CRP). However, there is still an urgent need for trials investigating diagnostic approaches to optimize therapy of anemia in cancer patients with iron and/or ESAs.
Keywords: anemia of chronic disease, cancer, hemoglobin, iron deficiency
Introduction
Anemia is a major cause of morbidity in cancer patients [Barrett-Lee et al. 2005; Birgegard et al. 2006]. Low hemoglobin (Hb) levels in cancer patients were shown to correlate significantly with poor physical performance [Ludwig et al. 2004; Barrett-Lee et al. 2005; Birgegard et al. 2006; Steinmetz et al. 2011], prognosis and therapy outcome [Fein et al. 1995; Dubray et al. 1996; Glaser et al. 2001;Littlewood et al. 2001; Waters et al. 2002]. There are multiple causative factors including absolute iron deficiency (AID) which may result from chronic bleeding due to gastrointestinal or gynecological lesions, blood loss from surgery, nutritional deficiencies, anemia of chronic disease (ACD), myelosuppressive effects of chemotherapy or metastatic infiltration of the bone marrow limiting erythropoiesis [Rizzo et al. 2002; Grotto, 2008]. Even in the absence of overt anemia, iron deficiency is already associated with impaired physical function, weakness and fatigue which all abate upon iron therapy [Verdon et al. 2003; Brownlie et al. 2004].
Anemia as major cause of morbidity in cancer took center stage with the approval of erythropoiesis-stimulating agents (ESAs) in 1997. At that time one did not think of functional iron deficiency (FID) in cancer patients yet and AID was generally considered of minor importance. Consequently, diagnostic procedures were not developed but therapy was initiated if three conditions were met: (1) diagnosis of cancer, (2) chemotherapy and (3) low Hb levels (< 10 g/dl). Accordingly, the first treatment guideline for cancer-associated anemia in 2002 was primarily a ‘how to use ESA’ guideline [Rizzo et al. 2002]. Only as the sixth of eight recommendations the guideline stated: ‘Baseline and periodic monitoring of iron, total iron-binding capacity, transferrin saturation, or ferritin levels and instituting iron repletion when indicated may be valuable in limiting the need for epoetin, maximizing symptomatic improvement for patients, and determining the reason for failure to respond adequately to epoetin. There is inadequate evidence to specify the optimal timing, periodicity, or testing regimen for such monitoring’. The ESA-dominated view on anemia did not change with recent guideline revisions and diagnostic procedures of anemia have not been specified at all [Bokemeyer et al. 2007; Rizzo et al. 2010a, 2010b] until the guidelines of the National Comprehensive Cancer Network (NCCN) [NCCN, 2012]. As a consequence, laboratory diagnostics are still hardly used prior to ESA therapy in daily practice [Ludwig et al. 2004; Mitchell, 2010; Steinmetzet al. 2011]. Only about 50% of physicians make use of laboratory measurements and most use ferritin only.
Routine practice of triggering ESA treatment of cancer-related anemia based on chemotherapy and low Hb-values only [Steinmetz et al. 2008] has resulted in overall response rates of about 50–60% and the need for blood transfusion has remained high, at about 20–30%. Moreover, during recent years, evidence has been increasing that aggressive ESA treatment as well as blood transfusions may increase all-cause mortality [Spahn et al. 2008; Bohlius et al. 2009] although no such evidence is available if ESAs are used according to the label with target Hb levels between 11–12 g/dl [Glaspy et al. 2010].
The poor response rates to ESA therapy alone and the positive experience with intravenous iron in chronic kidney disease prompted the first study of the combination treatment of ESAs and intravenous iron in cancer patients [Auerbach et al. 2004]. This was followed by six additional studies using iron as an adjunct to ESAs and by four studies using even iron alone in anemic cancer patients. In parallel, the understanding of the pathophysiology of cancer-related anemia has grown substantially [Grotto, 2008] and the detection of hepcidin opened new insights into the regulation of iron metabolism and hematopoiesis [Krause et al. 2000; Park et al. 2001; Goodnough et al. 2010; Thomas et al. 2011]. Consequently, the ACD which has already been known to cause anemia in cancer patients prior to the era of ESAs [Cash and Sears, 1989] came to the fore again [Weiss and Goodnough, 2005] whereas the effect of chemotherapy stood back. With the rediscovery of the concept of ACD the role of iron has changed too. While during the early ESA years iron was used in AID only, the FID described in ACD may explain benefits of iron also in patients with normal or even elevated total body iron. This review focuses on when and how to use iron in cancer-related anemia.
Pathophysiology of anemia in cancer and derived diagnostic tests
Based on WHO criteria [de Benoist et al. 2008] the definition of anemia is relatively simple: Hb <12 g/dl in nonpregnant women and Hb <13 g/dl in male subjects older than 15 years. However, the problem of anemia in cancer is complex and it is not only challenging to identify causes in any given patient, but also to evaluate the relevance of single factors in general. If indicated by a careful anamnesis, initially bone marrow infiltration, hemolytic anemia, renal insufficiency and vitamin deficiency should be ruled out by bone marrow aspiration, measurement of serum levels of lactate dehydrogenase (LDH) and haptoglobin, of creatinine clearance and endogenous erythropoietin, and of vitamin B12 and folic acid, respectively (Figure 1). However, the diagnosis of iron deficiency is not as easy, as one needs to discriminate AID and FID [NCCN, 2012].
Figure 1.
Proposal of a diagnostic and treatment algorithm (incorporating the diagnostic plot of Thomas and Thomas [2002]). ESA: erythropoietin-stimulating agent; FID, functional iron deficiency; CRP, C-reactive protein; ACD, anemia of chronic disease; AID, absolute ...
AID is a common cause of anemia in cancer patients, most often provoked by bleeding or iatrogenic blood loss, less frequently for dietary reasons. Low values of the erythrocyte indices major histocompatibility complex (MHC), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) indicate diminished iron incorporation. Most often serum iron (Fe) is low in AID, but strongly varies with inflammatory reactions; moreover, it might be low in FID too. The most important parameter to assess whole body iron is serum ferritin (SF) which is the intracellular storage protein of iron; 1 µg/l SF corresponds to about 8–10 mg of iron stored. AID is defined as SF <30 µg/l and decreased saturation of serum transferrin (TSAT) <15% [NCCN, 2012]. Unfortunately, SF is an acute phase protein. Consequently during an inflammatory reaction, serum levels increase and there is no longer a clear-cut SF threshold indicating AID; however, SF levels <100 ng/ml make AID very likely and are therefore predictive of a good response to Fe iv, without using ESA [Auerbach et al. 2010; Steinmetz et al. 2011]. Alternatively, intracellularly stored iron might be detected through staining of bone marrow smears which is not very practical though. However, the combination of SF, C-reactive protein (CRP), soluble transferrin receptor (sTfR), and low Hb-content of reticulocytes (Ret-Y, CHR) enables the detection of AID [Thomas and Thomas, 2002] even though SF levels might be >1000 µg/l [Steinmetz et al. 2010].
FID is a major contributor to ACD and accordingly also quite prevalent in cancer-associated anemia [Ludwig et al. 2011]. FID in cancer is most often provoked by tumor cells that interact with the immune system and by this cause a chronic state of inflammation along with the release of pro-inflammatory cytokines, such as interleukin-6 (IL-6) or tumor necrosis factor (TNF). In the clinical setting the extent of inflammation could be assessed through measurement of CRP, which is closely related to the serum IL-6 level. Cytokines foster the release of hepcidin, a peptide hormone and key regulator of iron homeostasis [Weiss and Goodnough, 2005]. Hepcidin blocks the membrane-tunnel protein ferroportin which normally transfers iron from the intracellular stores to transferrin, the transport protein in