Tackling the Conundrum of Cachexia in Cancer

[D.ap]

Olga had mentioned a condition, a term, I was not familiar with and I found this bullentine refering to the condition of cachexia.
I copied and pasted the authors reason , interest for writing the article as it touched my heart.




A Note from the Writer

The genesis of this story was the death of my brother-in-law, Gene, in April 2011. He had been diagnosed with metastatic lung cancer less than 2 months earlier.

The last time I saw him, we watched The Andy Griffith Show. Despite the multitude of offerings on cable, he always preferred repeats of old sitcoms and cop shows.

Although not a large man, Gene was naturally strong and rugged. His handshakes always hurt. As we sat on the couch watching Andy and Barney and Aunt Bee bumble through yet another comical calamity, I was shocked by the dramatic change he had undergone. He was easily 25 pounds lighter. Standing up was difficult. His skin was yellow, his face gaunt, his voice raspy, his eyes cloudy.

A week later, my brother-in-law was too weak to get out of bed on his own. Having shed even more weight, Gene had to be carried to that same couch. Not long after, with only his wife and 12-year-old daughter nearby, he was gone.

As far as my sister can recall, his doctors never used the word “cachexia.” I had heard the term and had a general idea of what it is. But Gene’s passing prompted me to learn more about cachexia and the state of research on this devastating condition. This article is a result of that work.

—Carmen Phillips

http://www.cancer.gov/ncicancerbulletin/110111/page5

NCBI concensus-2011 the meeting of the minds-by the way a great resource to find answers to you ASPS questions

http://www.ncbi.nlm.nih.gov/pubmed/21296615

[D.ap]

For those of you who are up to the challenge
A look at cachexia on the physiological view

http://physrev.physiology.org/content/89/2/381

[D.ap]

I certainly hope that none of us have to face this dilemma
I was researching low glycemic diets and Cachexia and came upon
"The skinny of Cachexia "
Very very clinical
I felt this to be very important to anyone considering chemo to be made aware of-

Prognosis
"The prognostic sign of cachexia is alarming. In cancer patients, weight loss documented prior to initiating chemotherapy predicts a shortened survival than those who had maintained weight (7). In nursing home residents, long-term patients losing 5% or more of his or her body weight have a 10-fold increase in mortality over 6 months compared to those who gain weight over a 1 month period (8). This indicates that if any intervention can be effective to reverse or stop weight loss, the physician should employ them early. Unfortunately however, a meta-analysis found that nutritional supplementation alone does little to decrease mortality or complications (1)."

http://www.clinicalcorrelations.org/?p=1285

[Olga]

Yes, Deb, this is why I always feel uneasy when we start to discuss the popular anticancer diets here - they often associated with the weight loss for the patient and in the long run it is unknown if the dieting brings an overall benefit or harms the patient - considering that many of the cancer patients have to undergo surgeries and chemo-therapies. In y opinion they could be better off by simply trying to maintain their stable weight and to lower the pro-inflammatory factors.

[D.ap]

Yes, Deb, this is why I always feel uneasy when we start to discuss the popular anticancer diets here - they often associated with the weight loss for the patient and in the long run it is unknown if the dieting brings an overall benefit or harms the patient - considering that many of the cancer patients have to undergo surgeries and chemo-therapies. In y opinion they could be better off by simply trying to maintain their stable weight and to lower the pro-inflammatory factors.

I agree with you 100% Olga.
The sight of a patient looking gaunt and appearing listless is enough to make a medical professional let alone the family feel afraid. Diet should always be the for front goal.
Grasping for straws or looking for a snake oil to help a patient rid themselves of cancer shouldn't be sought after unless there is at least some well founded research.

This is an paper from a Sept 1, 2014 NLM from NIH on "Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia"


The abstract:
Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165433/

[D.ap]

Abstract

Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting ever-growing interest in the field of obesity, but could also be an interesting and innovative alternative for treating cachexia. This article reviews the evidence linking the features of malnutrition, as defined by the Global Leadership Initiative on Malnutrition [low body mass index (BMI), unintentional body weight loss, low muscle mass, low appetite, and systemic inflammation] and the gut microbiota in human adults with cachexia-associated diseases, and shows the limitations of the present research in that field with suggestions for future directions.

Keywords: gut, gut microbiota, metabolism, cachexia, metagenomic

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751326/

[D.ap]

Abstract

Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting ever-growing interest in the field of obesity, but could also be an interesting and innovative alternative for treating cachexia. This article reviews the evidence linking the features of malnutrition, as defined by the Global Leadership Initiative on Malnutrition [low body mass index (BMI), unintentional body weight loss, low muscle mass, low appetite, and systemic inflammation] and the gut microbiota in human adults with cachexia-associated diseases, and shows the limitations of the present research in that field with suggestions for future directions.

Keywords: gut, gut microbiota, metabolism, cachexia, metagenomic


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751326/

[D.ap]

Cancer cachexia prevention via physical exercise: molecular mechanisms


Abstract

Cancer cachexia is a debilitating consequence of disease progression, characterised by the significant weight loss through the catabolism of both skeletal muscle and adipose tissue, leading to a reduced mobility and muscle function, fatigue, impaired quality of life and ultimately death occurring with 25–30 % total body weight loss. Degradation of proteins and decreased protein synthesis contributes to catabolism of skeletal muscle, while the loss of adipose tissue results mainly from enhanced lipolysis. These mechanisms appear to be at least, in part, mediated by systemic inflammation. Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia.

Keywords: Exercise, Physical activity, Cachexia, Muscle wasting, Cancer, Resistance training, Aerobic training, Inflammation


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684702/

[D.ap]

“Although cachexia is most commonly associated with terminal stages of cancer, weight loss also commonly occurs in the early stages of the disease, with 17/20 patients with pancreatic cancer displaying a median weight loss of 14.2 % of pre-illness weight at the time of diagnosis resulting in a significantly reduced body mass index [8]. Studies also suggest that the rate and amount of weight loss are important factors in diagnosis and treatment of cancer, with poorer treatment outcomes being noted in patients with weight loss. This may be attributable to patients experiencing weight loss receiving significantly less chemotherapy and developing greater toxicity to treatment [7]. Therefore, a case can be made for trying to attenuate or prevent weight loss occurring upon diagnosis and tackling the effects of cachexia in the early stages of disease.

Several molecular mechanisms have been proposed to explain the pathways leading to the progressive muscle wasting seen in cachexia.“


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684702/

[D.ap]

Our sons success story , back in 2016, in rising above significant weight loss .

From 134 down to 95 lbs, then back up to 130s.

Never give up.

viewtopic.php?p=10340#p10340

Love to all in this sarcoma fight ,

[D.ap]

Augmentation of Cancer Cachexia Components With Targeted Acupuncture in Patients With Gastrointestinal Cancers: A Randomized Controlled Pilot Study

Abstract

Introduction: Patients with gastrointestinal (GI) cancer-associated cachexia are at risk of high morbidity and mortality. This randomized single-blind pilot study compared the complementary use of targeted acupuncture (TA) with nontargeted acupuncture (NTA) for halting cachexia symptoms. Methods: GI cancer patients with cachexia undergoing chemotherapy were assigned to receive 8 weekly sessions of either TA (n = 15) or NTA (n = 15) following a specific acupuncture protocol. Bioelectrical impedance analysis and weight were measured weekly. Biological markers, including C-reactive protein, prealbumin, tumor necrosis factor-α, lactate dehydrogenase (LDH), leptin, and ghrelin blood levels were determined at specific intervals. Results: Prealbumin levels and fat-free mass were significantly higher in the NTA group at the end of the study, but remained stable in TA group. TA group had significantly lower (230 IU/L vs 288 IU/L, P = .04) LDH at the end of the study, but elevated tumor necrosis factor-α levels (13.15 pg/mL vs 9.24 pg/mL, P = .04). The absolute blood leptin and ghrelin levels decreased in the TA but remained stable in the NTA group. Both groups maintained weight, but the TA group trended toward weight gain during the last 2 weeks of the study. No adverse events related to acupuncture were reported. Conclusions: TA using predetermined, reproducible points may provide benefits to some patients with GI cancer cachexia by normalizing metabolic dysregulation. Elevated ghrelin levels are indicative of insulin resistance, which can lead to increased muscle loss represented by increased LDH activity in the NTA group. The pilot study provided completion rate and effect size for the primary outcome measures for a larger study. A longer treatment duration may be required to further refine these findings.



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416748/

[D.ap]

Abstract
Cancer cachexia is characterized by the loss of lean body mass with or without the loss of fat and is associated with increased susceptibility to treatment related toxicities, decreased quality of life, functional impairment, and increased cancer-related mortality. Uncontrolled symptoms which impair nutritional intake, metabolic derangements including elevated energy expenditure and increased catabolism, and chronic inflammation contribute to the development of cancer cachexia. Weight loss in cancer patients is not readily reversible by conventional nutritional support. The definition of cachexia and sarcopenia are evolving with time, as well as the assessment of weight loss in cancer patients. Clinicians should assess all cancer patients regardless of history of weight loss for risk for malnutrition at presentation and periodically throughout the trajectory of illness-pre-cachectic, cachexia, and refractory cachexia stage. For cancer patients with weight loss, assessments of BMI and percentage weight loss, symptoms which impact nutritional intake, quality of life, physical function, biological markers, energy expenditure, and body composition are ideally needed in order to measure cachexia and implement therapeutic interventions.

Keywords: Cancer cachexia; body composition; malnutrition; sarcopenia.

https://pubmed.ncbi.nlm.nih.gov/30525765/

[D.ap]

Mechanisms of Cancer Cachexia

For those of you who are up to the challenge
A look at cachexia on the physiological view

Abstract

Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the α-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NFκB. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-α, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment.

http://physrev.physiology.org/content/89/2/381

[D.ap]

For those of you who are up to the challenge
A look at cachexia on the physiological view

http://physrev.physiology.org/content/89/2/381

Olga please delete above post !

[D.ap]

Yes, Deb, this is why I always feel uneasy when we start to discuss the popular anticancer diets here - they often associated with the weight loss for the patient and in the long run it is unknown if the dieting brings an overall benefit or harms the patient - considering that many of the cancer patients have to undergo surgeries and chemo-therapies. In y opinion they could be better off by simply trying to maintain their stable weight and to lower the pro-inflammatory factors.

I agree with you 100% Olga.
The sight of a patient looking gaunt and appearing listless is enough to make a medical professional let alone the family feel afraid. Diet should always be the for front goal.
Grasping for straws or looking for a snake oil to help a patient rid themselves of cancer shouldn't be sought after unless there is at least some well founded research.

This is an paper from a Sept 1, 2014 NLM from NIH on "Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia"


The abstract:
Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165433/