Nutritional Optimization of the Cancer Patient

Joshua Novak M.D.

Conflicts of interest • None

Malnourished Cancer Patient • Higher rates of hospital readmissions • Longer hospital stays • Reduced quality of life 1

Gastrointestinal Symptoms • 50 % of patients with advanced cancer

– early satiety – 71% – Taste change - 60% – Anorexia - 56% 2 – Require Surgery or Parenteral Nutrition- 5% 3

• treated with radiotherapy

Weight loss • 50 % of cancer patient have weight loss at

time of presentation • Highest in pancreas and gastric cancers

– (0ver 80%)

• Early assessment is key • Malnutrition in cancer patients is associated

with increased morbidity and mortality • Anti-cancer treatments less effective

Oral Intake • Changes in taste and appetite • Learned Food Aversions

– Due to learned aversion during toxic chemotherapy.

• Depression – 58% of cancer patients can have symptoms of

depression 58

Cachexia • Chronic, progressive, involuntary weight loss

which is poorly or only partially responsive to common nutritional support – Anorexia, early satiety – Decreased nutritional intake – Metabolic alteration due to activation of systemic

proinflammatory processes – Insulin resistance, increased lipolysis – Increased protein turnover with loss of muscle mass – Increase cytokine induced metabolic alterations

– Prevent weight gain during nutritional support

Cachexia • Cachexia 7

– Body weight loss >10% – Nutrient intake <1500kcal/day – C-reactive protein >10mg/L

• Malnourished cancer patients have a poor response to chemotherapy 8

• 4-24% of terminal cancer patients die due to cachexia • Why poorer outcome from treatment in patients with

weight loss? – Receive significantly less chemotherapy and develop more

toxicity rather than any specifically reduced tumor responsiveness to treatment.

Cachexia • Andreyev et al - retrospective review of outcomes of patients with

or without weight loss and treated for locally advanced or metastatic tumors of the esophagus, stomach, pancreas, colon or rectum

• 1555 patients treated over a 6-year period • Patients with weight loss vs without weight loss

– Received lower chemotherapy doses initially – Developed more frequent and more severe dose limiting toxicity—

specifically plantar-palmar syndrome (P < 0.0001) and stomatitis (P < 0.0001).

– Decreased overall survival (P < 0.0001, hazard ratio = 1.63) – Decreased response (P = 0.006) – Quality of life and performance status (P < 0.0001). – Received 1 month less treatment (18%) (P < 0.0001). – Patients who stopped losing weight had better overall survival (P =

0.0004).

Gastrointestinal Tract Malignancies • Mechanical obstruction and intestinal

dysfunction • Malignant obstruction develops slowly over

time • Gastroparesis and intestinal pseudobstruction

– Paraneoplastic syndrome from immune-mediated destruction of enteric nerve plexus destruction

• Post operative ileus • Medication induced ileus

Malabsorption • Radiation toxicity to GI mucosa

– Radiation enteritis and colitis – 10% of patients with radiation enteritis who were dependent on

Parenteral Nutrition ( PN) had malabsorption as the reason for PN 12

• Pancreatic exocrine insufficiency from pancreatic resection • Fistulae (tumor invasion, surgery or radiation) lead to

malabsorption – Up to 85% occur in the post operative setting. 12

– Degree of malabsorption depends on location of fistula • Small bacterial overgrowth- damage to enterocytes

– Gastric resection vs control - loss of acid barrier • 77.6%vs 6.7%, (P < 0.01).13

– Surgically created blind loops

Nutritional Intervention • Oral Diet Therapy • Enteral Nutrition (EN) • Paraenteral Nutrition (PN) • Pharmacologic Therapy

Oral Diet • Non-invasive • Ravasco et al. 14

– Colorectal cancer patients receiving radiotherapy – Found patients who received nutritional counseling were

able to maintain their adequate nutritional status compared to those left at an ad lib diet

– At radiotherapy completion, energy intake increased in Nutritional counseling and protein supplementation (P < 0.04)

• Counseling > protein supplementation (p = .001) • Decreased in Ad lib (P < .01). • Protein intake higher in counseling (p < 0.007) • At 3 months, counseling group maintained nutritional intake and

the other groups returned to baseline. • Long term follow up adequate nutritional status was maintained in

91% of patients ( nutritional counseling)(p < 0.002).

Oral Diet • Recent Meta-analysis demonstrated that

dietary counseling alone was not able to improve the quality of life of patients (emotional function, loss of appetite) 14,15

– Malnourished patients who received dietary counseling plus nutritional supplements gained more weight than either alone

– Nutritional intervention had no effect on mortality

Enteral Nutrition • ASPEN guidelines

– recommend nutritional support not routinely used in non-malnourished cancer patients undergoing surgery

• Indicated in the malnourished patient undergoing chemotherapy, radiation, or surgery who is anticipated to have decreased intake for prolonged periods of time

• Placement of feeding tubes – Bypass obstruction in stomach or intestines – Overcome oropharyngeal dysphagia – Allow a GI tract that is limited to have nutrients.

Enteral Access • Percutanous Endoscopic Gastrostomy (PEG) • PEG/J • Nasojejunal Feeding Tube • Direct Percutanous Endoscopic Jejunostomy

(DPEJ) • Surgically placed Gastrostomy or Jejunostomy

Enteral Access • Percutanous Endoscopic Gastrostomy with

Jejunal extension (PEG/J) 34 – 93% success rate with placement – lasts 55 days – 33% dislodgement of J extensions

• Nasojejunal tubes 35 – Easy to place

• Up to 40% become dislodged • Decrease with using a nasal bridle ( 32% vs 6.5%) • Can deliver nutrition distal to a post-operative fistula and

allow for improved closure, with decreased cost compared to PN.36

Transnasal Endoscopy • Allows for the establishment of gastric and

small intestinal enteral access in patients – Gastric outlet obstruction – Gastroparesis – Altered Surgical Anatomy

• Roux-en-Y Gastric Bypass • Billroth I & Billroth II • Partial and complete gastrectomy

Transnasal Endoscopy • Success rate in the small bowel ranges

between 90% to 95%.16-19

• Success rate for post-pyloric placement approaches 95% to 100%.16,17

• Placement in the proximal jejunum decreases to approximately 84% to 90%.17,19

• Even lower success rates (25% to 35%) for placement distal to the ligament of Treitz.19

• Migration proximally out of the small bowel occurs in 12.5% to 16% of cases 20,21

Okeefe S.J., Rolniak S., Raina A., Graham T., Hegazi R, Wagner P. Enteral Feeding Patients with Gastric Outlet Obstruction. Nutr Clin Practice 2012 27:76-81

Percutanous Endoscopic Gastrostomy (PEG)

• Used to provide enteral access for nutrition support or decompression in setting of gastric outlet obstruction

• Palliation in malignancy bowel obstruction • 2270 patients (retrospective) who underwent

PEG for malignancy (excluding Head and Neck and thoracic malignancy) 24

– 66% were nonhematologic malignancy – 90.5% had active malignancy at time of procedure

• Receiving chemotherapy, surgery or XRT • 44% had metastatic disease • 53.4% had surgical resection, 21.7% had radiation • 72% chemotherapy

Percutanous Endoscopic Gastrostomy • 73% received PEG for enteral access • 27% for obstructive symptoms • 98.9 % success rate • In hospital mortality 19.6% (median 54 days)

– ICU admission, lower preoperative albumin • All cause mortality 19.6%

– Major PEG complications- 10.2% Aspiration, PEG tube dislodgment, Post operative bleeding, cardiac arrest

– Minor – 11.2% infections , tube feeding intolerance, ileus • 7/15 or 46.7% of those who were on preoperative TPN

without a bowel obstruction achieved independence from TPN

PEG in Esophageal Cancer • Traditional Pull Method carries risk of

metastatic seeding abdominal wall ( 1%) – Median time to occurrence occurs approximately

8 months post procedure 25

• Recent meta-analysis peristomal metastasis, associated with less well differentiated tumors (usually SCC)26

• Carries increased risk of bleeding • Mechanical complications

PEG • Chadha et al., retrospective study of head and

neck, and esophageal cancers undergoing T- fastener Gastroplexy. 27

– 356 patients, 82% had stage III-IV malignancy – 21% esophageal, 16.3% tongue, larynx 15.1% – Cellulitis 8.6%, abscess at PEG site 4% – NO deaths related to PEG – No cases of tumor implantation – Infection at PEG site in Pull technique has been

reported to be as high as 36% (19) • Patients often immune compromised and malnourished

Pancreatic Surgery • 40% - malnutrition prior to pancreatic

surgery28

• 4-7% weight loss prior to surgery 28

• 7-15% weight loss in total gastrectomy 29,30

• 7-10% weight loss in esophagectomy and pancreatectomy patients post-operatively 31

– No randomized large trials addressing early EN after pancreatic surgery comparing type of formula, timing of enteral nutrition, nutritional status, type of procedure and type of feeding device.

Pancreatic Surgery • 68-92% of patients with pancreatic cancer have

exocrine insufficiency. 32,33 • Continues post operatively in 65-80% of patients

33 • Check Fecal elastase-1

• <200 ug/g shows deficiency • Replete with pancreatic enzymes • Viokase (can be crushed and flushed down

jejunostomy tube if needed) – Open others, mix with warm water and bicarbonate

for 15 min, then flush down tube mixed with water • Caution with nasojejunal tube • 2500-10,0000 units of lipase per kg/day

Post-operative Enteral Nutrition • Early Enteral Nutrition is beneficial

– Enteral nutrition preserves gut function – Randomized prospective Multicenter Study

• Esophageal, pancreatic and gastric malignancy ( not metastatic disease)

• All patients had feeding Jejunostomy tube • Traditional care ( IV Fluids until resumption of oral diet) • Intervention group- enteral nutrition resumed within 12 hrs of

surgery – Continued until 75% of caloric needs met orally

• Length of stay was 16 days in enteral vs 19 days in control group P=0.011 – No difference in readmission – Wound infections 7% vs 16% (p=0.017) – Delayed gastric emptying 0 vs 7% (p=0.031)

• Further supported by systemic review 55

Indications for DPEJ • High risk for aspiration • Status-post gastric resection • Status-post esophagogastrectomy • Gastric outlet obstruction • Obstructed or non-functioning

gastrojejunostomy • Gastric dysmotility

Adapted from Shike M, Latkany L. Direct Percutaneous Endoscopic Jejunostomy. Gastrointest Endosc Clin N Am 1998;8:569–80.

DPEJ • First described Shike in 1987 • Modification of the Percutanous Endoscopic

Gastrostomy (PEG) tube • Provides direct long term enteral access to the

jejunum. • Provides a wider lumen tube (16Fr-20Fr) than a

surgically placed or nasoenteric jejunostomy tube – Less prone to clogging

• Placement distal to the ligament of Treitz likely decreases the risk of aspiration. 56,57

Direct Percutanous Endoscopic Jejunostomy

• Esophagectomy or prior gastric surgery limit the endoscopist’s options to effectively place a standard PEG tube.

• Placement of a PEG tube in a partial gastrectomy increases the risk of complications as well as aspiration

• Surgical placed Direct jejunostomy tubes carries a morbidity rate of 6-25% along with the risks of surgery.37

PEG/J vs DPEJ • Retrospectively compared PEG/J vs DPEJ from

January 1996 to May 2001 at the Mayo Clinic • DPEJ- 56 patients (20 Fr tube) vs PEG/J -49

patients (20 Fr G-tube/ 9 Fr jejunal extension). • 6 months following tube insertion were

reviewed • 5 patients with a DPEJ required endoscopic

reintervention vs 19 with a PEG/J for tube dysfunction. (p < 0.0001) 38

Placement of DPEJ in Patients with Complications after Esophagectomy

• Post-operative leaks following esophagectomy – NPO with TPN

• Retrospective analysis of 25 patients with post-esophagectomy complications were referred for DPEJ placement39 – 21 (84%) successful placement – all weaned off TPN – 15 were discharged home on enteral nutrition – 10 had removal of PEJ at a mean of 131 days ( range

20-281 days) • No major complications

TPN in the cancer patient • 25-30 kcal/kg /day • Fat

– Efficient energy source in cancer patients – 1g/kg/day ( soybean lipid emulsions) due to liver

toxicity – Mixed LCT/MCT emulsions and olive oil based more

promising • Can provide 30-50% of daily total energy

• Glucose- – Limit amounts to lower infectious risk of

hyperglycemia – Can cause positive water balance

TPN • Water- Restriction of water advised

– Cachexia- expansion of extracellular volume – Glucose reduces renal sodium excretion , loss of extracellular fluid decreases 40

– Loss of intracellular water and solutes - affect hypothalamic osmoreceptors cells to stimulate the ADH release at levels at subnormal levels 41

– Peritoneal carcinomatosis- excess water, glucose and sodium can lead to ascites

– ESPEN guidelines – total water volume of fluid and sodium <30ml per kg/day – No formula for estimating the water requirement is scientifically validated

• Protein- – Optimal nitrogen supply cannot be determined – 1g/kg/day – 1.2-2g/kg/day 42,43,44 – Most patients do not require a special formulation ( ie glutamine) – Found in lung cancer patients, with moderate cachexia, had insulin resistance,

altered protein anabolism, which was stimulated to near normal function by hypoaminoacidemia.

TPN in Cancer • Systemic review of Randomized control trials

(2001) – No benefit but possible harm when PN was given as

adjunct to chemotherapy in patients who were not malnourished or with decreased hypophagic 45

• Skikora et al. – Retrospective review of 30 esophageal cancer patients – Unable to maintain oral diets but received TPN during

neoadjuvant therapy – TPN patients tolerated higher total dose of

chemotherapy, similar outcomes compared to patients maintaining oral diet. 46

Paraenteral Nutrition • Both the European Society of Parenteral and

Enteral Nutrition (ESPEN) and American Society of Parenteral and Enteral Nutrition( ASPEN) Guidelines; – “the routine use of PN during chemotherapy is not

recommended. However, if patients are malnourished or they are facing a period of longer than a week of starvation and where enteral nutritional support is not feasible, PN is recommended.”

• Patients who develop gastrointestinal toxicity from chemotherapy or radiation therapy. 47,48,49

– “short-term PN is usually better tolerated (and efficient) than EN to restore the intestinal function and to prevent a nutritional deterioration”.

Summary • Nutrition Support is important in the

malnourished cancer patient or when patient has prolonged NPO status.

• Need to recognize and treat malnutrition early • Enteral is always preferred when not

contraindicated

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