Table 61Parenteral vs enteral nutrition: cancer

Bibliographic referenceStudy TypeEvidence levelNo. of patientsPatients characteristicsInterventionComparisonLength of follow upOutcome measuresEffect sizeComments (including source of funding)
Baigrie et al 199616RCT1+97 patients
ETF: n= 50
TPN: n= 47
Patients undergoing oesophagectomy or gastrectomy.

Gender (M/F):
ETF: 30/20
TPN: 28/19

Age:
< 60 years old:
ETF: 19
TPN: 18

> 60 years old:
ETF: 31
TPN: 29

Malnourished:
ETF: 17
TPN: 17

Not malnourished:
ETF: 33
TPN: 30
TPN administered through 16 G CVC.

TPN started from the first postop day.
ETF through a 16 G catheter jejunostomy.

ETF started on the third post-op day with infusion of 5% dextrose. Osmolyte HN was commenced on day four and over the following 48 hours was increased to 100 mL/h. Feeding was continued until patients were able to tolerate an oral diet of 2000 calories per day.
Until dischargeETF : n= 50
TPN : n= 47
Catheter-related morbidityTotal (n=num. of complications) :
ETF :n= 20
TPN : n= 21
[Not significant]

(TPN group had major morbidity complications : septicaemia secondary to catheter infection n=7, axillary vein thrombosis n=2)
Non- catheter related morbidityLife-threatening complications :

- Anastomotic leak (major)
ETF :n= 3
TPN :n= 3

- Respiratory failure :
ETF : n= 3
TPN : n=6

- Pulmonary embolus :
ETF : n=1
TPN : n= 1

- Renal failure :
ETF : -
TPN : n=1

- Myocardial infarct/arrhymia :
ETF : n=1
TPN : n= 2

- Cerebrovascular accident :
ETF : n=1
TPN : n=1

- Aortic false aneurysm :
ETF : -
TPN : 1

Total :
ETF : n= 9
TPN : n=15

Non-life threatening complications :

- Anastomotic leak (minor)
ETF : n=2
TPN : n=6

- Gastric outlet obstruction (temporary)
ETF : n= 1
TPN : n= 1

- Pneumotorax :
ETF : n= 2
TPN : -

- Deep vein thrombosis :
ETF : n=1
TPN : -

- Wound infection/ haematoma :
ETF : n= 2
TPN : n= 3

- Recurrent laryngeal nerve palsy :
ETF : -
TPN : n=1

Total :
ETF : n= 8
TPN : n= 11
MortalityTotal :
ETF : n=4
TPN : n=6

- Respiratory failure :
ETF : n=1
TPN : n=3

- Myocardial infarct/arrest :
ETF : n=1
TPN : n=1

- Anastomotic leak (fatal) :
ETF : n=2
TPN : n=1

- Cerebrovascular accident :
ETF : -
TPN : n=1
Bozzetti et al 200141RCT1+317 patients randomised

ETF: n=159

PN: n=158
Cancer patients undergoing elective surgery with a weight loss greater than or equal to 10% of the usual bodyweight in the past 6 months.

Mean age (SD):
ETF: 64.8 (10.8)
PN: 64.1 (9.8)
Sex (M/F):
ETF: 93/66
PN: 92/66

Proportion of bodyweight lost (%,mean SD): ETF: 14.2 (4.0) PN: 13.4 (3.4)

Exclusion criteria: less than 18 years old, hepatic dysfunction (Child-Pugh>2), renal dysfunction (serum creatinine concentration > 265.2μmol/L, haemodialysis, or both), or cardiac dysfunction (New York Heart Association functional class >III, stroke history); had Karnofsky performance status less than 60; were pregnant; had ongoing infection; or had intestinal anastomosis of the large bowel without a diverting stoma.
Nutrition regimens started at 0800 h the morning after surgery and were continued until patients were able to tolerate adequate oral food intake.

All patients had a CVC placed during operation.

PN nutrition included electrolytes, vitamins, and trace elements according to current standards.
Nutrition regimens started at 0800 h the morning after surgery and were continued until patients were able to tolerate adequate oral food intake.

ETF: either jejunostomy feeding catheter or nasojejunal feeding tube placed during surgery, according to the preference of the centre.

All patients had a CVC placed during operation.

Nutritional regimens were designed to be isocaloric and isonitrogenous over 1 week, and to deliver, for an average individual with a weight of 70 kg, 1.4 aminoacid/kg/day and 112 kJ/kg/day.

Enteral nutrition was based on a standard formula, with a kJ to mL ratio of 5 to 1 and glucose to lipid ratio of 70 to 30. The diet was infused continuously over 24 h with a peristaltic pump with controlled flow rate.
Until dischargeMean duration of artificial nutrition (SD, range)ETF : n=159
PN : n=158
ETF : 8.4 days (2.5, 3–21)
PN: 9.6 days (4.3, 7– 39)
Multicentre trial: 10 institutions.

34 patients (21%) in the ETF group were unable to tolerate the schedule infusion; 20 had a reduced enteral intake (mean 5292 kJ/day, SD 1462, range 3108–6972) and 14 (9%) switched to

PN. (Intention to treat analysis). No patient switched from PN to ETF.
Major complicationsETF: 20 (13%)
PN: 30 (19%)
Minor complicationsETF: 60 (38%)
Total number of complicationsPN: 88 (56%)

ETF: 80 (50%)
PN: 118 (75%)
Patients with postoperative complicationsMinor complications:
ETF: 40 (25%)
PN: 57 (36%)
RR (95% CI): 0.70 (0.50–0.98)
p= 0.035

Major complications:
ETF: 14 (9%)
PN: 21 (13%)
RR (95% CI): 0.66 (0.35–1.24)
p= 0.207

Total:
ETF: 54 (34%)
PN: 78 (49%)
RR (95% CI): 0.69 (0.53–0.90)
p=0.005

Infectious complications :
ETF : 25 (16%)
PN : 42 (27%)
RR (95% CI) : 0.59 (0.38– 0.92)
p= 0.018

Non-infectious complications :
ETF : 42 (26%)
PN : 57 (36%)
RR (95% CI) : 0.73 (0.52–1.02)
p=0.064
Mean duration of complications (SD, range):ETF: 4.7 days (2.3, 1– 14)

PN : 6.8 (4.2, 2–21)
Patients transferred to ICU:ETF: n=8
PN: n= 12

Mean LOS in ICU (n=20):

ETF : 5.7 days (SD 2.9, range 2–12)
PN : 10.4 days (SD 4.5, 2–18)
MortalityETF : n= 2 (1.3%)
PN : n= 5 (3.2%)
Mean LOS (Hospital)ETF : 13.4 days (4.1, 7– 39)
PN : 15.0 (5.6, 7–42)
p=0.009
Adverse effects of artificial nutrition:Abdominal distension :
ETF : 23 (14%)
PN : 10 (6%)
RR (95% CI) : 2.29 (1.15–4.60)
p= 0.018

Abdominal carmps :
ETF : 21 (13%)
PN : 8 (5%)
RR (95% CI) : 2.51 (1.22 –5.63)
p= 0.012

Diarrhoea :
ETF : 13 (8%)
PN : 9 (6%)
RR (95% CI) : 1.41 (0.65–3.20)
p=0.385

Vomiting :
ETF : 4 (3%)

PN : 3 (2%)
RR (95% CI) : 1.33 (0.34–5.22)
p= 0.709

Any adverse effect :
ETF : 56 (35%)
PN : 22 (14%)
RR (95% CI) : 2.53 (1.64–3.94)
p<0.0001
Mean (SD) distress scores (patients responded by scoring their distress from zero (very bad) to five (very well)Day 1 :
ETF : 1.8 (1.2)
PN : 2.0 (1.0)

Day 2 :
ETF : 2.2 (1.2)
PN : 2.4 (1.0)

Day 3 :
ETF : 2.7 (1.1)
PN : 2.9 (0.8)

Day 4 :
ETF : 3.2 (1.0)
PN : 3.1 (1.1 )

Day 5 :
ETF : 3.5 (0.9)
PN : 3.5 (0.8)

Day 6 :
ETF : 3.8 (0.9)
PN : 3.7 (0.8)

Day 7 :
ETF : 4.1 (0.8)
PN : 3.8 (0.9)
Braga et al 200143RCT1+257 patients

ETF: n= 126

PN: n= 131
Patients with cancer of the upper GI tract suitable for curative surgery.

Mean +/− SD age:
ETF: 64.1 +/− 13.1
PN: 62.9 +/− 12.4

Gender (M/F):
ETF: 68/58
PN: 71/60

Body weight (kg):
ETF: 65.9 +/− 13.7
PN: 66.8 +/− 14.9

Malnourished patients: n (%) (patients who had experienced an involuntary weight loss> 10% with respect to their usual body weight in the preceding 6 months were defined as malnourished):
ETF: 43 (34.1)
PN: 48 (36.6)

Karnofsky score:
ETF: 75 +/− 12
PN: 76 +/− 13

Exclusion criteria: renal (creatinine level > 30 mg/dL, hemodialysis), hepatic (ascites, portal hypertension, encephalopathy), cardiac (New York Heart Association class >3), or pulmonary dysfunction (arterial PaO2 of < 70 torr [9.3 kPa]), ongoing infection, neoadjuvant radiochemotherapy, and immune disorders (neutrophil level of < 2.0 x 109/L, hypoimmunoglobuline mia).
TPN started on POD 1 by giving 50% of the nutritional goal and from POD 2, patients received full regimen.

Nutritional goal: 25 kcal/kg/day.

Artificial nutrition was continued until patients achieved as adequate oral food intake (800 kcal/day).

Composition (per 100 mL):

Proteins (g): 4.0
Carbohydrates (g): 12.7
Lipids (g):5.0
Total calories (kcal): 110
+ vit and minerals
ETF through either jejunostomy or nasojejunal tube.

ETF starting 6 hours after the end of operation at a 10 mL/hr with a progressive increase to reach the full regimen on POD 4.

Nutritional goal: 25 kcal/kg/day.

Artificial nutrition was continued until patients achieved as adequate oral food intake (800 kcal/day).

Composition (per 100 mL):

Proteins (g): 4.1
Carbohydrates (g): 14.2
Lipids (g): 3.5
Total calories (kcal): 115
+ vit and minerals
Until dischargeMean (+/− SD) duration of artificial nutrition (days):ETF :n= 126
PN : n= 131

ETF : 12.8 +/− 5.5
PN : 13.2 +/− 4.9
In 8 patients (6.3%), a permanent stop of the infusion of enteral diet was necessary because of jejunostomy or NJ tube dislocation (n=5), emesis (n=2), and aspiration (n=5). These patients were switched to TPN but for outcome evaluation were considered in ETF group on an intent-to- treat basis.
Mean (SD, range) energy (kcal) intake per day in first post- op week:ETF : 1522 +/− 317 (564–2420)
PN : 1632 +/− 281 (855– 2518)
[p=0.11]
N patients achieve nutritional goal within 4 days postop:ETF : 100/126 (79.3%)
PN : 128/131 (97.7 %)
[p<0.001]
Percentage of patients experienced abdominal cramps:ETF : 14.2 %
PN : 4.5 %
Percentage of patients experienced abdominal distention:ETF : 12.6%
PN : 5.3%
Percentage of patients experienced diarrhoea:ETF : 11.1 % PN : 3.8%
Time to first flatus (days) (mean +/− SD):ETF : 2.4 +/− 1.3
PN : 4.6 +/− 2.0
[p= 0.003]
Time to first bowel movement (days) (mean +/− SD):ETF : 4.2 +/− 1.6
PN : 6.3 +/− 2.1
[p= 0.001]
Patients with infectious complications (%):ETF : 25 (19.8)
PN : 30 (22.9)
[Not significant]
Patients with non- infectious complications (%):ETF : 20 (15.8) PN : 23 (17.5)
[Not significant]
Overall patients with any complications (%):ETF : 45 (35.6)
PN : 53 (40.4) [Not significant]
Patients with major complications (%)(defined as the need of repeat laparotomy, percutaneous drainage of intra- abdominal deep fluid collection by interventional radiology procedures, or complications requiring patient transfer to the ICU).Total :
ETF : 16 (12.6)
PN : 21 (16)

- Repeat operation :
ETF : 8 (6.3)
PN : 10 (7.6)

- ICU transfer :
ETF : 4 (3.1)
PN : 5 (3.8)

- Interventional radiology :
ETF : 4 (3.1)
PN : 6 (4.5)
Death (%):ETF : 3 (2.3)
PN : 4 (3.0)
[Not significant]
Sepsis score (mean +/− SD):ETF : 8.5 +/− 3.5
PN : 10.4 +/− 3.7
[Not significant]
LOS (days) (mean +/− SD):ETF : 19.9 +/− 8.2
PN : 20.7 +/− 8.8
[Not significant]
Infectious complications:ETF : 27
PN : 36
- Abdominal abscess:ETF : 9
PN : 11
- Wound infections:ETF : 6
PN : 8
- Infected pancreatic or biliary fistula:ETF : 4
PN : 5
- Pneumonia:ETF : 3
PN : 6
- Urinary tract infection:ETF : 4
PN : 4
- Sepsis:ETF : 1
PN : 2
Noninfectious complications:ETF : 35
PN : 38
- Anastomotic leak:ETF : 9
PN : 11
- Delayed gastric emptying:ETF : 7
PN : 9
- Sterile pancreatic fistula:ETF : 7
PN : 8
- HemoperitoneumETF : 5
PN : 4
- GI bleedingETF : 3
PN : 3
- Respiratory failure:ETF : 2
PN : 2
- Cardiac failure:ETF : 2
PN : 1
Overall (infectious and non-infectious)ETF : 62
PN : 74
Outcomes in the subgroup of malnourished patients (n=91):ETF : n=43 ; PN : n=48
- Patients with infectious complications (%):ETF : 6 (13.9)
PN : 12 (25.0)
[p= 0.33]
- Patients with noninfectious complications (%):ETF : 10 (23.2) PN : 13 (27.0)
- Overall patients with any complication (%):ETF : 16 (37.1)
PN : 25 (52.0)
[p= 0.23]
- Patients with major complications (%):ETF : 9 (20.9)
PN : 12 (25.0)
- Repeat operation:ETF : 4 (9.3)
PN : 5 (10.4)
- ICU transfer:ETF : 3 (6.9)
PN : 3 (6.2)
- Interventional radiology:ETF : 2 (4.6)
PN : 4 (8.3)
Death (%):ETF : 1 (2.3)
PN : 2 (4.1)
Sepsis score (mean +/− SD):ETF : 9.2 +/− 3.6
PN : 11.3 +/− 3.3
LOS (days) (mean +/− SD):ETF : 19.8 +/− 8.9
PN : 22.6 +/− 9.7
[p=0.042]

ETF : n= 20 ; PN : n= 20
CD4/CD8 ratio (normal value, >1):Baseline :
ETF : 2.0 +/− 1.2
PN : 2.1 +/− 1.3

POD 1 :
ETF : 1.6 +/− 1.5
PN : 1.6 +/− 1.4

POD 8 :
ETF : 1.8 +/− 1.3
PN : 1.9 +/− 1.6
Plasma levels of albumin, prealbumin, Retinol-binding protein, C-reactive protein, IL-6, PMN, IL-2, total lymphocytes

Data not extracted (at any time point, no significant differences were found between the two groups in all the nutritional variables, immune function variables, and inflammatory response indices).
Delayed hypersensitivity response (performed in 40 consecutive patients 20 per group, using seven recall antigens according to the procedure suggested by the manufacturer- Multitest, Pasteur Merieux, Lyon, France).
Data not extracted.
Iovinelli et al165RCT48 patients

Intervention (TPN): n=24
Age:60.2±15
M/F:22/2

Comparison (ETF): n=24
Age:58.3±12
M/F:21/3
Patients undergoing total laryngectomy

Severely malnourished patients were excluded
Parenteral nutrition (subclavian venous catheter)
From 24hrs post-op
Enteral nutrition (PEG)Length of hospital stayLength of hospital stay (days)
Intervention:34±11
Comparison:26±11 [p<0.05]
PEG complications were clinically less significant than those associated with TPN Most common ETF complication was diarrhoea.

Most common PN complication was catheter related. The most serious being sepsis.

There was mild worsening of the nutritional status for both groups in approximately the first 10days post-op and a subsequent return toward pre-op values in the following days.
Wound infectionWound infection
Intervention:3
Comparison:3 [no diff]
Surgical complicationsSurgical complications (pharyngocutaneous fistulas)
Intervention:2
Comparison:1 [no diff]
Lim et al 1981208RCT24 patients

Intervention (TPN): n=12
Age:63.7
M/F:10/2

Comparison (ETF): n=12
Age:64.3
M/F:9/3
Patients with total dysphagia due to carcinoma of the oesophagusTotal parenteral nutritionGastrostomy tube

Glucose and water were given via the tube after 12hrs. Half strength of the solution was given for the firsts 2 days to prevent diarrhoea
Mortality
Intervention: n=10
Comparison: n=10
Mortality
Intervention:1
Comparison:2 [no diff]
TPN was found to be superior in achieving an earlier positive nitrogen balance & greater weight gain during a 4 week period. However gastrostomy is still preferred as the safe, cheap and safe method.
Anastomic leakAnastomic leak
Intervention:1
Comparison:4 [no diff]
Wound infectionWound infection
Intervention:3
Comparison:5 [no diff]
Weight gainWeight gain TPN had a final gain of 6.3% at the end of 4weeks [p<0.05]
Nitrogen balance
Reynolds et al 1997292RCT1+67 patients

ETF: 33
PN: 34
Patients undergoing major upper GI surgery for esophageal, gastric, or pancreatic malignancy.

Age (median- interquartile ranges):

ETF: 69 (51–81)
PN: 67 (25–86)

Gender (M/F):

ETF: 26/7
PN: 27/7
Subjective global assessment:

Well-nourished:
ETF: 6
PN: 7

Mildly malnourished:

ETF: 16
PN: 20

Severely malnourished:

ETF: 11
PN: 7

Preoperative jaundiced:

ETF: 1
PN: 4

Exclusion criteria: administration of steroids or immunosuppressive medication, abnormal renal function (serum creatinine > 1.5 mg/dL); preoperative evidence of bacteraemia; preoperative radiation therapy; history of intestinal disease precluding enteral feeding; preoperative TPN
TPN CVC. Standard parenteral formula: 2500 mL providing 9.4 g nitrogen and 1800 nonprotein kcal/24 h. Lipid constituted 55% of the nonprotein calories.

Feeding initiated at 9.00 am on the first pos op. day.

All patients were continued on their nutritional regimen for seven days. No attempt was made to enforce an isocaloric, isonitrogenous intake.
ETF via jejunostomy.

Osmolite providing 12.8 g nitrogen and 1680 nonprotein kcal (31% lipid) in 2000 mL per 24 hours once stabilised.

Introduced at 30 mL/h and the rate increased incrementally, depending on tolerance, up to 100 mL/h. The regimen was based on four 5- hourly feeds with a 1-hour rest period between each.

Feeding initiated at 9.00 am on the first pos op. day.

All patients were continued on their nutritional regimen for seven days. No attempt was made to enforce an isocaloric, isonitrogenous intake.
30 daysETF: n= 33; PN: n= 34No attempt was made to enforce an isocaloric, isonitrogenous intake.

30 patients from this study (15 from each group) were also randomised for a second study to assess gut permeability. Results from this second study have not been extracted. These 30 patients had a needle catheter jejunostomy inserted to enable comparative postoperative permeability studies to be performed in both groups.
Mean (SEM) Caloric intake (kcal/d) for the first 7 daysETF : 1300 +/− 300
PN : 1800 +/− 100 [Not significant]
Mean (SEM) nitrogen intake (g) for the first 7 daysETF : 8 +/− 3
PN : 10 +/− 1 [Not significant]
Intra- abdominal/thoracic abscessETF : 3
PN : 7 [p=0.3]
Major complications:
Pneumonia

ETF : 6
PN : 9 [p=0.2]
Pneumonia or abscessETF : 9
PN : 16 [p=0.1]
Central line sepsisETF : 1
PN : 3 [p=0.2]
Total infection episodesETF : 13
PN : 20 [p=0.2]
Infection episodes per patientETF : 0.4
PN : 0.5 [p=0.8]
Infections per infected patientsETF : 1.2
PN : 1.1 [p=0.8]
Noninfective complications:
DiarrhoeaETF : 5
PN : 1 [p=0.2]
Anastomotic leakETF : 1
PN : 1 [p=0.4]
Organ failureETF : 4
PN : 3 [p=0.9]
HemorrhageETF : 1
PN : 0 [p=0.9]
Bowel necrosisETF : 2
PN : 0 [p=0.4]
Cardiac complicationETF : 2
PN : 2 [p=0.6]
ThromboembolismETF : 1
PN : 0 [p=0.9]
MortalityETF : 2
PN : 1 [p=0.6]
Number of patients with complicationsETF : 13
PN : 17 [p=0.3]
Sand et al 1997303RCT29

Intervention: n=16

Comparison: n=13
Patients undergoing curative total gastrectomy for gastric cancerTotal parenteral nutritionEnteral nutrition by nasojejunal tubeInfective complicationsInfective complications
Intervention: 5
Comparison:3 [Not significant]
Parenteral nutrition was four times more expensive than Enteral nutrition

Pre-op nutrition not used
DiarrhoeaDiarrhoea began
Intervention: 3–5days
Comparison:5–7days
But there was a tendency to an increased risk of diarrhoea in the TPN group (Intervention)
MortalityMortality
Intervention: 1
Comparison: 0 (on day 45 from complications of oesophageal leakage)
Post-op complicationsPost-op complications
Intervention: 8
Comparison:5 [Not significant]
Serum CRP concentration
von Meyenfeldt et al 1992366RCT100 (only 2 groups of interest)

Intervention: n=51
Age:67.3±10.2
M/F:29/22

Comparison: n=50
Age:65.7±9.3
M/F:32/18
Patients with newly detected histological proven gastric or colorectal carcinoma requiring surgical treatment.Total parenteral nutritionEnteral nutrition10daysMortalityMortality
Intervention: 2
Comparison: 4
ETF was given either by NG tube or by mouth.

The presence of
depletion was defined using albumin, total lymphocyte counts & % ideal body weight – but the depleted & non depleted group not reported in this appraisal.

It is difficult to say if the same people suffer from more than one complication.

There were 4 groups in the study P values not provided for direct comparison for TPN v ETF.
Intra-abdominal abscessIntra-abdominal abscess
Intervention: 4
Comparison: 4
SepsisSepsis
Intervention: 1
Comparison :1
Sepsis related mortalitySepsis related mortality
Intervention: 1
Comparison: 2
Wound infectionWound infection
Intervention: 8
Comparison: 7
Wound dehiscenceWound dehiscence
Intervention: 2
Comparison: 1
Anastomotic leakageAnastomotic leakage
Intervention: 5
Comparison: 4
Complication rate of septic complications in patients with percentage weight loss over 10% of body weight
PN group: n=18
ETF group: n=13
Intra-abdominal abscess
Intervention: 0
Comparison: 2 [p<0.05]
Length of hospital stayLength of hospital stay
Intervention: 36.3±17.7
Comparison: 33.3±20.2
Zhu et al 2003383RCT1+40 Patients

ETF: n=20
PN: n=20
Patients were admitted for:

Total gastrectomy:
ETF: 6/20
PN: 8/20

Radical gastrectomy for cancer:
ETF: 12/20
PN: 11/20

Resection of esophageal carcinoma:
ETF: 2/20
PN: 1/20

Sex (M:F):
ETF: 12:8
PN: 10:10
ETF: The nasal tube was kept to superior jejunum. Patients were given 250ml rice water 24hrs after operation & nutrition through infusion pump. ETF was given continuously for 7daysPN: Patients given liquid of double power through central venous & peripheral venous. PN was given continuously for 7days7 daysTime of hospitalisation (days):ETF: 25 ± 8
TPN: 28 ± 8 [P>0.05]
Not significant
Incidence rate of diarrhoea:ETF: 15%
PN: Not reported

From: Appendix Four, Evidence Tables

Cover of Nutrition Support for Adults
Nutrition Support for Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition.
NICE Clinical Guidelines, No. 32.
National Collaborating Centre for Acute Care (UK).
Copyright © 2006, National Collaborating Centre for Acute Care.

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