Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT01755260 |
| Other study ID # |
201202048RIB |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
December 18, 2012 |
| Last updated |
October 4, 2016 |
| Start date |
September 2013 |
Study information
| Verified date |
October 2016 |
| Source |
National Taiwan University Hospital |
| Contact |
Jin-Ming Wu, MD |
| Email |
kptkptkpt[@]yahoo.com.tw |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this study is to compare the closure rate of pancreatic fistula (PF) after
pancreaticoduodenectomy (PD) under various types of nutrition.
Description:
Postoperative pancreatic fistula (POPF) is the most detrimental complication of pancreatic
surgery due to the potential life-threatening consequences of fluid and electrolyte
imbalance, nutritional depletion, sepsis, and local complications, such as abdominal abscess
and hemorrhage.1 Incidence rates vary considerably from 0 to 24% due to the differences in
definitions with an overall rate of 12.9% in a recent series.1,2 Several risk factors have
been identified, mostly a soft parenchyma and a small main pancreatic duct diameter; however,
numerous attempts to reduce fistula rates with either pharmacological prophylaxis or
application of some special surgical techniques failed to improve postoperative outcomes. The
primary therapy for POPF today includes adequate drainage of pancreatic exocrine secretions
and conservative treatment, consisting of nutritional support and correction of electrolyte
disturbances and fistula-related complications. 3-5 These recommendations are based on
previous observations suggesting that up to 70% of cases eventually resolve
spontaneously.3,5,6 However, the patient's discomfort, the need for follow-up visits and the
substantial costs of prolonged therapy initiated various attempts to accelerate closure
rates. Several measures have been proposed, including fibrin glues, endoscopic interventions,
or the use of somatostatin analogues to inhibit pancreatic exocrine secretion. Nevertheless,
these methods lack any convincing evidence that the proposed regimens may be clinically
effective.4,7,8 Nutritional support is the key element of conservative therapy in patients
with POPF, as most of them are in a catabolic state and attempts to accelerate fistula
closure usually involve prolonged fasting. However, the decision between total parenteral
nutrition (TPN) and enteral nutrition is essentially arbitrary because the effects of both
diets on closure rates of postoperative pancreatic fistula have not been compared in a
randomized clinical trial.3,9 Experiments with healthy individuals have demonstrated that
intravenous feeding does not stimulate pancreatic secretion, and thus is a reasonable
solution when prolonged nutritional support is needed without increasing the exocrine
pancreatic function.10 However, previous research has suggested that long-term TPN leads to
negative functional and morphological changes, not only within the gastrointestinal mucosa
but also atrophy and dysfunction of the exocrine pancreas.11 Therefore, enteral feeding
beyond the ligament of Treitz is commonly preferred over the intravenous route due to lower
costs and the potential advantage of avoiding infectious and metabolic complications related
to the parenteral route. This hypothesis was substantiated in several clinical trials
demonstrating that enteral nutrition via a nasojejunal tube can be safely used in patients
with various disorders, including acute pancreatitis and postoperative pancreatic fistula.
12-15Some of these reports suggested that the enteral route offers major advantages over TPN
in terms of faster recovery and lower rates of disease- and nutrition-related
complications.16 However, data concerning chronic pancreatic conditions are limited.17 It is
well established that the duodenum is the major site of pancreatic secretion stimulation.
Cholecystokinin (CCK) and secretin released in the duodenum and enteropancreatic reflexes
mediated by vago-vagal cholinergic pathways are responsible for the majority of pancreatic
exocrine secretion.18Without raising CCK levels, the enteropancreatic reflex can be activated
with a corresponding increase in pancreatic enzyme secretion, by distention or administration
of hyperosmolar solutions in the duodenum. Pancreatic polypeptide (PP) secretion is also
under cholinergic control and thus may be a modulator of pancreatic secretion stimulated by
the vagal cholinergic pathway.19 It has also been shown that intraileal or colonic perfusion
of nutrients decreases pancreatic exocrine secretion, possibly mediated through the
ileal-brake gut peptides, namely peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). 20-22
Enteral feeding via a nasojejunal feeding tube necessitates endoscopic placement which could
be dangerous in immediately operated patients with gastrojejunostomy and might cause
tube-related discomfort to patients. Anatomically, pancreaticoduodenectomy will include
removal of duodenum and proximal 10 ~ 15 cm jejunum (Figure 1). In addition, another 30~40
cm-long jejunum will be brought up for pancreatic and biliary anastomosis (figure 2).
Therefore, the last enteral anastomosis (gastrojejunostomy or duodenojejunostomy) will be
made at site of 40~50 cm distal to Treitz ligament which is far more distal than site of
nasojejunal tube used in patients with acute pancreatitis. Therefore, we hypothesize that
oral feeding in patients operated with PD will not stimulate but inhibit pancreatic secretion
and hasten closure of pancreatic fistula. To test this hypothesis, we propose a prospective
randomized trial to test the effect of various nutrition methods on healing of PF after PD.
Patients will be randomized into 2 groups (A and B). Eligible patients will be randomized in
a 1:1 ratio to receive oral feeding nutrition, or TPN as a standard therapy of POPF. The
primary end points will be closure rate of PF. Secondary end points will include length and
cost of hospital stay after operation.
pancreatic exocrine secretion. Nevertheless, these methods lack any convincing evidence that
the proposed regimens may be clinically effective.
Nutritional support is the key element of conservative therapy in patients with POPF, as most
of them are in a catabolic state and attempts to accelerate fistula closure usually involve
prolonged fasting. However, the decision between total parenteral nutrition (TPN) and enteral
nutrition is essentially arbitrary because the effects of both diets on closure rates of
postoperative pancreatic fistula have not been compared in a randomized clinical trial.
Experiments with healthy individuals have demonstrated that intravenous feeding does not
stimulate pancreatic secretion, and thus is a reasonable solution when prolonged nutritional
support is needed without increasing the exocrine pancreatic function. However, previous
research has suggested that long-term TPN leads to negative functional and morphological
changes, not only within the gastrointestinal mucosa but also atrophy and dysfunction of the
exocrine pancreas. Therefore, enteral feeding beyond the ligament of Treitz is commonly
preferred over the intravenous route due to lower costs and the potential advantage of
avoiding infectious and metabolic complications related to the parenteral route. This
hypothesis was substantiated in several clinical trials demonstrating that enteral nutrition
via a nasojejunal tube can be safely used in patients with various disorders, including acute
pancreatitis and postoperative pancreatic fistula. Some of these reports suggested that the
enteral route offers major advantages over TPN in terms of faster recovery and lower rates of
disease- and nutrition-related complications. However, data concerning chronic pancreatic
conditions are limited.
It is well established that the duodenum is the major site of pancreatic secretion
stimulation. Cholecystokinin (CCK) and secretin released in the duodenum and enteropancreatic
reflexes mediated by vago-vagal cholinergic pathways are responsible for the majority of
pancreatic exocrine secretion. Without raising CCK levels, the enteropancreatic reflex can be
activated with a corresponding increase in pancreatic enzyme secretion, by distention or
administration of hyperosmolar solutions in the duodenum. Pancreatic polypeptide (PP)
secretion is also under cholinergic control and thus may be a modulator of pancreatic
secretion stimulated by the vagal cholinergic pathway. It has also been shown that intraileal
or colonic perfusion of nutrients decreases pancreatic exocrine secretion, possibly mediated
through the ileal-brake gut peptides, namely peptide YY (PYY) and glucagon-like peptide-1
(GLP-1).
Enteral feeding via a nasojejunal feeding tube necessitates endoscopic placement which could
be dangerous in immediately operated patients with gastrojejunostomy and might cause
tube-related discomfort to patients. Anatomically, pancreaticoduodenectomy will include
removal of duodenum and proximal 10 ~ 15 cm jejunum (Figure 1). In addition, another 30~40
cm-long jejunum will be brought up for pancreatic and biliary anastomosis (figure 2).
Therefore, the last enteral anastomosis (gastrojejunostomy or duodenojejunostomy) will be
made at site of 40~50 cm distal to Treitz ligament which is far more distal than site of
nasojejunal tube used in patients with acute pancreatitis. Therefore, we hypothesize that
oral feeding in patients operated with PD will not stimulate but inhibit pancreatic secretion
and hasten closure of pancreatic fistula. To test this hypothesis, we propose a prospective
randomized trial to test the effect of various nutrition methods on healing of PF after PD.
Patients will be randomized into 2 groups (A and B). Eligible patients will be randomized in
a 1:1 ratio to receive oral feeding nutrition, or TPN as a standard therapy of POPF. The
primary end points will be closure rate of PF. Secondary end points will include length and
cost of hospital stay after operation.
