Route of Nutritional Support for Pancreatic Fistula

October 4, 2016 updated by: National Taiwan University Hospital

Nutrition Through Oral Intake Versus Feeding Jejunostomy in the Conservative Treatment of Pancreatic Fistula After Pancreaticoduodenectomy: a Prospective Multicenter Randomized Clinical Trial

The aim of this study is to compare the closure rate of pancreatic fistula (PF) after pancreaticoduodenectomy (PD) under various types of nutrition.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 10002
        • Recruiting
        • National Taiwan University Hospital
        • Principal Investigator:
          • Yu-Wen Tien
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • aged more than 20 years old and develop pancreatic fistula after pancreatectomy

Exclusion Criteria:

  • major co-morbidities
  • severe pancreatic fistula needing intervention

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: oral intake
The patients at this arm were allowed to take food through mouth
Other: Jejunostomy tube feeding
The patients at this arm receive the nutritional support through the feeding jejunostomy tube; they can only eat or sip water through mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Closure of pancreatic fistula within 30 days
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Cost of therapy
Time Frame: 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Yu-Wen Tien, National Taiwan University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

December 18, 2012

First Submitted That Met QC Criteria

December 18, 2012

First Posted (Estimate)

December 24, 2012

Study Record Updates

Last Update Posted (Estimate)

October 5, 2016

Last Update Submitted That Met QC Criteria

October 4, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201202048RIB

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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