Non-operative versus operative treatment for blunt pancreatic trauma in children.

Non-operative versus operative treatment for blunt pancreatic trauma in children (Review) Haugaard MV, Wettergren A, Hillingsø JG, Gluud C, Penninga L

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2014, Issue 2 http://www.thecochranelibrary.com

Non-operative versus operative treatment for blunt pancreatic trauma in children (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . ADDITIONAL TABLES . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW

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[Intervention Review]

Non-operative versus operative treatment for blunt pancreatic trauma in children Michael V Haugaard1 , André Wettergren2 , Jens Georg Hillingsø1 , Christian Gluud3 , Luit Penninga4 1 Department

of Surgery and Transplantation C2122, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Klinik Hvidovre, Hvidovre, Denmark. 3 The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4 Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 2 Kirurgisk

Contact address: Michael V Haugaard, Department of Surgery and Transplantation C2122, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100 Ø, Denmark. [email protected]. Editorial group: Cochrane Injuries Group. Publication status and date: New, published in Issue 2, 2014. Review content assessed as up-to-date: 21 June 2013. Citation: Haugaard MV, Wettergren A, Hillingsø JG, Gluud C, Penninga L. Non-operative versus operative treatment for blunt pancreatic trauma in children. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD009746. DOI: 10.1002/14651858.CD009746.pub2. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Pancreatic trauma in children is a serious condition with high morbidity. Blunt traumatic pancreatic lesions in children can be treated non-operatively or operatively. For less severe, grade I and II, blunt pancreatic trauma a non-operative or conservative approach is usually employed. Currently, the optimal treatment, of whether to perform operative or non-operative treatment of severe, grade III to V, blunt pancreatic injury in children is unclear. Objectives To assess the benefits and harms of operative versus non-operative treatment of blunt pancreatic trauma in children. Search methods We searched the Cochrane Injuries Group’s Specialised Register, Cochrane Central Register of Controlled Trials (Issue 5, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED and CPCI-S) and ZETOC. In addition, we searched bibliographies of relevant articles, conference proceeding abstracts and clinical trials registries. We conducted the search on the 21 June 2013. Selection criteria We planned to select all randomised clinical trials investigating non-operative versus operative treatment of blunt pancreatic trauma in children, irrespective of blinding, publication status or language of publication. Data collection and analysis We used relevant search strategies to obtain the titles and abstracts of studies that were relevant for the review. Two review authors independently assessed trial eligibility. Non-operative versus operative treatment for blunt pancreatic trauma in children (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Main results The search found 83 relevant references. We excluded all of the references and found no randomised clinical trials investigating treatment of blunt pancreatic trauma in children. Authors’ conclusions This review shows that strategies regarding non-operative versus operative treatment of severe blunt pancreatic trauma in children are not based on randomised clinical trials. We recommend that multi-centre trials evaluating non-operative versus operative treatment of paediatric pancreatic trauma are conducted to establish firm evidence in this field of medicine.

PLAIN LANGUAGE SUMMARY Treatment of severe blunt pancreatic lesions in children Background Optimal treatment of severe blunt pancreatic trauma in children has long been debated, some doctors advocate operation while others prefer a conservative approach without operation as primary treatment. We conducted this systematic review to assess which strategy should be preferred. Blunt trauma to the pancreas typically occurs after crashes involving a bicycle handlebar, road traffic crashes or other types of injury that cause a blow to the upper abdomen. Study characteristics We searched medical databases for randomised (where two groups of children were randomly assigned to treatment or no treatment) clinical trials of children treated for blunt trauma to the pancreas by an operation or no operation. The children were aged 17 years or younger. The search was current to June 2013. Key results We found no randomised clinical trials investigating operative treatment compared with non-operative treatment of severe pancreatic injury in children, hence we have no firm evidence to support either operative treatment or non-operative treatment of severe pancreatic lesions in children. Although difficult because of the rarity and the acute nature of these lesions, we recommend that multicentre randomised clinical trials of good quality are conducted.

BACKGROUND

Description of the condition Pancreatic trauma in children is a serious condition that is associated with high morbidity (Kao 2003). Pancreatic pseudocyst formation, pancreatitis and pancreatic fistula formation are common complications of pancreatic trauma, and 19% to 55% of people experience pancreas-related complications after pancreatic trauma (Wales 2001; Stringer 2005; Haugaard 2012). Furthermore, morbidity, including pneumonia and pleural fluid collections, frequently occurs in people with traumatic lesions of the pancreas (Haugaard 2012). Mortality in people with pancreatic trauma is estimated to be 3% to 8% (Bosboom 2006; Haugaard

2012). Isolated pancreatic trauma is seldom lethal, but pancreatic trauma in children can be life threatening in association with other organ injuries, cranial injuries or injuries of major blood vessels in the peripancreatic area (Kao 2003). Trauma of the pancreas is divided into blunt and penetrating injuries. Blunt pancreatic trauma is by far the most common type of trauma mechanism in children, and it is typically seen after crashes involving a bicycle handlebar, road traffic crashes or other types of crashes that cause a blow to the upper abdomen (de Blaauw 2008). Penetrating injuries of the pancreas are much more seldom in children, and may be a result of gunshot or stabbing injuries (Akhrass 1997). Pancreatic trauma is the fourth most common type of internal organ trauma in children. It has been reported to occur in 3%


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to 12% of blunt injuries and in 1.1% of penetrating injuries in children (Juric 2009). Pancreatic injury is normally graded in five categories according to the organ injury scale of the American Association for the Surgery of Trauma (AAST), with pancreatic duct status being the most important factor (Moore 1990). These categories are summarised in Table 1. Diagnosing pancreatic trauma is difficult. The abdominal symptoms such as pain, nausea and vomiting are often unspecific, and are not correlated to the seriousness of the trauma (Bosboom 2006; Haugaard 2012). Serum amylase is increased in 55% to 91% of people with pancreatic lesions (Bass 1988; Graham 2000). Typically, serum amylase raises 2 to 12 hours after injury, and is elevated for up to two to five days after injury (Bass 1988). Grade III to IV pancreatic lesions have a higher initial and maximum amylase value when compared with grade I to II lesions (Haugaard 2012). Elevation of amylase beyond 10 to 30 days after trauma is associated with an increased risk of pseudocyst formation (Bass 1988; Bosboom 2006). Radiological investigations are important for the diagnosis of pancreatic trauma. Ultrasound examination is often performed in the emergency department and supplies information on free peritoneal fluid and co-existing damage of other organs such as the liver and spleen (Bosboom 2006). Due to its retroperitoneal localisation, the pancreas is usually difficult to visualise with ultrasound. Computer tomography (CT) is used to detect pancreatic damage; however, it is not always possible to detect pancreatic lesions when CT is performed shortly after the accident. Therefore, CT might be repeated after 24 hours when suspicion of pancreatic lesions persist (Bosboom 2006; Haugaard 2012). Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are considered valuable diagnostic tools for detecting pancreatic duct lesions (Hall 1986). MRCP is non-invasive, while ERCP is invasive and may cause iatrogenic pancreatitis (Bosboom 2006; Haugaard 2012). ERCP gives the possibility of immediate intervention of the pancreatic duct lesion by inserting a stent (Bosboom 2006; Houben 2007).

Description of the intervention Pancreatic trauma in children can be treated non-operatively or operatively (Paul 2011; Penninga 2011). The non-operative approach often consists of close monitoring of the child’s clinical condition; repeated radiological investigations such as CT, ultrasound and MRCP; monitoring of the child’s amylase and lipase levels and, optionally, parenteral nutrition (Haugaard 2012). In addition, ERCP with placement of a stent in the damaged pancreatic duct is used in some centres as part of the non-operative approach (Bosboom 2006; Houben 2007). Experience with placement of a stent using ERCP is very limited, and only described in very few cases (Houben 2007; Canty 2001). In adults a fracture of the pancreas involving the pancreatic duct or the common bile duct can be treated with a papillotomy in some cases (Jaik 2008).

Ultrasound-guided drainage of abdominal and peripancreatic fluid collections, and pancreatic pseudocysts, is frequently applied (Bass 1988; Wales 2001). The operative approach to pancreatic trauma can consist of laparotomy with drainage of the peripancreatic area, distal pancreatectomy with or without preservation of the spleen, Rouxen-Y pancreaticojejunostomy, and, more seldom, pancreaticoduodenectomy (Whipple’s procedure). The type of operation depends on the grade and localisation of the pancreatic lesion (Meier 2001). Spleen-preserving surgery should be attempted to avoid the lifelong increased risk of infections after splenectomy (Kertai 2010). In case of trauma where multiple organs are involved and an acute laparotomy is performed, the damage control resuscitation concept must be applied and the pancreatic resection done as part of a staged surgery in a center with extensive hepato-pancreato-biliary (HPB) experience (Seamon 2009; Sutton 2006). Grade I and II blunt pancreatic injuries in children are treated non-operatively. The optimal treatment of blunt AAST grade III and IV injuries is unclear (Mattix 2007). There might be a trend towards non-operative treatment of blunt severe paediatric pancreatic lesions (de Blaauw 2008). In adults, blunt grade III and IV pancreatic injuries are generally treated operatively. However, in adults the preference for operative treatment is not based on randomised trials. Differences in morbidity and hospital stay between operative and non-operative treatment have been reported for children with blunt pancreatic lesions (Meier 2001; Wales 2001; Haugaard 2012). Patients who initially are treated non-operatively might require an operation when the clinical condition of the patient worsens (Stringer 2005). When worsening of the clinical condition of the patient occurs, it is frequently due to infection or sepsis (Stringer 2005). It is currently unclear what consequences the delay of surgery has in patients where initially a non-operative approach has been chosen, but who eventually receive an operation due to worsening of the condition (Vane 2009). It has been suggested that surgery is technically more difficult in patients who initially have been treated non-operatively due to intraabdominal adhesions and leakage of pancreatic enzymes in the surgical field (Meier 2001).

Why it is important to do this review Pancreatic trauma in children is a serious condition. Currently, the optimal treatment of serious paediatric pancreatic injury (AAST grade III to V) is unclear (Penninga 2011). A Cochrane review is warranted to summarise the available evidence and the benefits and harms of non-operative versus operative treatment in children with serious blunt (AAST grade III to V) pancreatic injury. We have not been able to identify any existing systematic reviews evaluating the benefits and harms of non-operative versus operative treatment for serious pancreatic trauma in children or adults.


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OBJECTIVES

Search methods for identification of studies

To assess the benefits and harms of operative versus non-operative treatment of blunt pancreatic trauma in children.

We placed no restrictions on date, language or publication status.

Electronic searches

METHODS

Criteria for considering studies for this review

Types of studies We planned to include randomised clinical trials, irrespective of blinding, language and publication status.

Types of participants

The Cochrane Injuries Group Trials Search Co-ordinator searched the following: 1. Cochrane Injuries Group Specialised Register (21 June 2013); 2. Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5 of 12, 2013); 3. MEDLINE (OvidSP) (1946 to June week 2 2013); 4. Embase (OvidSP) (1974 to 20 June 2013); 5. ISI Web of Science: Science Citation Index Expanded (SCIEXPANDED) (1970 to June 2013); 6. ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to June 2013); 7. ZETOC (1993 to June 2013).

Children with blunt pancreatic trauma grade I to V, who were 17 years of age or younger. Searching other resources Types of interventions Operative treatment versus non-operative interventions or no intervention for pancreatic trauma.

Types of outcome measures

We searched bibliographies of relevant articles. We searched relevant conference proceeding abstracts and the following online trials registers through 5 December 2013: • Current Controlled Trials (www.controlled-trials.com); • Clinicaltrials.gov (www.clinicaltrials.gov); • The World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp).

All outcome measures were planned to be assessed at final followup.

Primary outcomes

1. Mortality. 2. Pancreatic complications (pancreatic pseudocysts, fistulas, pancreatitis, abscesses).

Data collection and analysis The Injuries Group’s Trials Search Co-ordinator performed the electronic database searches. She collated results using bibliographic software and then forwarded titles and abstracts to the review authors for screening. The review authors carried out searches of all other resources.

Secondary outcomes

1. Other complications (infections, wound problems). 2. Diabetes mellitus. 3. Other adverse events. Serious complications/adverse events were defined as any untoward medical occurrence that was life threatening; resulted in death, or persistent or significant disability; or any medical event that might have jeopardised the child, or required further intervention to prevent harm (ICH-GCP 1996). 4. Hospital length of stay among children who survived until hospital discharge.

Selection of studies Two review authors (MH and LP) independently assessed the search results for study eligibility. We obtained full-text copies of all studies that met the inclusion criteria. We listed studies that were subsequently excluded in the review with the reason for exclusion (Characteristics of excluded studies). We solved disagreements by discussion or in consultation with a third review author (CG). We had planned to contact the authors of the trials if information about methodology or data was unclear or missing.


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Data extraction and management Two review authors (MH and LP) planned to independently extract data using standard data extraction forms (Moher 2009; Higgins 2011). We were to translate studies reported in non-English language journals before assessment. Where multiple publications from one study existed, we planned to group reports together and mark the publication with the most complete data as the primary reference. Where relevant outcomes were published in other reports, we planned to use these data. We would have resolved disagreements by consultation with all authors. From each trial, we were to extract the following information: first author, country of origin, study design, inclusion and exclusion criteria, number of participants, participant characteristics, injury severity, single- or multi-organ trauma, number of children treated operatively, number of children treated non-operatively, the intervention administered in the two treatment groups (e.g. type of operation, type of non-operative intervention), follow-up period, primary and secondary outcomes, adverse events and participants lost for follow-up. If information was not available in the published trial, we intended to contact authors of the publications in order to assess the trials correctly. We planned to use ’Summary of findings’ tables in which the primary outcome measures would be assessed. Assessment of risk of bias in included studies The design and reporting of a randomised clinical trial will restrict bias in the comparison of the intervention with the control (Moher 1998; Gluud 2006). According to empirical evidence (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008), we intended to assess the risk of bias in the included trials according to the following criteria: Sequence generation

• Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards and throwing dice are adequate if performed by an independent adjudicator. • Uncertain risk of bias: the trial was described as randomised, but the method of sequence generation was not specified. • High risk of bias: the sequence generation method was not, or may not be, random. Allocation concealment

• Low risk of bias: allocation was controlled by a central and independent randomisation unit, sequentially numbered, opaque and sealed envelopes or similar, so that intervention allocations could not have been foreseen in advance of, or during, enrolment. • Uncertain risk of bias: the trial was described as randomised but the method used to conceal the allocation was not described,

so that intervention allocations may have been foreseen in advance of, or during, enrolment. • High risk of bias: if the allocation sequence was known to the investigators who assigned participants. Blinding of participants and personnel

• Low risk of bias: the trial was described as blinded for participants and personnel, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial. • Uncertain risk of bias: the trial was described as blind for participants and personnel, but the method of blinding was not described. • High risk of bias, the trial was not blinded for participants and personnel, and so group allocation was known during the trial. Blinding of outcome assessment

• Low risk of bias: the trial was described as blinded for outcome assessors from knowledge of which intervention a participant received, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial. • Uncertain risk of bias: the trial was described as blinded for outcome assessors, but the method of blinding was not described. • High risk of bias, the trial was not blinded for outcome assessors, and so group allocation was known during the trial. Incomplete outcome data

• Low risk of bias: the numbers and reasons for dropouts and withdrawals in all intervention groups were described, or it was specified that there were no dropouts or withdrawals. • Uncertain risk of bias: the report gave the impression that there had been no dropouts or withdrawals, but the number and reasons were not specifically stated. • High risk of bias: the number and reasons for dropouts and withdrawals were not described. Selective outcome reporting

• Low risk of bias: predefined, or clinically relevant and reasonably expected outcomes were reported on. • Uncertain risk of bias: not all predefined, or clinically relevant and reasonably expected outcomes were reported on or were not reported fully, or it is unclear whether data on these outcomes were recorded or not. • High risk of bias: one or more predefined, clinically relevant, or other reasonably expected outcomes were not reported; data on these outcomes were likely to have been collected.


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Other biases

• Low risk of bias (the trial appeared to be free of other sources of bias; e.g. conflict of interest bias). • Uncertain risk of bias (there was insufficient information to assess whether other sources of bias were present). • High risk of bias (it is likely that potential sources of bias were related to specific design used, or other bias risks are present). Review authors’ judgements were planned to be based on the definitions of the above listed domains. Measures of treatment effect For dichotomous outcomes, results were planned to be expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the outcomes of treatment, we planned to use the mean difference (MD) or the standardised mean difference (SMD) if different scales were used (Thompson 2002). Dealing with missing data We intended to handle missing data as follows: • contact the investigators to request missing data; • perform sensitivity analyses to assess how sensitive our results are to reasonable changes in the assumptions that were made; • for incomplete data, to perform ’worst-worst’ case scenario analyses, ’best-best’ case scenario analyses, ’worst-best’ case scenario analyses, and ’best-worst’ case scenario analyses. Assessment of heterogeneity We planned to assess heterogeneity using a Chi2 test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance, and with the I2 test (Higgins 2003). Assessment of reporting biases We planned to use a funnel plot to explore bias, if there were at least 10 studies included in an analysis (Egger 1997; Macaskill 2001). Asymmetry in the funnel plot was to be used to assess this collective form of bias. We planned to perform linear regression to determine the funnel plot asymmetry (Egger 1997), if we had a minimum number of 10 trials. Data synthesis We planned to pool the data using both the random-effects and the fixed-effect models to ensure robustness of the result. In case of significant differences of the results from the two models, we planned to provide both results. If the difference in the results was

not significant, then we planned to present the results using the random-effects model (Higgins 2002), as heterogeneity might be expected between studies due to differences in preferred operation type, availability of non-operative procedures and type of surgeons performing the operations. Subgroup analysis and investigation of heterogeneity We planned subgroup analyses for the: 1. type of operation performed; 2. type of non-operative intervention performed; 3. grade of pancreatic lesion. We planned to perform a test of interaction to evaluate the differences between the estimates, using the method described in Section 9.6.3 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Sensitivity analysis 1. Trials with low risk of bias in the domain allocation concealment compared with trials with allocation concealment at high risk of bias; 2. to assess how sensitive our results are to reasonable changes in the assumptions that were made, as described in the Dealing with missing data section. Trial sequential analysis

We planned to apply trial sequential analysis as cumulative metaanalyses are at risk of producing random errors because of sparse data, and repetitive testing on accumulating data (Wetterslev 2008; Wetterslev 2009). To minimise random errors, we intended to calculate the required information size (i.e. the number of participants needed in a meta-analysis to detect or reject a certain intervention effect) (Wetterslev 2008). Information size calculation should also account for the diversity present in the meta-analysis. In our meta-analysis, we planned information size to be based on the assumption of a plausible relative risk reduction of 20% or on the relative risk reduction observed in the included trials with low risk of bias (Wetterslev 2008). The underlying assumption of trial sequential analysis is that significance testing may be performed each time a new trial is added to the meta-analysis. We planned to add the trials according to the year of publication and, if more than one trial was published in a year, we planned to add trials alphabetically according to the last name of the first author (TSA manual 2011). On the basis of the outcome proportion in the control group and the mentioned RRs, the risk for type I (5%) and type II (20%) errors, and the diversity, the required information size, and the trial sequential monitoring boundaries were planned to be constructed (Wetterslev 2008). These boundaries should determine the statistical inference one may draw regarding the cumulative meta-analysis that has not reached the required information size. If a trial sequential monitoring boundary is crossed before the


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required information size is reached in a cumulative meta-analysis, firm evidence may have been established and further trials may be superfluous. In contrast, if the boundaries are not surpassed, it is most probably necessary to continue doing trials in order to detect or reject a certain intervention effect. We had planned to use as default a type I error of 5%, type II error of 20%, and to adjust information size for diversity unless otherwise stated (Wetterslev 2008; Wetterslev 2009). We planned to perform analyses using trial sequential analysis software (TSA manual 2011).

RESULTS

Description of studies

Results of the search The search identified 442 references (Figure 1). After removal of duplicates, 396 references remained. After removal of 313 irrelevant references based on the title or abstract, or both, we retrieved the full-text of 83 articles reporting on paediatric pancreatic trauma. We decided to study all these 83 articles and their reference lists to get a complete overview of the topic, even though the title or abstract of the articles already reported that the type of study was not a randomised clinical trial. After reading all 83 articles, we excluded them all as there were no randomised clinical trials.


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Figure 1. Study flow diagram.


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Included studies We found no randomised clinical trials comparing non-operative versus operative treatment in children with pancreatic trauma.

Excluded studies We excluded all retrieved trials, as they were not randomised, or not relevant to the topic of this review.

Risk of bias in included studies We included no trials in this review.

Effects of interventions We included no trials in this review.

DISCUSSION Summary of main results There is currently no consensus whether blunt pancreatic lesions in children should be treated operatively or non-operatively. There is generally consensus that mild blunt pancreatic trauma without lesion of the pancreatic duct (grade I to II) should be treated non-operatively (Haugaard 2012). In contrast, treatment of severe blunt pancreatic trauma with lesion of the pancreatic duct (grade III to V) is controversial, and treatment can either be non-operative or operative.

Quality of the evidence We found no published or pending randomised clinical trials that compared non-operative versus operative treatment of pancreatic trauma in children for inclusion in this review. Therefore, all available evidence is based on non-randomised studies. We detected a number of non-randomised studies during the search that reported on non-operative and operative treatment in children with pancreatic lesions. Most of the studies were retrospective case series. We have summarised the results of these including complications seen in the different studies associated with both non-operative and operative treatment (Table 2; Table 3; Table 4). Proponents of operative surgical intervention argue that it reduces the risk of secondary complications, especially the formation of pancreatic pseudocysts and that delay in surgical intervention leads

to greater morbidity (Smith 1988; McGahren 1995; Meier 2001; Snajdauf 2007). Operative treatment can either be explorative laparotomy with drainage or more extensive surgery. If the distal part of the pancreatic duct is damaged, some surgeons advocate a spleen-sparing distal pancreatectomy (Jobst 1999; Kolar 2005). A spleen-removing distal pancreatectomy is performed in adults, but is avoided in children because of the increased risk of infections (Kertai 2010). In trauma involving the proximal pancreatic duct or the pancreatic head (or both), a Roux-en-Y pancreaticojejunostomy with preservation of the pancreatic tail is performed (Stringer 2005). If both the pancreatic head and duodenum are severely damaged, a radical pancreaticoduodenectomy, Whipple’s operation, can be performed (Meier 2001). In contrast, other doctors propose a non-operative approach, arguing to avoid surgery if possible and instead observe the patient closely, and to only perform an operation if the patient’s clinical condition deteriorates or the patient shows signs of haemodynamic instability (Kouchi 1999). As a part of the non-operative treatment, some centres keep the patient fasting, use total parenteral nutrition (TPN) and place a nasogastric tube with suction to alleviate pain and nausea (Alanen 2000). Moreover, these doctors argue that complications seen with non-operative treatment, such as formation of pancreatic pseudocysts, often are treated successfully by non-surgical treatment options such as ultrasound-guided percutaneous external drainage (PED) (Haller 1994; Shilyansky 1998; Lucaya 1998; Holland 1999; Wales 2001), or endoscopic ultrasound-guided drainage (EUS). Other studies recommend the insertion of a stent by ERCP in cases where the pancreatic duct is completely or partially lacerated thereby avoiding open surgical intervention (Rescorla 1995; Canty 2001). Experience with this procedure is limited, and there might be an increased risk of developing strictures of the pancreatic duct, besides the fact that the child has to undergo general anaesthesia (de Blaauw 2008). The non-randomised studies showed that mortality in children with blunt isolated pancreatic trauma is rare. When mortality occurs, it is associated with other complications such as multi-organ injury, injury of large blood vessels, severe head trauma and sepsis. Pancreas-related morbidity, especially formation of pancreatic pseudocysts, in patients treated non-operatively might be higher than in patients treated operatively. In contrast, morbidity outside the pancreas, such as sepsis, pleural effusion and formation of nonpancreatic abscesses, might be lower when undergoing non-operative treatment compared with operative treatment (Haugaard 2012). Long-term complications after both operative and nonoperative treatment occur seldomly, and chronic endocrine and exocrine dysfunction is rarely seen, even in patients with severe pancreatic lesions (Wales 2001). Penetrating pancreatic lesions are predominantly caused by gunshot wounds, and are associated with a high risk of multiple or-


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gan damage and injury of the large blood vessels in the abdominal and thoracic region. Therefore, all penetrating pancreatic lesions are generally treated surgically by an exploratory laparotomy (Firstenberg 1999). However, penetrating pancreatic lesions are not the focus of this review, and consensus exists that penetrating pancreatic lesions are treated surgically. Operative treatment in all patients with pancreatic trauma is generally indicated if the patient’s clinical status worsens, shows signs of peritoneal irritation or becomes haemodynamically unstable. Traumatic pancreatic lesions in children are rare, and the acute nature of the condition makes it difficult to conduct large randomised trials in this field of medicine. This review found no randomised trials despite searching all relevant databases. This makes it impossible to conclude anything definitive about whether operative or non-operative treatment should be applied in children with severe blunt pancreatic lesions (grade III to V), because such a conclusion would be associated with high risk of bias.

AUTHORS’ CONCLUSIONS Implications for practice This review showed that strategies regarding non-operative ver-

sus operative treatment of pancreatic trauma in children are not based on randomised trials. The decision to institute either nonoperative or operative treatment seems to be made out of general practice in any particular institution.

Implications for research Lack of randomised clinical trials might be due to the low incidence of blunt pancreatic lesions, the paediatric population and the acute nature of the condition. Performing a randomised clinical trial would be difficult, but not impossible. These trials should be multicentre trials, and should be performed with low risk of systematic error and with low risk of random error, and follow the CONSORT (Consolidated Standards of Reporting Trials) guidelines. Conduct of such multicentre trials evaluating non-operative versus operative treatment of blunt paediatric pancreatic trauma can establish firm evidence.

ACKNOWLEDGEMENTS We would like to thank Emma Sydenham, Karen Blackhall and Deirdre Beecher from the Cochrane Injuries Group for their support in preparing the protocol and the review.

REFERENCES

Additional references Akhrass 1997 Akhrass R, Yaffe MB, Brandt CP, Reigle M, Fallon WF Jr, Malangoni MA. Pancreatic trauma: a ten-year multiinstitutional experience. The American Surgeon 1997;63: 598–604. Alanen 2000 Alanen M, Pajulo O, Reunanen M. Pancreatic injuries in children. Annals Chirurgica Gynaecologica 2000;89(4): 277–80. Bass 1988 Bass J, Di Lorenzo M, Desjardins JG, Grignon A, Ouimet A. Blunt pancreatic injuries in children: the role of percutaneous external drainage in the treatment of pancreatic pseudocysts. Journal of Pediatric Surgery 1988;23 (8):721–4. Bass 1991 Bass DH, Lakhoo K. Pancreatic injuries in children. South African Journal of Surgery. Suid-Afrikaanse Tydskrif vir Chirurgie 1991;29(2):39–40. [PUBMED: 1882310] Bosboom 2006 Bosboom D, Braam AW, Blickman JG, Wijnen RM. The role of imaging studies in pancreatic injury due to blunt abdominal trauma in children. European Journal of Radiology 2006;59(1):3–7.

Canty 2001 Canty TG Sr, Weinman D. Management of major pancreatic duct injuries in children. Journal of Trauma 2001;50(6):1001–7. de Blaauw 2008 de Blaauw I, Winkelhorst JT, Rieu PN, van der Staak FH, Wijnen MH, Severijnen RS, et al.Pancreatic injury in children: good outcome of nonoperative treatment. Journal of Pediatric Surgery 2008;43:1640–3. Egger 1997 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34. Fabbro 2001 Fabbro MA, D’Agostino S, Romanini MV, Chiarenza F, Fasoli L, Musi L, et al.Management of severe blunt pancreatic trauma in children. Personal experience. La Pediatria Medica e Chirurgica: Medical and Surgical Pediatrics 2001;23(3-4):179–82. [PUBMED: 11723854] Firstenberg 1999 Firstenberg MS, Volsko TA, Sivit C, Stallion A, Dudgeon DL, Grisoni ER. Selective management of pediatric pancreatic injuries. Journal of Pediatric Surgery 1999;34(7): 1142–7.


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Gluud 2006 Gluud LL. Bias in clinical intervention research. American Journal of Epidemiology 2006;163(6):493–501. Gorenstein 1987 Gorenstein A, O’Halpin D, Wesson DE, Daneman A, Filler RM. Blunt injury to the pancreas in children: selective management based on ultrasound. Journal of Pediatric Surgery 1987;22(12):1110–6. [PUBMED: 3326925] Graham 2000 Graham CA, O’Toole SJ, Watson AJ, Munro FD, Haddock G. Pancreatic trauma in Scottish children. Journal of the Royal College of Surgeons Edinburgh 2000;45(4):223–6. Hall 1986 Hall RI, Lavelle MI, Venables CW. Use of ERCP to identify the site of traumatic injuries of the main pancreatic duct in children. British Journal of Surgery 1986;73(5):411–2. Haller 1994 Haller JA Jr, Papa P, Drugas G, Colombani P. Nonoperative management of solid organ injuries in children. Is it safe?. Annals of Surgery 1994;219(6):625–8. Haugaard 2012 Haugaard MV, Penninga L, Ifaoui IB, Qvist N, Wettergren A. Pancreatic trauma in children - operative versus nonoperative treatment. Ugeskrift for Laeger (Journal of the Danish Medical Association) 2012;174(3):115–9. Higgins 2002 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 2002;21(11):1539–58. Higgins 2003 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327: 557–60. Higgins 2011 Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Holland 1999 Holland AJ, Davey RB, Sparnon AL, Chapman M, LeQuesne GW. Traumatic pancreatitis: long-term review of initial non-operative management in children. Journal of Paediatric Child Health 1999;35(1):78–81. Houben 2007 Houben CH, de-Ajayi N, Patel S, Kane P, Karani J, Devlin J, et al.Traumatic pancreatic duct injury in children: minimally invasive approach to management. Journal of Pediatric Surgery 2007;42:629–35. ICH-GCP 1996 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Guideline for good clinical practice. E6 (R1), 1996. www.ich.org/products/guidelines/efficacy/ efficacy-single/article/good-clinical-practice.html (accessed 3 December 2013).

Jaik 2008 Jaik NP, Hoey BA, Stawicki SP. Evolving role of endoscopic retrograde cholangiopancreatography in management of extrahepatic hepatic ductal injuries due to blunt trauma: diagnostic and treatment algorithms. HPB surgery : a world journal of hepatic, pancreatic and biliary surgery 2008;2008: 259141. [PUBMED: 18475313] Jobst 1999 Jobst MA, Canty TG Sr, Lynch FP. Management of pancreatic injury in pediatric blunt abdominal trauma. Journal of Pediatric Surgery 1999;34(5):818–23. Juric 2009 Juric I, Pogorelic Z, Biocic M, Todoric D, Furlan D, Susnjar T. Management of blunt pancreatic trauma in children. Surgery Today 2009;39:115–9. Kao 2003 Kao LS, Bulger EM, Parks DL, Byrd GF, Jurkovich GJ. Predictors of morbidity after traumatic pancreatic injury. Journal of Trauma 2003;55:898–905. Keller 1997 Keller MS, Stafford PW, Vane DW. Conservative management of pancreatic trauma in children. The Journal of Trauma 1997;42(6):1097–100. [PUBMED: 9210548] Kertai 2010 Kertai MA, Boehner C, Maiss J, Huemmer HP, Reingruber B. Nonoperative management of the child with severe pancreatic and splenic injury: should this become our preferred approach?. Journal of Trauma 2010;68(2):E44–8. Kjaergard 2001 Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Annals of Internal Medicine 2001;135(11):982–9. Kolar 2005 Kolar I. One early and three delayed distal pancreatectomies without splenectomy and with preservation of the splenic vessels after traumatic transection of the distal pancreas in children. European Journal of Pediatric Surgery 2005;15(2): 132–6. Kouchi 1999 Kouchi K, Tanabe M, Yoshida H, Iwai J, Matsunaga T, Ohtsuka Y, et al.Nonoperative management of blunt pancreatic injury in childhood. Journal of Pediatric Surgery 1999;34(11):1736–9. Lucaya 1998 Lucaya J, Vazquez E, Caballero F, Chait PG, Daneman A, Wesson D. Non-operative management of traumatic pancreatic pseudocysts associated with pancreatic duct laceration in children. Pediatric Radiology 1998;28(1):5–8. Macaskill 2001 Macaskill P, Walter SD, Irwig L. A comparison of methods to detect publication bias in meta-analysis. Statistics in Medicine 2001;20(4):641–54.


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Mattix 2007 Mattix KD, Tataria M, Holmes J, Kristoffersen K, Brown R, Groner J, et al.Pediatric pancreatic trauma: predictors of nonoperative management failure and associated outcomes. Journal of Pediatric Surgery 2007;42:340–4. McGahren 1995 McGahren ED, Magnuson D, Schaller RT, Tapper D. Management of transected pancreas in children. Australian and New Zealand Journal of Surgery 1995;65(4):242–6. Meier 2001 Meier DE, Coln CD, Hicks BA, Guzzetta PC. Early operation in children with pancreas transection. Journal of Pediatric Surgery 2001;36:341–4. Moher 1998 Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al.Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? . Lancet 1998;352:609–13. Moher 2009 Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of Clinical Epidemiology 2009;62(10):1006–12. Moore 1990 Moore EE, Cogbill TH, Malangoni MA, Jurkovich GJ, Champion HR, Gennarelli TA, et al.Organ injury scaling, II: pancreas, duodenum, small bowel, colon, and rectum. Journal of Trauma 1990;30:1427–9.

Seamon 2009 Seamon MJ, Kim PK, Stawicki SP, Dabrowski GP, Goldberg AJ, Reilly PM, et al.Pancreatic injury in damage control laparotomies: Is pancreatic resection safe during the initial laparotomy?. Injury 2009;40(1):61–5. [PUBMED: 19054513] Shilyansky 1998 Shilyansky J, Sena LM, Kreller M, Chait P, Babyn PS, Filler RM, et al.Nonoperative management of pancreatic injuries in children. Journal of Pediatric Surgery 1998;33(2):343–9. Smith 1988 Smith SD, Nakayama DK, Gantt N, Lloyd D, Rowe MI. Pancreatic injuries in childhood due to blunt trauma. Journal of Pediatric Surgery 1988;23(7):610–4. Snajdauf 2007 Snajdauf J, Rygl M, Kalousova J, Kucera A, Petru O, Pycha K, et al.Surgical management of major pancreatic injury in children. European Journal of Pediatric Surgery 2007;17(5): 317–21. Stringer 2005 Stringer MD. Pancreatic trauma in children. British Journal of Surgery 2005;92(4):467–70. Sutton 2006 Sutton E, Bochicchio GV, Bochicchio K, Rodriguez ED, Henry S, Joshi M, et al.Long term impact of damage control surgery: a preliminary prospective study. The Journal of trauma 2006;61(4):831-4; discussion 835-6. [PUBMED: 17033548]

Nadler 1999 Nadler EP, Gardner M, Schall LC, Lynch JM, Ford HR. Management of blunt pancreatic injury in children. The Journal of Trauma 1999;47(6):1098–103. [PUBMED: 10608540]

Takishima 1996 Takishima T, Sugimoto K, Asari Y, Kikuno T, Hirata M, Kakita A, et al.Characteristics of pancreatic injury in children: a comparison with such injury in adults. Journal of Pediatric Surgery 1996;31(7):896–900. [PUBMED: 8811551]

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Thompson 2002 Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted?. Statistics in Medicine 2002;21(11):1559–73.

Penninga 2011 Penninga L, Hillingsø J. Non-operative treatment of severe blunt pancreatic trauma in children [Nonoperativ behandling af alvorlige stumpe pancreaslæsioner hos børn]. Ugeskrift for Læger (Journal of the Medical Danish Association) 2011;173:2346–7.

TSA manual 2011 Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for trial sequential analysis (TSA). www.ctu.dk/tsa/ (accessed 3 December 2013).

Rescorla 1995 Rescorla FJ, Plumley DA, Sherman S, Scherer LR III, West KW, Grosfeld JL. The efficacy of early ERCP in pediatric pancreatic trauma. Journal of Pediatric Surgery 1995;30(2): 336–40. Schulz 1995 Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Journal of the American Medical Association 1995;273 (5):408–12.

Vane 2009 Vane DW, Kiankhooy A, Sartorelli KH, Vane JL. Initial resection of potentially viable tissue is not optimal treatment for grades II-IV pancreatic injuries. World Journal of Surgery 2009;33(2):221–7. Wales 2001 Wales PW, Shuckett B, Kim PC. Long-term outcome after nonoperative management of complete traumatic pancreatic transection in children. Journal of Pediatric Surgery 2001;36 (5):823–7. Wetterslev 2008 Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in


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DG, et al.Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ 2008;336 (7644):601–5. Wood 2010 Wood JH, Partrick DA, Bruny JL, Sauaia A, Moulton SL. Operative vs nonoperative management of blunt pancreatic trauma in children. Journal of Pediatric Surgery 2010;45(2): 401–6. [PUBMED: 20152361] ∗ Indicates the major publication for the study


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DATA AND ANALYSES This review has no analyses.

ADDITIONAL TABLES Table 1. Pancreatic organ injury scale of the American Association for the Surgery of Trauma

Grade

Injury

Description

I

Haematoma

Minor contusion without duct injury

Laceration

Superficial laceration without duct injury

Haematoma

Major contusion without duct injury or tissue loss

Laceration

Major laceration without duct injury or tissue loss

III

Laceration

Distal transection or parenchymal injury with duct injury

IV

Laceration

Proximal transection or parenchymal injury involving ampulla

V

Laceration

Massive disruption of pancreatic head

II

Table 2. Treatment of blunt pancreatic trauma in children, grade I to II

Primary au- Year, country thor

Number of Treatment children (n), grade

Mortality

Pancreas-reOther compli- Success lated complica- cations NOM tions

Juric 2009

7, grade I-II

0%

43% (Grade ll, 43% (2 sepsis, 1 100% pseudocysts) pleural effusion)

2009, Croatia

NOM

of

NOM: non-operative management; OM: operative management. ’Success of NOM’ was defined as primary NOM where no secondary surgery was needed.

Table 3. Treatment of blunt pancreatic trauma in children, grade III to V



Canty 2001

18, grade III- 9 OM 11% (severe OM 0% IV vs. 7 NOM, 2 head trauma) NOM 100% deaths

2001, USA

Mortality

Pancreas-reOther com- Success lated compli- plications NOM cations


-

of

29%

14

Table 3. Treatment of blunt pancreatic trauma in children, grade III to V

(Continued)

Keller 1997

1997, USA

154, grade I-V Grade I-II: 26 8% OM vs. 97 NOM Grade III-V: 16 OM vs. 15 NOM

Grade I-II: 10% Grade III-V: 32%

Wales 2001

2001, Canada

9, grade III-V

44%

9 NOM

0%

-

33% 100% (subphrenical abscess, sepsis occurred twice)

’-’ indicates that it was not possible to extract data from the given study. NOM: non-operative management; OM: operative management; TPN: total parenteral nutrition. ’Success of NOM’ was defined as primary NOM where no secondary surgery was needed.

Table 4. Treatment of blunt pancreatic trauma in children, grade I to V or not specified



Mortality

Pancreas-reOther com- Success lated compli- plications NOM cations

Wood 2010

2010, USA

44, grade I-IV 14 OM vs. 4% (multi- OM 21% vs. OM 57% vs. 29 NOM, 1 trauma) NOM 73% NOM 20% death

Fabbro 2001

2001, Italy

9

Bass 1991

2 OM vs. 7 0% NOM

OM 50% vs. NOM 71%

1991, South 40 Africa

8 OM vs. 32 0% NOM

NOM 38%

Bass 1988

1988, Canada

11 OM vs. 15 0% NOM

OM 18% vs. NOM 53%

de Blaauw 2008

2008, The 34, grade I-IV 3 OM vs. 31 0% Netherlands NOM

Firstenberg 1999

1999, USA

12, grade I-V

7 OM vs. 5 17% (multi- 42% NOM organ injury)

Gorenstein 1987

1987, Canada

21

8 OM vs. 13 10% (aorta OM 25% vs. NOM laceration, NOM 77% head trauma)

26

of

86%

OM 13% (res- 100% piratory stop, abscess) 93%

OM 66% vs. NOM 13% 90% NOM 45% (sepsis)


-

-

77%

15

Table 4. Treatment of blunt pancreatic trauma in children, grade I to V or not specified

(Continued)

Graham 2000

2000, Scotland

16

1 OM vs. 15 0% NOM

NOM 67%

-

80%

Holland 1999

1999, Australia

14

14 NOM

NOM 57%

-

79%

Nadler 1999

1999, USA

51

27 OM vs. 24 NOM

-

-

79%

Kouchi 1999

1999, Japan

20

1 OM vs. 19 5% (acidosis NOM 50% NOM after TPN)

-

84%

Mattix 2007

2007, USA

173, grade I-V 43 OM vs. 130 NOM

-

-

74%

Shilyansky 1998

1998, Canada

28, grade I-V

28 NOM

36%

4% (pelvic ab- 100% scess)

Stringer 2005

2005, UK

9, grade I-IV

1 OM vs. 8 0% NOM

OM 0% vs. OM 100% 38% NOM 100% (sepsis)

Takishima 1996

1996, Japan

8

1 OM vs. 7 0% NOM

OM 100% vs. NOM 14.3%

0%

0%

100%

’-’ indicates that it was not possible to extract data from the given study. NOM: non-operative management; OM: operative management; TPN: total parenteral nutrition. ’Success of NOM’ was defined as primary NOM where no secondary surgery was needed.

CONTRIBUTIONS OF AUTHORS All authors have contributed to the review, and accepted the final version of the review.

DECLARATIONS OF INTEREST None known.


16

SOURCES OF SUPPORT

Internal sources • Rigshospitalet Research Council, Rigshospitalet, Copenhagen, Denmark. Grant to LP

External sources • No sources of support supplied

DIFFERENCES BETWEEN PROTOCOL AND REVIEW The following outcome measure has been moved from secondary outcome to primary outcome: Pancreatic complications (pancreatic pseudocysts, fistulas, pancreatitis, abscesses). We changed the objective to all blunt pancreatic trauma in children, instead of only grade III to V.


17

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