Pancreatic enzyme replacement therapy for steatorrhoea in pancreatic cancer
Appendices
Appendix 1. Glossary of terms
Alkaline phosphatase: any of the phosphatases (as phosphomonoesterase from blood plasma or milk) optimally active in an alkaline medium and occurring in especially high concentrations in bone, liver, kidneys, or placenta
Amylase: any of a group of enzymes (as amylopsin) that catalyse (mediate) the hydrolysis (chemical process of decomposition involving the splitting of a bond and the addition of the hydrogen cation and the hydroxide anion of water) of starch and glycogen (a white amorphous tasteless polysaccharide (C6H10O5)x that constitutes the principal form in which glucose is stored in animal tissues) or their intermediate hydrolysis products
Anastomosed: connected or joined by anastomosis (the surgical union of parts and especially hollow tubular parts)
Bilirubin: a reddish yellow pigment (C33H36N4O6) that occurs especially in bile and blood, and causes jaundice if accumulated in excess
BMI: body mass index, a measure of body fat that is the ratio of the weight of the body in kilograms to the square of its height in meters
Body of the pancreas: the largest part of the pancreas, located between the neck and tail of the pancreas
BRCA2: a tumour suppressor gene that in mutated form tends to be associated with an increased risk of certain cancers and especially breast and ovarian cancers
Cachexia: loss of skeletal muscle mass with or without the loss of fat mass
Chemotherapy: the use of chemical agents in the treatment or control of disease or mental disorder
Common bile duct: the duct formed by the union of the hepatic and cystic ducts, and opening into the duodenum
Common hepatic duct: the duct formed by the convergence of the right hepatic duct (which drains bile from the right functional lobe of the liver) and the left hepatic duct (which drains bile from the left functional lobe of the liver). The common hepatic duct then joins the cystic duct coming from the gallbladder to form the common bile duct
Concomitant: accompanying or associated with
Diabetes mellitus: a variable disorder of carbohydrate metabolism caused by a combination of hereditary and environmental factors, and usually characterised by the inadequate secretion or utilisation of insulin, excessive urine production, excessive amounts of sugar in the blood and urine, and by thirst, hunger, and loss of weight
Distal: refers to parts of the body further away from the centre
Duodenum: the first, shortest, and widest part of the small intestine, which in humans is about 25 cm long, and which extends from the pylorus (the opening from the vertebrate stomach into the intestine) to the undersurface of the liver, where it descends for a variable distance, receives the bile and pancreatic ducts, and then bends to the left and finally upward to join the jejunum
Endocrine: secreting internally and specifically producing secretions that are distributed in the body by way of the bloodstream
Exocrine: producing, being, or relating to a secretion that is released outside its source
FAMMM: familial atypical multiple mole melanoma (a type of skin cancer) syndrome
Gall bladder: a membranous muscular sac in which bile from the liver is stored
Gastric: relating to the stomach
Head of the pancreas: the portion of the pancreas that is lodged within the curve of the duodenum and is flattened anteriorly (from before)
Histological: related to microscopic tissue structure or organisation
HNPCC: hereditary non‐polyposis (characterised by the absence of polyps) colorectal cancer
Incidence: act of occurring
Invasive: tending to spread and especially tending to invade healthy tissue
Jaundice: a yellowish pigmentation of the skin, tissues, and certain body fluids caused by the deposition of bile pigments that follows interference with the normal production and discharge of bile (as in certain liver diseases) or the excessive breakdown of red blood cells (as after internal haemorrhage (bleeding) or in various haemolytic states (related to the lysis of red blood cells))
Jejunum: the section of the small intestine that comprises the first two‐fifths beyond the duodenum and that is larger, thicker‐walled, and more vascular, and has more circular folds and fewer Peyer's patches (numerous large oval patches of closely aggregated nodules of lymphoid tissue in the walls of the small intestine especially in the ileum) than the ileum
Lipase: any enzyme (secreted by the pancreas) that catalyses (mediates) the breakdown of fats and lipoproteins (conjugated proteins composed of a complex of protein and lipid) usually into fatty acids and glycerol (a sweet syrupy hygroscopic trihydroxy alcohol C3H8O3 usually obtained by the saponification of fats)
Luminal: relating to a lumen, the cavity of a tubular organ or part
Malabsorption: faulty absorption of nutrient materials from the alimentary canal (digestive tract)
Maldigestion: imperfect or impaired digestion
Malignant: tending to infiltrate, metastasize, and terminate fatally
Malnutrition: faulty nutrition due to inadequate or unbalanced intake of nutrients or their impaired assimilation or utilisation
Metabolism: chemical changes in living cells by which energy is provided for vital processes and activities, and new material is assimilated
Metastasised: spread by metastasis, the spread of a disease‐producing agent (e.g. cancer cells or bacteria) from the initial or primary site of disease to another part of the body
Morbidity: a diseased state or symptom
Mortality: death or the quality or state of being subject to death
Mutation: a relatively permanent change in hereditary material involving either a physical change in a chromosome (linear body of the cell nucleus of eukaryotic organisms that takes up basophilic stains and contains most or all of the genes of the organism) or a biochemical change in the codons (specific sequences of three consecutive nucleotides that are part of the genetic code and that specify a particular amino acid in a protein or start or stop protein synthesis) that make up genes and also the process of producing a mutation
Non‐enteric coated: not containing a coating to prevent breakdown in the stomach
Obstructive jaundice: jaundice due to obstruction of the biliary passages (as by gallstones or tumours)
Oncogene: a gene having the potential to cause a normal cell to become cancerous
Osteomalacia: a disease of adults that is characterised by softening of the bones; analogous to rickets in the young
Pancreatic duct: a duct connecting the pancreas with the intestine
Pancreatic exocrine insufficiency (PEI): a condition characterised by deficiency of the exocrine pancreatic enzymes, resulting in the inability to digest food properly
Pancreatitis: inflammation of the pancreas
PERT: pancreatic enzyme replacement therapy
Peutz‐Jeghers: a familial polyposis condition characterised by the presence of numerous polyps (projecting masses) in the stomach, small intestine, and colon, and by melanin‐containing spots on the skin and mucous membranes, especially the lips and gums. Melanin is any various black, dark brown, reddish brown, or yellow pigment of animal or plant structures
Physiology: the organic processes and phenomena of an organism or any of its parts, or of a particular bodily process
Precancerous: tending to become cancerous
Prognosis: the prospect of survival and recovery from a disease as anticipated from the usual course of that disease or indicated by special features of the case
Protease: any of numerous enzymes that hydrolyse (cause the chemical process of decomposition involving the splitting of a bond and the addition of the hydrogen cation and the hydroxide anion of water) proteins and are classified according to the most prominent functional group (a serine or cysteine) at the active site
Quality of life: the standard of health, comfort, and happiness experienced by an individual or group
Radiotherapy: the treatment of disease by means of radiation (as X‐rays)
Ras: any of a family of genes that undergo mutation to oncogenes (genes having the potential to cause a normal cell to become cancerous) and especially to some commonly linked to human cancers (e.g. the colon, lung, and pancreas)
Resection: the surgical removal of part of an organ or structure
Risk factor: something that increases risk or susceptibility
Sarcopenia: loss in skeletal muscle mass
Serum: the clear yellowish fluid that remains from blood plasma (liquid portion of blood in which red and white blood cells and platelets are suspended) after clotting proteins have been removed
Skeletal muscle: striated muscle that is usually attached to the skeleton and is usually under voluntary control
Steatorrhoea: an excess of fat in the stool
Survival rate: a part of survival analysis, indicating the percentage of people in a study or treatment group who are alive for a given period of time after diagnosis
Tail of the pancreas: the part of the pancreas located anatomically left near the hilum of the spleen
Tumour marker: a biomarker (a distinctive biological or biologically derived indicator of a process, event, or condition) found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types
Tumour‐suppressor gene: any of a class of genes (such as p53) that act in normal cells to inhibit unrestrained cell division and that when inactivated (as by mutation) place the cell at increased risk of malignant proliferation
Whipple’s procedure: a major surgical operation involving the pancreas, duodenum, and other organs
Appendix 2. CENTRAL search strategy
#1 MeSH descriptor: [Pancreatic Neoplasms] explode all trees
#2 Pancrea* near/5 (cancer* or carcin* or malig* or tumor* or tumour* or neoplas*) (Word variations have been searched)
#3 #1 or #2
#4 MeSH descriptor: [Amylases] explode all trees
#5 Pancrea* near/5 (enzyme* or amylase* or lipase* or protease or phospholipase* or trypsin* or chymotrypsin*) (Word variations have been searched)
#6 enzyme replacement or enzyme supplement* or "PERT" or "PEPs" (Word variations have been searched)
#7 pancrelipase or pancreatin or Creon or Pancreaze or Zenpep or Pancrecarb or TheraCLEC‐Total or Panokase or plaretase or Lipram or Pangestyme or Ku‐Zyme or Palcaps or Pangestyme or Panocaps or Pancrease MT (Word variations have been searched)
#8 pancrinase or nutrizym 22 or Cotazym or Dygase or Kutrase or Lapase or Pertzye or ultracaps or viokace or Viokase or ultresa or Ultrase (Word variations have been searched)
#9 #4 or #5 or #6 or #7 or #8
#10 #3 and #9
Appendix 3. MEDLINE search strategy
1 exp Pancreatic Neoplasms/
2 (Pancrea* adj5 (cancer* or carcin* or malig* or tumor* or tumour* or neoplas*)).tw,kw.
3 1 or 2
4 exp steatorrhea/
5 (steatorrhea or steatorrhoea).tw,kw.
6 ((fat or fatty or oily) adj5 (feces or faeces or fecal or faecal or stool or stools)).tw,kw.
7 4 or 5 or 6
8 3 and 7
9 exp Amylases/
10 (Pancrea* adj5 (enzyme* or amylase* or lipase* or protease or phospholipase* or trypsin* or chymotrypsin*)).tw,kw.
11 (enzyme replacement or enzyme supplement* or "PERT" or "PEPs").tw,kw.
12 (pancrelipase or pancreatin or Creon or Pancreaze or Zenpep or Pancrecarb or TheraCLEC‐Total or Panokase or plaretase or Lipram or Pangestyme or Ku‐Zyme or Palcaps or Pangestyme or Panocaps or Pancrease MT).tw,kw.
13 (pancrinase or nutrizym 22 or Cotazym or Dygase or Kutrase or Lapase or Pertzye or ultracaps or viokace or Viokase or ultresa or Ultrase).tw,kw.
14 or/9‐13
15 8 and 14
16 3 and 14
17 randomized controlled trial.pt.
18 controlled clinical trial.pt.
19 random*.ab.
20 placebo.ab.
21 drug therapy.fs.
22 trial.ab.
23 groups.ab.
24 or/17‐23
25 exp animals/ not humans.sh.
26 24 not 25
27 16 and 26
28 15 or 27
Appendix 4. Embase search strategy
1 exp pancreas cancer/
2 (Pancrea* adj5 (cancer* or carcin* or malig* or tumor* or tumour* or neoplas*)).tw,kw.
3 1 or 2
4 exp steatorrhea/
5 (steatorrhea or steatorrhoea).tw,kw.
6 ((fat or fatty or oily) adj5 (feces or faeces or fecal or faecal or stool or stools)).tw,kw.
7 4 or 5 or 6
8 3 and 7
9 exp pancreas enzyme/
10 (Pancrea* adj5 (enzyme* or amylase* or lipase* or protease or phospholipase* or trypsin* or chymotrypsin*)).tw,kw.
11 (enzyme replacement or enzyme supplement* or "PERT" or "PEPs").tw,kw.
12 (pancrelipase or pancreatin or Creon or Pancreaze or Zenpep or Pancrecarb or TheraCLEC‐Total or Panokase or plaretase or Lipram or Pangestyme or Ku‐Zyme or Palcaps or Pangestyme or Panocaps or Pancrease MT).tw,kw.
13 (pancrinase or nutrizym 22 or Cotazym or Dygase or Kutrase or Lapase or Pertzye or ultracaps or viokace or Viokase or ultresa or Ultrase).tw,kw.
14 or/9‐13
15 8 and 14
16 3 and 14
17 random:.tw.
18 clinical trial:.mp.
19 exp health care quality/
20 placebo:.mp.
21 double‐blind:.tw.
22 or/17‐21
23 exp animal/ not human.sh.
24 22 not 23
25 16 and 24
26 15 or 25
Appendix 5. CINAHL search strategy
S19 S14 OR S18
S18 S10 AND S17
S17 S15 OR S16
S16 TX ((fat or fatty or oily) and (feces or faeces or fecal or faecal or stool or stools))
S15 TX steatorrhea or steatorrhoea
S14 S10 AND S13
S13 S11 OR S12
S12 (MH "Randomized Controlled Trials")
S11 TX random*
S10 S3 AND S9
S9 S4 OR S5 OR S6 OR S7 OR S8
S8 TX pancrinase or nutrizym 22 or Cotazym or Dygase or Kutrase or Lapase or Pertzye or ultracaps or viokace or Viokase or ultresa or Ultrase
S7 TX ancrelipase or pancreatin or Creon or Pancreaze or Zenpep or Pancrecarb or TheraCLEC‐Total or Panokase or plaretase or Lipram or Pangestyme or Ku‐Zyme or Palcaps or Pangestyme or Panocaps or Pancrease MT
S6 TX enzyme replacement or enzyme supplement* or "PERT" or "PEPs"
S5 TX Pancrea* and (enzyme* or amylase* or lipase* or protease or phospholipase* or trypsin* or chymotrypsin*)
S4 (MH "Amylases")
S3 S1 OR S2
S2 TX Pancrea* and (cancer* or carcin* or malig* or tumor* or tumour* or neoplas*)
S1 (MH "Pancreatic Neoplasms+")
