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Home , Malabsorption, Pancreatectomy, Pancreatic disease

JOP. J (Online) 2007; 8(2):151-155.

EDITORIAL

Medical Therapy of in Patients with Head Pancreatic Resection

Laura Bini1, Lorenzo Fantini1, Raffaele Pezzilli1, Davide Campana1, Paola Tomassetti1, Riccardo Casadei2, Lucia Calculli3, Roberto Corinaldesi1

Departments of 1Digestive Diseases and Internal , 2Surgery, and 3Radiology, Sant’Orsola-Malpighi Hospital. Bologna, Italy

Introduction the ; on the other hand, and lipases are more stable [6, 7, 8]. Exocrine pancreatic insufficiency caused by There are various explanations for the loss of pancreatic resection results from various enzymatic action of the enzymatic activity factors which regulate and during progression in the intestinal lumen: absorption of . Pancreatic function proteolytic degradation ( is the has been extensively studied in the last 40 main lipase degradation factor) [9], lipase years even if some aspects of secretion and acid inactivation (lipase is particularly gastrointestinal adaptation after pancreatic sensitive to acid inactivation) [10], and the resection are not completely understood. The brief half life of some , particularly pancreatic gland normally secretes more than lipase [11]. This is the reason why, in patients 2 liters of juice per day which is constituted of with exocrine pancreatic insufficiency, water, bicarbonates and enzymes [1]; maldigestion is more severe than that of secretion per gram of pancreatic tissue is and . more elevated than that of any other organ [2] In addition to an optimal concentration of and more than 85% of the protein content is biliary acids and colipases in the intestinal constituted of enzymes which are able to lumen, good fat digestion requires an digest lipids, proteins and carbohydrates [3]. adequate blending of nutrients with the The pancreas normally produces more and optimal intestinal enzymes than are necessary for food digestion motility. [1] and normal digestion is guaranteed up to a In pathologic conditions, such as chronic loss of 95% of pancreatic secretive capacity , there is a deficit in bicarbonate [4]. Recently, French authors [5] have production; a low duodenal pH determines demonstrated that gastric lipase can biliary acid precipitation and the remaining compensate pancreatic lipase even if it is not lipase activity worsens. capable of complete lipolytic activity. Finally, other causes of malabsorption may be degradation in the intestinal lumen is an accelerated gastric emptying and a lower the main factor for controlling intestinal time of transit [12, 13]. absorption. The activity of pancreatic Pancreatic Function after Pancreatic enzymes progressively decreases during their Resection Due to Neoplasia progression in the intestinal lumen: 60% of active trypsin and chymotrypsin are present in and carried out the whereas only 20 % are present in for neoplastic diseases can determine

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 2 - March 2007. [ISSN 1590-8577] 151 JOP. J Pancreas (Online) 2007; 8(2):151-155. pancreatic insufficiency and . The Clinical Manifestations and Diagnosis of majority of patients with pancreatic neoplasia Exocrine Pancreatic Insufficiency undergo the Whipple technique. Factors responsible for exocrine pancreatic The main clinical manifestations of exocrine insufficiency are the extension of the pancreatic insufficiency are fat malabsorption, pancreatic resection and a pancreatic duct called steatorrhea, which consists of fecal occlusion which determines fibrosis and excretion of more than 6 g per day of fat, atrophy of the remaining gland. , abdominal pain and abdominal The extension of the resection is important for swelling sensation. Fat malabsorption also gland insufficiency; we know that patients determines a deficit of fat-soluble who undergo radical pancreatectomy have a (A, D, E, K) with the consequent clinical more severe exocrine pancreatic insufficiency manifestations. than patients who undergo standard pancreatic The diagnosis of exocrine pancreatic resection [14]. insufficiency is based on these clinical symptoms and signs observed with direct and indirect tests. Some of these tests can be used Pancreatic Function after Pancreatic to determine the degree of insufficiency Resection for (classified as mild, moderate and severe). The

most sensitive test is the secretin-CCK or The majority of patients with chronic secretin-cerulein test; it has a double-lumen pancreatitis have an exocrine pancreatic tube capable of separately draining the gastric insufficiency before the operation. The type juice and the pancreatic juice. The test starts of operation in that group of patients depends with pancreatic stimulation by secretin which on the type of pancreatic lesion and on the produces the hydro- pancreatic expertise of the surgeon. The Whipple secretion, and CCK or cerulean which can technique is generally preferred for lesions stimulate enzymatic secretion. This test is situated in the head of the pancreas and highly sensitive and specific [20] but it is approximately 50% of these patients develop invasive, lengthy and expensive; moreover, it severe pancreatic insufficiency [15, 16]. The is possible only in patients with a normal Whipple technique requires a complete and it is not useful in reconstruction of the digestive tract through patients with an altered digestive . At the creation of a pancreaticojejunostomy, a present, fecal chymotrypsin and 1 are hepatico Roux-en-Y and a more frequently used [21]. In particular, . In this way physiologic elastase 1 determination is more sensitive and gastric emptying and the mixing of food, specific than chymotrypsin. The advantage of enzymes and biliary acids are altered due to these tests is that they can be used in patients the pyloric and duodenal resection. A pylorus- who have undergone involving the preserving pancreatectomy such as the Berger gastro-intestinal tract, but they cannot reveal a technique which saves the and the mild degree of exocrine pancreatic and has a more physiologic gastric insufficiency [21]. A cholesteryl-octanoate emptying is an operation capable of breath test is rarely used because of its high maintaining the intestinal anatomy and cost and possible interference with metabolic physiology [17]; this is confirmed by various and pulmonary diseases [22]. Fecal fat studies which demonstrate a minimum determination is useful in monitoring lipid pancreatic insufficiency caused by this type of malabsorption therapy. Pancreatic exocrine operation [18]. evaluation during magnetic resonance However, if the is diffuse, cholangiopancreatography with secretin a total or subtotal pancreatectomy may be administration is still under study and the necessary with consequent obvious exocrine results of the published studies seem to be and endocrine insufficiency [19]. promising [23].

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 2 - March 2007. [ISSN 1590-8577] 152 JOP. J Pancreas (Online) 2007; 8(2):151-155.

Exocrine Pancreatic Insufficiency Therapy and they facilitate fat digestion [28, 29]. after Pancreatectomy Pancreatic extracts constituted of fungal or bacterial lipases resistant to acid are now The medical therapy target is to correct fat, being developed; these preparations have protein and malabsorption with already been tried successfully in steatorrhea pancreatic extracts, and secondary therapy and they represent the future of mellitus with . Limitation of fat substitutive therapy [30]. ingestion is not necessary in most cases. There are now many studies of exocrine Pancreatic enzyme preparations should have pancreatic insufficiency secondary to an adequate concentration of lipases, pancreatic resection. The efficacy of amylases and proteases. The release of commercial pancreatic extract preparations 20,000-30,000 U of lipases in the duodenum depends on the type of resection. In a non- seems to be an optimal dosage for correcting randomized study carried out [31] on patients steatorrhea, even if it is necessary to double with pylorus-preserving pancreaticoduoden- the dosage to optimize digestion and fat ectomy for pancreatic neoplasia, gastro- absorption. It is possible that the steatorrhea protected microspheres were less effective does not respond to increased extract doses than those in patients who had undergone a and that symptoms do not improve [24]. classic Whipple technique. This is possible Gastric acidity seems to be very important in because microspheres are retained in the steatorrhea maintenance; in fact, some stomach and, in this subgroup of patients, it patients with chronic pancreatitis have gastric would be better to use powdered enzymatic acid hypersecretion and, in many patients preparations to optimize their efficacy. One of with chronic pancreatitis, the gastric acid is the few randomized studies explaining the not buffered because of the reduction of efficacy of pancreatic extracts for the control bicarbonates in the pancreatic juice. In this of malabsorption was carried out in a small case, the lipase is rapidly destroyed in the group of patients with chronic pancreatitis stomach and duodenum because of its who had undergone pancreaticojejunostomy inactivation at a low pH. For this reason, there [32]. All the patients studied had an exocrine are now acid resistant preparations which can pancreatic insufficiency evaluated using fecal release the enzymes only when the luminal fat determination and the degree of fat pH is more than 6. Moreover, it is possible to malabsorption; in these patients, treatment increase luminal pH with H2 antagonists or with pancreatic extracts ameliorated not only proton pump inhibitors to better protect the nitrogen balance but also fat and protein lipase from the gastric acid [25]. Another absorption. Another randomized controlled therapeutic problem is the enzyme-food double-blinded crossover study, explored the mixing and its correct and synchronous comparative efficacy of two pancreatin passage into the duodenum. Under normal preparations of gastroprotected microspheres conditions, food passes into the duodenum as with different doses (Creon® 25.000 and particles having a diameter of 2 mm [26]. For Creon® 8.000) in pancreatectomized patients this reason, pancreatic extracts are constituted with chronic pancreatitis [33]. All patients of 1-1.5 mm gastroprotected microspheres; were stabilized before enrolment in the study recent studies demonstrate that these with a standard dose of pancreatic extracts. formulations can pass into the duodenum After this stabilization period, 56% of the together with food, even if microspheres patients still had a fecal fat excretion greater sometime pass into the duodenum before than 7 g/day, and 38% greater than 15 g/day. solid food [27] since gastric emptying is very The results demonstrate that there is a variable in any subject and this can decrease significant relationship between fecal fat the efficacy of their action. Microsphere excretion, fecal volume and evacuation preparations have demonstrated a superior frequency but there is not a relationship efficacy as compared to other preparations, between fecal fat excretion and abdominal

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 2 - March 2007. [ISSN 1590-8577] 153 JOP. J Pancreas (Online) 2007; 8(2):151-155. pain or malabsorption symptoms. The References majority of patients with steatorrhea were also 1. Gullo L, Pezzilli R, Priori P, Baldoni F, Paparo F, being treated with antiacids, and some Mattioli G. Pure pancreatic juice collection over 24 patients took more than 50 capsules of consecutive hours. Pancreas 1987; 2:620-3. [PMID pancreatic extracts per day. Both the 3671350] pancreatin standard dose and the elevated 2. Rinderknecht H. Pancreatic secretory enzymes in dose demonstrated equal efficacy; in the exocrine pancreas. In: Go VLW, ed. The exocrine pancreatectomized patients, high dose pancreas: biology, pathobiology and diseases. New York: Raven Press, 1986:163-83. pancreatic extracts significantly reduced the number of capsules needed per day with a 3. Desnuelle P, Figarella C. Biochemistry. In: Howat HAT, Sarles H, eds. The exocrine pancreas. better compliance to substitutive therapy. Philadelphia: WB Saunders, 1978:86-112.

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 2 - March 2007. [ISSN 1590-8577] 155