**2. Clinical manifestations of chronic pancreatitis and their management**

## **2.1 Abdominal pain**

*Pancreatitis*

new definition of CP was proposed, according to which CP is a fibro-inflammatory syndrome, affecting people with genetic, environmental and/or other risk factors, resulting in a persistent pathological response as a result of parenchymal injury or stress. In addition, some of the following features of advanced CP may be present in each patient: pancreatic atrophy, fibrosis, pain syndrome, ductal stricture, calcifications, pancreatic exocrine/endocrine insufficiency and dysplasia. The frequency of CP per year in the European population is 5–10/100,000. Alcohol abuse is the most observed cause. Recurrent episodes of acute pancreatitis and heredity as a contrib-

Pain is the most frequent symptom in CP patients, leading to quality of life impairment. It pathogenesis is still poorly understood. Multimodal approach, including lifestyle changes, medical therapy, pancreatic endoscopic and surgical procedures, and other non-pharmacological options are recommended [8, 9]. The pancreatic enzymes lipase, amylase, trypsin and chymotrypsin, released predominantly by the duodenal mucosa exposure of nutrients—especially lipids, are at a great importance for the macronutrient digestion. Their secretion comprises the following three phases—maximum, stable and basic secretion. Pancreatic enzymes amount and action duration depend on the caloric content maldigestion,

Pancreatic exocrine insufficiency (PEI) due to a progressive loss of acinar cells is a functional limitation of pancreatic enzyme and bicarbonate secretion, regardless its etiology, leading to digestive process deficiency. Main pathological mechanisms in adults are (1) Insufficient pancreatic secretory capacity, (2) Decreased gland stimulation, (3) Impaired enzymes release in the duodenum. The causes are divided into primary (chronic pancreatitis, cystic fibrosis, pancreatic agenesia, congenital pancreatic hypoplasia, Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, pancreatic lipomatosis or atrophy, isolated lipase or co-lipase deficiency, pancreatic carcinoma, pancreatic resection) and secondary (reduced cholecystokinin releasing, somatostatinoma or exogenous administration of somatostatin, gastrinoma, (sub) total gastrectomy, resections and Billroth II anastomosis, periam-

Although not studied in-depth, the reported prevalence of PEI in patients with CP varies widely between 40 and 94%. The onset of PEI depends on the CP etiology and is about 10–15 years (5–6 years for alcoholic CP) after initiating the pathological CP processes, which is explained by the large functional reserve capacity. Decompensation occurs when the enzyme secretion is reduced by 90–95%. However, in some patients PEI symptoms such as malnutrition and/or abdominal symptoms (diarrhea, flatulence, pain), steatorrhea, body weight loss are first

Although steatorrhea is a typical symptom of a severe PEI, no clinical symptom unambiguously proves or excludes PEI. Steatorrhea may be absent or caused by pancreatic duct obstruction, low duodenal pH, decreased contact time due to increased motility, small intestinal bacterial overgrowth. Fat-soluble vitamin insufficiency, protein malnutrition, increased risk of osteoporosis and fractures, life-threatening complications such as cardiovascular events are further PEI

An up-to-date assessment of pancreatic exocrine function allows diagnosis of PEI, initiation of pancreatic enzyme replacement therapy (PERT) and its monitoring. Pancreatic exocrine secretion can be assessed by direct and indirect methods. Direct tests are based on determination of volume, bicarbonates and/ or enzymes in the stimulated pancreatic gland by intravenous administration of hormones or their peptide analogs. These methods are invasive because duodenal

uting factor may result into CP development [1–7].

the food type and its physical properties [1, 6, 7, 10, 11].

pullary tumors) [11–15].

appearance of the disease [1, 7, 16–18].

complications [2, 5, 19–22].

**36**

Abdominal pain is a predominant symptom, affecting 80–90% of patients with CP. Pain significantly reduce quality of life. Pathogenesis is still poorly understood. Multifactorial mechanisms are proposed, including inflammation; duct obstruction followed by hypertension and ischemia; neuronal damage—neuropathic and dysfunctional pain due to hypersensitivity, central and spinal nociceptive neurons alterations. Alcohol and tobacco have contributing role for pain exacerbation. Pancreatic pain covers the characteristics of visceral pain—diffuse severe dull persistent pain, usually with epigastrium location and further radiation to the back, left or right hypochondria. Pain is not necessarily linked to a new acute episode and often worsens with food intake. Pain could be recurrent, during acute episodes and prolonged. Questionnaire scales could be used for pain characterization: Izbicki pain score, brief pain inventory (validated for CP), quantitative sensory testing. According to newest guidelines a multi-modal approach, including lifestyle changes, medical therapy and non-pharmacological approaches, is recommended. Alcohol and tobacco cessation should be advised in all patients. PERT could release pain in patients with ductal obstruction as oral enzymes reduce cholecystokinin levels and therefore decrease pancreatic juice secretion, leading otherwise to duct hypertension. A combination of antioxidants is useful to reduce the oxidative stress and damage. According to the published in 1986 WHO stepwise analgesic's approach is recommended. Simple

#### *Pancreatitis*

analgesics (Paracetamol, NSAIDs, Aspirin) are first-line drugs with Paracetamol being the preferable one. If no pain relief is achieved, weak opioids (Tramadol), strong opioids (Morphine, Oxycodone), gabapentinoids (Pregabalin), antidepressants or *N*-methyl-d-aspartate receptor antagonists (Ketamine) could be used. Endoscopic treatment with or without Extracorporeal Shock Wave Lithotripsy has a beneficial role in cases with duct obstruction (see below). If endoscopic treatment is ineffective, surgery procedures (drainage, partial or total resection) are indicated. Better results are observed, when applied in early stages of CP and in patients with no opioids requirements. Other non-pharmacological options in selected patients include bilateral thoracoscopic splanchnicectomy, celiac plexus blocks and splanchnic nerve ablation, spinal cord stimulation, transcranial magnetic stimulation, psychological therapies [8, 9].
