Chronic Pancreatitis and Bone Disease.

Patients with chronic pancreatitis (CP) may have a higher prevalence of osteoporosis than the general population thereby increasing the risk of bone fracture. The pathophysiology of bone disease in CP is multifactorial. Their risk factors for secondary osteoporosis include increasing age, low body mass index from sitophobia, maldigestion due to exocrine pancreatic insufficiency (EPI) with resulting low vitamin D, as well as smoking and alcohol abuse. An obvious association of bone disease with CP is from EPI with maldigestion of fat-soluble vitamins including vitamin-D, which has a significant role in the process of bone formation. Vitamin-D deficiency may be higher in CP patients vs controls, and it is especially so in CP patients with EPI. Screening for CP-associated osteopathy, including osteopenia and osteoporosis, should be initiated early in the course of CP, as the overall prevalence of bone disease is approximately two-thirds of CP patients. Our initial approach in the treatment of osteoporosis should include correction of maldigestion resulting from EPI with use of pancreatic enzyme replacement therapy (PERT). PERT, which is the treatment for EPI is associated with improvement in Dual energy X-ray absorptiometry (DXA) values and vitamin-D levels compared to those who are not treated. This should improve, in addition to body mass index, vitamin-D deficiency and calcium absorption as well as improve overall nutritional status. Osteopathy is common in CP patients, has significant associated morbidity, should be screened for regularly, and corrected with fat soluble vitamin supplementation and PERT to prevent clinical sequelae. In this article, we review the epidemiology, pathophysiology, and treatment of bone disease in patients with CP.

Case Report: Vitamin A Deficiency and Nyctalopia in a Patient with Chronic Pancreatitis.

SIGNIFICANCE: Vitamin A deficiency is a known concern in developing countries, but it is often overlooked in developed regions. A history of conditions causing alimentary malabsorption should be considered when patients present with complaints of nyctalopia. PURPOSE: A case of vitamin A deficiency with nyctalopia in a patient with chronic pancreatitis including pertinent diagnostic testing, treatment, and management is presented. The intent is to draw attention to the condition as a differential diagnosis for nyctalopia due to increased prevalence of conditions causing malabsorption. CASE REPORT: A patient with a history of chronic pancreatitis and pancreatic tumor presented with symptoms of nyctalopia and xerophthalmia. Given his systemic history, testing was ordered to determine serum vitamin A levels and retinal function. After results had confirmed depleted vitamin A levels and diminished retinal function, treatment with both oral and intramuscular vitamin A supplementation was initiated to normalize vitamin A levels and improve retinal photoreceptor function. Subjective improvement in symptoms was reported shortly after beginning supplementation, and ultimately, vitamin A levels and retinal function showed improvement after intramuscular treatment. CONCLUSIONS: Detailed case history and a careful review of systems along with serum vitamin A testing and, if available, electroretinography to assess retinal function can help to make a definitive diagnosis. With appropriate comanagement with the patient's primary care physician, it is possible for those with nyctalopia to begin vitamin A supplementation and regain retinal function.

Nutritional Therapy in Chronic Pancreatitis.

Malnutrition is a frequent complication in patients with chronic pancreatitis. Maldigestion as a consequence of pancreatic exocrine insufficiency is the major cause of malnutrition in these patients. Together with that, toxic habits and alterations of the gastroduodenal transit may play a relevant role. Malnutrition in chronic pancreatitis is associated with osteoporosis, sarcopenia, poor quality of life, and increased mortality. An adequate nutritional evaluation including anthropometric, biochemical, and morphologic parameters is recommended in these patients. Nutritional advice and support together with an adequate pancreatic enzyme replacement therapy are indicated.

Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity.

The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted µ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain.

Systematic mechanism-orientated approach to chronic pancreatitis pain.

Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.

[The efficiency of Lyapko applicators usage in the treatment of patients with comorbidity of hypertension and chronic pancreatitis based on the heart rate variability].

Efficiency of the acupressure methodics of Lyapko applicators including in the treatment of patients with comorbidity of hypertension and chronic pancreatitis is estimated based on the study of the dynamics of the clinic and the state of autonomic nervous system using heart rate variability. The significant autonomic disorders were found in the studied group. More pronounced effect of this method of acupuncture was confirmed for the treatment of comorbidity of the studied pathologies, especially with regard to autonomic disorders.

Medical management of pain in chronic pancreatitis.

Chronic pancreatitis is a common disorder caused by various etiological factors. It usually manifests with abdominal pain and exocrine (steatorrhea, malnutrition) or endocrine insufficiency (diabetes mellitus). Abdominal pain is the dominant symptom in these patients. Medical, endoscopic and surgical modalities are available for therapy. This review focuses on the pharmacological approaches to manage pancreatic pain. Before embarking on medical management of pain it is prudent to exclude complications like pancreatic cancer, pseudocysts, inflammatory mass, biliary or duodenal obstruction which may contribute to abdominal pain. Pharmacological measures for pain relief include central analgesics, enzyme supplements and antioxidants. Other measures include endoscopic and surgical therapy which are not discussed here. Appropriate management of exocrine and endocrine insufficiency and successful control of diabetes are also important in the management of chronic pancreatitis.

Pain in chronic pancreatitis: managing beyond the pancreatic duct.

Chronic pancreatitis (CP) continues to be a clinical challenge. Persistent or recurrent abdominal pain is the most compelling symptom that drives patients to seek medical care. Unfortunately, in spite of using several treatment approaches in the clinical setting, there is no single specific treatment modality that can be earmarked as a cure for this disease. Traditionally, ductal hypertension has been associated with causation of pain in CP; and patients are often subjected to endotherapy and surgery with a goal to decompress the pancreatic duct. Recent studies on humans (clinical and laboratory based) and experimental models have put forward several mechanisms, including neuroimmune alterations, which could be responsible for pain. This might explain the partial or no response to single modality treatment in a significant proportion of patients. The current review discusses the recent concepts of pain generation in CP and evidence based therapeutic approaches (other than ductal decompression) to handle persistent or recurrent pain. We focus primarily on parenchymal and neural components; and discuss the role of antioxidants and the existing controversies, drugs that interfere with neural transmission, pancreatic enzyme supplementation, celiac neurolysis, and pancreatic resection procedures. The review concludes with the treatment approach that we follow at our institute.

Long-term outcomes after Frey's procedure for chronic pancreatitis with an inflammatory mass of the pancreatic head, with special reference to locoregional complications.

BACKGROUND: Frey's procedure might be a good alternative to pylorus-preserving pancreaticoduodenectomy (PPPD) for patients with an inflammatory mass of the head of the pancreas, because it is technically easy and associated with low morbidity and good pain relief. PURPOSE: To analyze the short-term and long-term outcomes of Frey's procedure in comparison with PPPD and to evaluate the efficacy of Frey's procedure against preoperative locoregional complications. PATIENTS AND METHODS: From August 1997 through December 2007, 6 patients underwent Frey's procedure (as described by Frey and Smith), and 10 patients underwent PPPD. The mean follow-up times were 70.8 months (Frey's procedure) and 119.8 months (PPPD). Preoperative biliary stricture and duodenal stenosis were observed in 4 and 3 patients, respectively, of patients undergoing Frey's procedure. Pain intensity was assessed with a pain scoring system. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of-Life Questionnaire-Core 30. Exocrine and endocrine pancreatic function was measured during follow-up. RESULTS: Significant reductions in total pain scores and all QOL scale scores were observed immediately after surgery in all patients (P<0.05). Frey's procedure was superior to PPPD with regard to physical status 7 years after surgery (P<0.05). One patient in the Frey group had a grade B pancreatic fistula, and 2 patients in the PPPD group had intra-abdominal bleeding and delayed gastric emptying. There were no re-operations or surgery-related deaths in either group. Diabetes developed postoperatively in 2 patients in the PPPD group. No patients with preoperative duodenal or biliary stricture or both had a relapse. Three patients in the PPPD group died during follow-up of diseases unrelated to chronic pancreatitis. CONCLUSION: Frey's procedure is safe and effective with regard to pain relief, preservation of pancreatic function, and improvement of QOL over the long term. Moreover, this procedure can also be used to treat preoperative biliary stricture and duodenal stenosis associated with an inflammatory mass of the pancreatic head.

Spinal cord stimulation for visceral pain from chronic pancreatitis.

BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with various chronic abdominal pain syndromes including chronic pancreatitis. Here described is a large clinical experience in SCS for severe chronic pancreatitis. METHODS: SCS was trialed in 30 patients with chronic pancreatitis. SCS trials lasted 7-14 days (median 9 days). SCS lead tips were mostly positioned at the T5 (N= 10) or T6 (N= 10) vertebral level. RESULTS: Twenty-four patients (80%) reported at least 50% pain relief on completion of the trial. Among these, pre-trial visual analog scale (VAS) pain scores averaged 8 ± 1.6 (standard deviation) and opioid use averaged 165 ± 120 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.67 ± 2 cm (p < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 105 ± 101 mg morphine equivalent a day. Six patients failed the trial; one was lost to follow-up; in three patients after the implantation, the system had to be removed due to infection or lead migration; and 20 were followed for the whole year. For 20 patients followed for the whole year, VAS pain scores remained low (3.6 ± 2 cm; p < 0.001) at one year, as did opioid use (48.6 ± 58 mg morphine equivalents). CONCLUSIONS: SCS may be a useful therapeutic option for patients with severe visceral pain from chronic pancreatitis. Prospective trial is warranted.

Oxalate nephropathy associated with chronic pancreatitis.

BACKGROUND AND OBJECTIVES: Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. RESULTS: Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. CONCLUSION: AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.

[Types of microcirculation and laser therapy in chronic pancreatitis].

The aim of the study was to evaluate effect of low-intensity laser therapy (LILT) on systemic circulation in patients with chronic pancreatitis (CP) in the phase of exacerbation. 65 patients aged 36-77 years were divided into study (n = 20) and control (n = 45) groups. In addition, 30 healthy subjects were examined. Patients of the study group received drug therapy combined with intravenous blood or skin laser irradiation. Controls were treated with medicinal preparations alone. CP was diagnosed based on characteristic pain syndrome, compromised secretory function of the pancreas, results of laboratory and instrumental analysis. Microcirculation was studied by laser Doppler flowmetry with a LAKK-02 apparatus (Lazma, Russia). CP patients had heterogeneous microcirculation with a significantly increased frequency of its pathologic types (spastic, hyperemic, spastic-congestive). Major characteristics of microcirculation were significantly different from those in healthy subjects. Combination of drug therapy and LILT substantially improved microcirculation regardless of its hemodynamic type.

A randomized controlled trial of antioxidant supplementation for pain relief in patients with chronic pancreatitis.

BACKGROUND & AIMS: Oxidative stress has been implicated in the pathophysiology of chronic pancreatitis (CP). We evaluated the effects of antioxidant supplementation on pain relief, oxidative stress, and antioxidant status in patients with CP. METHODS: In a placebo-controlled double blind trial, consecutive patients with CP were randomized to groups that were given placebo or antioxidants for 6 months. The primary outcome measure was pain relief, and secondary outcome measures were analgesic requirements, hospitalization, and markers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant status (ferric-reducing ability of plasma [FRAP]). RESULTS: Patients (age 30.5+/-10.5 years, 86 male, 35 alcoholic, and 92 with idiopathic CP) were assigned to the placebo (n=56) or antioxidant groups (n=71). After 6 months, the reduction in the number of painful days per month was significantly higher in the antioxidant group compared with the placebo group (7.4+/-6.8 vs 3.2+/-4, respectively; P< .001; 95% CI, 2.07, 6.23). The reduction in the number of analgesic tablets per month was also higher in the antioxidant group (10.5+/-11.8 vs 4.4+/-5.8 respectively; P= .001; 95% CI, 2.65, 9.65). Furthermore, 32% and 13% of patients became pain free in the antioxidant and placebo groups, respectively (P= .009). The reduction in the level of TBARS and increase in FRAP were significantly higher in the antioxidant group compared with the placebo group (TBARS: placebo 1.2+/-2.7 vs antioxidant 3.5+/-3.4 nmol/mL; P= .001; 95% CI 0.96, 3.55; FRAP: placebo -5.6+/-154.9 vs antioxidant 97.8+/-134.9 microMFe(+2) liberated, P= .001, 95% CI 44.98, 161.7). CONCLUSIONS: Antioxidant supplementation was effective in relieving pain and reducing levels of oxidative stress in patients with CP.

[Nutritional repercussions and management of chronic pancreatitis]. / Repercusiones nutricionales y manejo de la pancreatitis crónica.

The pancreas is a retroperitoneal organ that releases water, bicarbonate and digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and, less frequently hypertriglyceridemia, primary hyperparathyroidism or cystic fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP principally involves management of pain. A significant change in the pain pattern or the sudden onset of persistent symptoms suggests the need to rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then is important to establish a secure diagnosis. Management of pain should then proceed in a judicious stepwise approach avoiding opioids dependence. Patients should be advised to stop alcohol intake. Fat malabsorption and other complications may also arise. Management of steatorrhea should begin with small meals and restriction in fat intake. Pancreatic enzyme supplements can relieve symptoms and reduce malabsorption in patients who do not respond to dietary restriction. Enzymes at high doses should be used with meals. Treatment with acid suppression to reduce inactivation of the enzymes from gastric acid are recommended. Supplementation with medium chain triglycerides and fat soluble vitamin replacement may be required. Management of other complications (such as pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis and pseudoaneurysms) often requires aggressive approach with the patient kept on total parenteral nutrition to minimize pancreatic stimulation.

Physiological evaluation of the severity of pancreatic exocrine dysfunction during endoscopy.

OBJECTIVES: Despite the advances in pancreatic imaging, there continues to be a need to measure exocrine function to determine which patient requires enzyme supplementation. To evaluate the potential use of a rapid endoscopic test that can be conducted by nonacademic centers, we investigated whether concentration of trypsin in food-stimulated secretion is related to trypsin synthesis and secretion. METHODS: Subjects include 22 chronic pancreatitis patients (10 mild, 5 moderate, and 7 severe radiological disease) and 11 healthy controls. During upper gastrointestinal endoscopy, pancreatic secretion was stimulated by a single 30-mL duodenal injection of an enteral diet, followed 5 minutes later by periampullary juice aspiration (endoscopic pancreatic function test [ePFT]). This was followed by a conventional 2-hour marker-perfusion diet-stimulated pancreatic trypsin secretion and synthesis study (2-hour PFT [2hPFT]). RESULTS: Severity of radiological disease was associated with a progressive loss of enzyme secretion measured by the 2hPFT. The endoscopic PFT correlated positively with 2hPFT (r2 = 0.48; P < 0.0001) and an activity of less than 5% of the average normal had a 96% specificity and 75% sensitivity for the detection of pancreatic insufficiency as defined by a loss of greater than 90% of pancreatic secretion. CONCLUSIONS: The diagnostic power of endoscopy may be enhanced by the collection of a pancreatic juice sample after enteral feed stimulation because measurement of the trypsin content will identify chronic pancreatitis patients who will be benefited by enzyme supplementation.