Long-Term Functional Outcome After Pancreatoduodenectomy for Periampullary Carcinoma With Morphological Correlation.

OBJECTIVE: The aim of the study was to evaluate the long-term functional outcome (exocrine and endocrine) and morphological changes in remnant pancreas after pancreatoduodenectomy and its clinical impact. METHODS: Periampullary carcinoma patients with minimum follow-up of 2 years and without recurrence were included (N = 102). Exocrine insufficiency includes clinical steatorrhea and fecal elastase-1 (FE-1) levels; endocrine insufficiency, glucose levels and glycated hemoglobin; and morphological changes, main pancreatic duct (MPD) diameter and thickness of remnant pancreas. RESULTS: The mean (standard deviation) follow-up period was 59 (26) months. Of the 102 patients, 81 (80%) had severely deficient FE-1 (0-100 µg/g). The preoperative MPD was significantly more and thickness of remnant pancreas was significantly less in patients with severely deficient FE-1. Overall, 15.6% (16/102) developed steatorrhea and improved on enzyme replacement therapy. The presence of MPD stricture (P = 0.008) and weight loss (P = 0.001) were significantly associated with steatorrhea. New-onset diabetes was seen in 17% (15/90) patients, of whom 3 of 5 developed it after 4 years (range, 4-7 years). The blood glucose was controlled on oral hypoglycemics in 2 (10/15) of 3 patients. CONCLUSIONS: The assessment by FE-1 indicates loss of exocrine function in more than 90%, whereas only 1 of 6 developed steatorrhea and new-onset diabetes. Morphological changes especially MPD stricture affect the functional status of remnant pancreas.

Update on Bile Acid Malabsorption: Finally Ready for Prime Time?

PURPOSE OF REVIEW: To provide an update on the prevalence, pathophysiology, disease associations, and treatment options for bile acid malabsorption (BAM). RECENT FINDINGS: •Molecular mechanisms-BAs prevent water reabsorption and increase water secretion by intracellular mediators, increasing aquaporin channels and intracellular permeability. •Inflammatory bowel disease-new molecular mechanisms of BAM are identified in patients without ileal disease, including changes in expression of ileal BA transporter and nuclear receptors involved in BA homeostasis. •Microscopic colitis-BAM is one of the mechanisms leading to microscopic colitis. •Diagnostic testing-new diagnostic tests have been launched in the USA (serum C4 and fecal 48-h BA excretion); stimulated FGF19 has higher detection of BAM compared to fasting sample alone. •Treatment-investigational FXR agonists may provide a daily, oral option for treatment of BAM instead of BA sequestrants. There is a greater appreciation of the biological role of bile acids across multiple fields of medicine, including gastrointestinal indications.

Negotiating the complexities of exocrine and endocrine dysfunction in chronic pancreatitis.

Chronic pancreatitis is a chronic inflammatory disease of the pancreas characterised by irreversible morphological change and typically causing pain and/or permanent loss of function. This progressive, irreversible disease results in destruction of healthy pancreatic tissue and the development of fibrous scar tissue. Gradual loss of exocrine and endocrine function follows, along with clinical manifestations such as steatorrhoea, abdominal pain and diabetes. Nutrition in chronic pancreatitis has been described as a problem area and, until recently, there was little research on the topic. It is often asserted that >90 % of the pancreas must be damaged before exocrine insufficiency occurs; however, an exploration of the original studies from the 1970s found that the data do not support this assertion. The management of steatorrhoea with pancreatic enzyme replacement therapy is the mainstay of nutritional management, and early identification and treatment is a key. The presence of steatorrhoea, coupled with poor dietary intake (due to intractable abdominal pain, gastrointestinal side effects and often alcoholism) renders the chronic pancreatitis patients at considerable risk for undernutrition, muscle depletion and fat-soluble vitamin deficiency. Premature osteoporosis/osteopenia afflicts two-thirds of patients as a consequence of poor dietary intake of calcium and vitamin D, low physical activity, low sunlight exposure, heavy smoking, as well as chronic low-grade inflammation. Bone metabolism studies show increased bone formation as well as bone resorption in chronic pancreatitis, indicating that bone turnover is abnormally high. Loss of the pancreatic islet cells occurs later in the disease process as the endocrine cells are diffusely distributed throughout the pancreatic parenchyma. Patients may develop type 3c (pancreatogenic) diabetes, which is complicated by concurrent decreased glucagon secretion, and hence an increased risk of hypoglycaemia. Diabetes control is further complicated by poor diet, malabsorption and (for some) alcoholism, and therefore those with type 3c diabetes have clinical characteristics and therapeutic goals that are different from that of type 1 and type 2 diabetes patients. This review describes emerging research and clinical guidelines for nutrition in chronic pancreatitis.

[Structural state of the pancreas and coprogram parameters for assessment patients with chronic pancreatitis after cholecystectomy].

Reviewed by a structural condition of the pancreas by ultrasound and scores from the Marseille-Cambridge classification in patients with chronic biliary pancreatitis, including those who had a history of cholecystectomy. Found that after cholecystectomy gland size decreased slightly, but significantly fibrosis is increased. Chronic inflammation and fibrosis of the gland leads to inhibition of both acinar and ductal secretory function, leads to its external and internal secretion deficiency. In assessing coprogram found that most patients with CP present with signs of exocrine insufficiency, including steatorrhea and kreatorrhea that are most pronounced in patients with CP after open cholecystectomy.

Systematic review: the management of chronic diarrhoea due to bile acid malabsorption.

BACKGROUND: Bile acid malabsorption (BAM) is a common, yet under-recognised, cause of chronic diarrhoea, with limited guidance available on the appropriate management of patients with BAM. AIM: To summarise the evidence supporting different treatments available for patients with bile acid malabsorption, noting their impact on clinical outcomes, tolerability and associated side effects. METHODS: A literature search was conducted through PubMed, the Cochrane Database of Systematic Reviews and Scopus. Relevant articles studied patients who had been diagnosed with BAM and were clinically assessed before and after therapy. RESULTS: A total of 30 relevant publications (1241 adult patients) were identified, which investigated the clinical response to drugs, including colestyramine, colestipol, colesevelam, aluminium hydroxide and obeticholic acid. The most commonly used diagnostic test of bile acid malabsorption was the SeHCAT test (24 studies). Colestyramine treatment was by far the most studied of these agents, and was successful in 70% of 801 patients (range: 63-100%). CONCLUSIONS: Colestyramine and colestipol are generally effective treatments of gastrointestinal symptoms from BAM, but may be poorly tolerated and reduce the bioavailability of co-administered agents. Alternative therapies (including colesevelam and aluminium hydroxide) as well as dietary intervention may also have a role, and the promising results of the first proof-of-concept study of obeticholic acid suggest that its novel approach may have an exciting future in the treatment of this condition. Future trials should employ accurate diagnostic testing and be conducted over longer periods so that the long-term benefits and tolerability of these different approaches can be evaluated.

Steatorrhea and hyperoxaluria occur after gastric bypass surgery in obese rats regardless of dietary fat or oxalate.

PURPOSE: We determined the effect of dietary fat and oxalate on fecal fat excretion and urine parameters in a rat model of Roux-en-Y gastric bypass surgery. MATERIALS AND METHODS: Diet induced obese Sprague-Dawley® rats underwent sham surgery as controls (16), or Roux-en-Y gastric bypass surgery (19). After recovery, rats had free access to a normal calcium, high fat (40%) diet with or without 1.5% potassium oxalate for 5 weeks and then a normal (10%) fat diet for 2 weeks. Stool and urine were collected after each period. Fecal fat was determined by gas chromatography and urine metabolites were evaluated by assay spectrophotometry. RESULTS: Daily fecal fat excretion remained low in controls on either diet. However, Roux-en-Y gastric bypass rats ingested a food quantity similar to that of controls but had eightfold higher fecal fat excretion (p <0.001) and heavier stools (p = 0.02). Compared to controls, gastric bypass rats on the high fat diet with potassium oxalate had a fivefold increase in urine oxalate excretion (p <0.001), while gastric bypass rats without potassium oxalate had a twofold increase in urine calcium (p <0.01). Lowering dietary fat in gastric bypass rats with potassium oxalate led to a 50% decrease in oxalate excretion (p <0.01), a 30% decrease in urine calcium and a 0.3 U increase in urine pH (p <0.001). CONCLUSIONS: In this Roux-en-Y gastric bypass model high fat feeding resulted in steatorrhea, hyperoxaluria and low urine pH, which were partially reversible by lowering the dietary fat and oxalate content. Roux-en-Y gastric bypass rats on normal fat and no oxalate diets excreted twice as much oxalate as age matched, sham operated controls. Although Roux-en-Y gastric bypass hyperoxaluria appears primarily mediated by gut and diet, secondary causes of oxalogenesis from liver or other mechanisms deserve further exploration.

Bleeding tendency in an adolescent with chronic small bowel obstruction.

We report a case of fat-soluble vitamin deficiency in a 14-year old boy who had chronic duodenal obstruction. He presented with periodic unexplained bleeding tendency. The laboratory results showed positive fat globules in stool and prolonged prothrombin time. His further investigation revealed low plasma vitamin A and undetectable plasma vitamin E. After parenteral vitamin K and oral vitamin A and E supplement, these abnormalities resolved although he still had absent knee jerk. We propose that fat malabsorption and fat-soluble vitamin deficiency can occur after prolonged duodenal obstruction that induce bacterial overgrowth following by bile acid deconjugation. Despite very few case reports, screening for fat malabsorption and fat-soluble vitamin deficiency might be warranted in patients with chronic small bowel obstruction.

Late complications after pancreaticoduodenectomy with pancreaticogastrostomy.

INTRODUCTION: We investigated complications after pancreaticoduodenectomy (PD) with pancreaticogastrostomy (PG) reconstruction more than 12 months postoperatively. METHODS: Through chart review and outpatient follow-up, we assessed the incidence of new-onset diabetes mellitus (DM) and steatorrhea after PD. RESULTS: Ninety patients underwent PD with PG with a median follow-up of 4.7 years (range 0.4-15.8 years). Of the 77 patients without DM preoperatively, 18 (23.4%) developed DM postoperatively. Those who developed DM were younger at time of surgery than those who did not (60.5 versus 65.8 years; p = 0.021), but postoperative survival did not differ between these groups. The incidence of DM was comparable to the incidence of DM in the general population. Out of 89 patients, 47 (52.8%) now require pancreatic enzyme therapy. The group that developed steatorrhea underwent PD at a younger age (61.4 versus 67.0 years; p = 0.029). CONCLUSIONS: Patients that undergo PD at a younger age are more likely to develop DM and steatorrhea than their older counterparts; patients are as likely as the general population, however, to develop DM after PD with PG.

[Role of hypophyseal-gonadal system in the genesis of functional pathologies of the digestive system in adolescents].

In different types of functional disorders of the digestive system in adolescents were revealed the same changes of the hormonal state of hypophisial-gonad system. It indicates on dominative role of neuroendocrinal mechanisms in pathogenesis of these diseases.

Biliopancreatic diversion with duodenal switch.

The biliopancreatic diversion with a duodenal switch (BPD-DS) is a less commonly performed but very effective bariatric procedure that has been in existence for more than 20 years. It is particularly effective for the resolution of diabetes and is associated with the highest weight loss among other bariatric operations. Typically, the BPD-DS is not associated with postgastrectomy symptoms, such as dumping and marginal ulceration. Because of its complexity, it has usually been performed by laparotomy in the past; but, more recently, minimally invasive techniques are being used with acceptable risk.

Predictors of osteodystrophy in patients with chronic nonalcoholic pancreatitis with or without diabetes.

OBJECTIVE: To study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables. METHODS: Thirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated. RESULTS: In patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D. CONCLUSION: Pancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC.

La fibrosis quística en la actualidad (I): aspectos digestivos / Cystic fibrosis update time (I): digestive aspects

La fibrosis quística es una enfermedad genética, caracterizada fundamentalmente por neumopatía crónica progresiva e insuficiencia pancreática, pero presenta un amplio espectro de manifestaciones clínicas. En los últimos años se ha profundizado notablemente en su conocimiento y en el desarrollo de nuevas medidas terapéuticas, lo que ha conducido a la prolongación de la expectativa de vida y a una considerable mejora en la calidad de ésta. El pronóstico depende principalmente de la severidad de la afectación pulmonar; sin embargo, controlarlas diversas manifestaciones digestivas y evitar la desnutriciónes esencial para lograr una buena evolución. Los aspectos digestivos son diversos, y en este trabajo se revisan los más recientes tanto desde el punto de vista diagnóstico como terapéutico. La enfermedad hepática, relativamente frecuente, aparece como una complicación temprana; en la mayoría de los casos se desarrolla una afectación leve, aunque una pequeña proporción de pacientes cursan con una alteración severa con cirrosis, que conduce a hipertensión portal e hiperesplenismo. La insuficiencia pancreática exocrina aparece en aproximadamente el 90% de los pacientes, que precisan tratamiento sustitutivo enzimático. Otras complicaciones, como la esteatorrea rebelde, la inflamación intestinal y el síndrome de obstrucción intestinal distal, han adquirido especial relevancia en los últimos años (AU)

Cystic fibrosis is a genetic disorder characterized mainly by a chronic progressive pulmonary disease and pancreatic insufficiency but with a wide range of clinical manifestations. Over the last years breakthroughs in the understanding of its pathogenesis and the development of new therapies have lead to outstanding improvements both in survival and quality of life. Its prognosis mostly depends on the severity of the pulmonary impairment but adequate control of the gastrointestinal manifestations, ensuring a good nutritional condition is essential for achieving a good outcome. The digestive aspects are various and they will be examined from the most recent points of view of therapeutical diagnosis. Liver disease is quite common. It often has an early onset but most patients have competitive lymild impairment with only a few developing multifocal cirrhosis with conducts to a portal hypertension and hypersplenism. Pancreatic exocrine insufficiency occurs in over 90% of the patients and requires of a replacement enzyme therapy. Other complications like unresponsive steatorrhea control, intestinal inflammation and distal intestinal obstruction syndrome have acquired special relevance in the last years (AU)

Determinants of accelerated small intestinal transit in alcohol-related chronic pancreatitis.

Patients with chronic pancreatitis may have abnormal gastrointestinal transit, but the factors underlying these abnormalities are poorly understood. Gastrointestinal transit was assessed, in 40 male outpatients with alcohol-related chronic pancreatitis and 18 controls, by scintigraphy after a liquid meal labeled with (99m)technetium-phytate. Blood and urinary glucose, fecal fat excretion, nutritional status, and cardiovascular autonomic function were determined in all patients. The influence of diabetes mellitus, malabsorption, malnutrition, and autonomic neuropathy on abnormal gastrointestinal transit was assessed by univariate analysis and Bayesian multiple regression analysis. Accelerated gastrointestinal transit was found in 11 patients who showed abnormally rapid arrival of the meal marker to the cecum. Univariate and Bayesian analysis showed that diabetes mellitus and autonomic neuropathy had significant influences on rapid transit, which was not associated with either malabsorption or malnutrition. In conclusion, rapid gastrointestinal transit in patients with alcohol-related chronic pancreatitis is related to diabetes mellitus and autonomic neuropathy.

¿Es la esteatorrea un hallazgo frecuente en pacientes con celiaquia en un hospital de tercer nivel de laciudad de La Paz? / Steatorrhea Is a common finding in patients with celiac disease in a tertiary level city of La Paz?

Pregunta de investigación: Cual será la frecuencia de esteatorrea asociada a celiaquia en pacientes que consultan por diarrea crónica en un Hospital de tercer nivel? Objetivo general: Conocer los aspectos epidemiologicos y clínicos de los pacientes con celiaquia. Objetivos especificos: 1.- Determinar la frecuencia de esteatorrea asociada a enfermedad celiaca.2.- Conocer la correlación del resultado de biopsias del duodeno y las pruebas serológicas especificas de la enfermedad.3.- Determinar la efi cacia del tratamiento dietético en pacientes portadores de esta entidad. Diseño: Serie de casos. Lugar: Instituto de Gastroenterología Boliviano –Japones de la ciudad de La Paz. Participantes Trece pacientes. Metodos: Se estudiaron trece pacientes, ocho mujeres y cinco varones, con un rango de edad de 37 a 68 años. Todos portadores de diarrea crónica.Se les determinó marcadores serológicos específi cos y se les realizó biopsias de duodeno distal. Todos fueron valorados con parâmetros antropométricos al inicio del diagnóstico y seis meses después se correlacionó la respuesta a la dieta sin gluten. Resultados: Los resultados mostraron que la esteatorrea no es el síntoma mas común, los marcadores serológicos de mayor representatividad sonlos anticuerpos antiendomisio y antitransglutaminasa, no así los antigliadina y las biopsias de duodeno demostraron lesiones infiltrativase hiperplasicas, no se evidenció ninguna lesión destructiva. La respuesta a la dieta sin gluten fue en todos los casos favorable y contundente.

Research question: ¿Is the steatorrea the most frecuent sintom in patients with celiac disease at the third level hospital in La Paz city? General objetivs; To identifi ty the epidemiological and clinical caracteristics in patients with celiac disease especific aims: 1.- To identifi ty the esteatorrea frecuency in patients with celiac disease at Instituto de Gastroenterologia Boliviano-Japones in La Paz city. 2.- To establish the correlation betwen the duodenal biopsys and serological test in this illnes.3.- To determine the effectiveness dietoterapic diet in this patients. Desig Serial cases. PlaceInstituto de Gastroenterologia Boliviano Japones at La Paz city. Participants Thirteen patients.Methods: We studied thirteen patients, eight female and fi ve male, 37 to 68 age. All the patients present cronic diarrea. In all we determinate serological marks and duodenal biopsys. We determined antropometric parameters and value the answer the diet without gluten. Results and discusionWe found the esteatorrea isn’t the most sign. The most specifi cal serologycal marks are antiendomisy and antitransglutamins antibodies. Respect to the duodenal biopsys show us infi ltrative and hiperplasic lesions. The diet answer without gluten was in all cases the best answer.

Does the pancreas really produce much more lipase than required for fat digestion?

Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than the very high specific activity usually measured under experimental in vitro conditions which are far from physiological conditions; 4) in patients with reduced human pancreatic lipase secretion, gastric lipase plays a significant role in fat digestion. This last observation might explain the absence of a linear relationship between human pancreatic lipase secretion in chronic pancreatitis and steatorrhea. From the low specific activity displayed by human pancreatic lipase on meal triglycerides, one can better understand why more lipase than expected is needed, why fat digestion lasts for more than a few minutes and, finally, why there is not such an excess secretory capacity for lipase as had been previously thought.

Clinical application of 13C-Hiolein breath test in assessing pancreatic exocrine insufficiency.

OBJECTIVE: To examine the feasibility and significance of 13C-Hiolein breath test in evaluating chronic pancreatitis-related exocrine insufficiency and efficacy of enzyme treatment. METHODS: The 13C-Hiolein breath test was used in 8 healthy volunteers (group 1), 8 chronic pancreatitis (CP) patients without steatorrhea (group 2), and 8 CP patients with steatorrhea (group 3). To evaluate the function of pancreatic exocrine, 13CO2 was determined following 13C-Hiolein diet. The 13C-Hiolein test was repeated in group 3 after enzyme supplement therapy. RESULTS: Administration of 13C-Hiolein diet resulted in significantly higher cumulative percent dose of 13C recovery per 6 h (cPDR/6 h) and maximal PDR (PDR(peak)) in the healthy controls (group 1) than the CP patients with steatorrhea (group 3) (11.22%+/-1.22% and 6.11%+/-0.59% vs 2.87%+/-0.73% and 1.53%+/-0.36%, respectively, both P<0.01). In the CP patients with steatorrhea (group 3), a repeated test after enzyme supplementation therapy showed a significant elevation of both cPDR/6 h and PDR(peak) (9.03%+/-0.84% and 2.33%+/-0.47%, both P<0.01 compared with those before enzyme treatment), but cPDR/6 h remained significantly lower than that in the healthy volunteers (group 1, P<0.05). Both cPDR and PDR(peak) in the CP patients without steatorrhea (group 2) were similar to those in the healthy controls (group 1, both P>0.05). CONCLUSION: The results of 13C-Hiolein breath test well reflect fat metabolism status in CP patients, and the test can be used to monitor the efficacy of pancreatic enzymes therapy.