Changes in 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D are associated with maturation of regulatory T lymphocytes in patients with chronic pancreatitis: a randomized controlled trial.

OBJECTIVES: We studied the impact of changes in 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) on regulatory T lymphocytes (Tregs) in patients with chronic pancreatitis (CP) and fat malabsorption in a prospective clinical trial. METHODS: The patients were randomized to 1 of 3 treatments during 10 weeks: weekly UV-B in a tanning bed (group A), 1520-IU/d vitamin D supplement (group B), or placebo (group C). A placebo tanning bed was used in groups B and C. We determined the levels of CD4 Tregs (CD3(+)CD4(+)CD25(+)CD127(low)FoxP3(+)) and CD8(+) Tregs (CD3(+)CD8(+)CD25(+)CD127(low)FoxP3(+)), together with 25OHD and 1,25(OH)2D. For baseline comparisons, we included 8 healthy individuals. Of the 30 included patients, 27 (group A, 7 patients; group B, 9 patients; and group C, 11 patients) completed the protocol. RESULTS: The baseline levels of CD4(+) Tregs relative to total CD4(+) count were higher in 22 patients with CP compared with healthy controls (2.8% vs 1.9%, P < 0.05) and were comparable for CD8+ Tregs (0.13% vs 0.05%, P = 0.3). Increases in levels of CD4(+) Tregs correlated to changes in 1,25(OH)(2)D (2% per 100 pmol/L, P = 0.002) and 25OHD (3% per 100 nmol/L, P = 0.01). CONCLUSIONS: Patients with CP have elevated relative levels of CD4(+) Tregs. Increases in 25OHD and 1,25(OH)(2)D were both related with increases in levels of Tregs.

[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.

[Parameters of lipid peroxidation and antioxidative protection in patients with chronic pancreatitis treated by low-intensity laser therapy].

The objective of this study was to evaluate the influence of low-intensity laser therapy (LILT) on the processes of lipid peroxidation (LPO) and antioxidative protection (AOP) in patients with chronic pancreatitis. A total of 78 patients aged from 36 to 77 years were treated with LILT in addition to conventional therapy; the patients of the control group (n = 40) received only medicamentous therapy. Examination of the patients in the exacerbation phase of chronic pancreatitis revealed activation of LPO processes and differently-directed shifts of AOP components. These changes are supposed to reflect variations in the activity of the inflammatory processes in the pancreas and oxidative stress on this organ.

Management of painful chronic pancreatitis with single-dose radiotherapy.

OBJECTIVES: Some patients with chronic pancreatitis present recurrent flare-ups of pancreatitis and/or unrelenting pain. Current management is mostly limited to analgesics and surgery. We reasoned that anti-inflammatory radiotherapy, which has proven useful to alleviate other painful inflammatory painful disorders, might prove valuable for severely symptomatic patients with chronic pancreatitis. METHODS: We prospectively studied the efficacy of single-dose anti-inflammatory radiotherapy in 15 consecutive patients with chronic pancreatitis who fulfilled the following criteria: either two flare-ups of pancreatitis in the previous 6 months and/or continuous pain for more than 3 months. Treatment consisted of a single radiation dose of 8 Gy to the pancreas. Exocrine function (fecal elastase), endocrine function (c peptide), quality of life (EuroQol questionnaire), and clinical outcome were assessed before and after radiation. Response was defined as no further pain or flare-ups of pancreatitis. RESULTS: During follow-up (median: 39 months; range: 4-72 months), 12 patients had no further pain or flare-ups. One patient required a second radiation dose 1 year after the initial treatment, but he has remained well ever since (50 months). Two other patients did not respond to radiotherapy. After radiotherapy either exocrine or endocrine pancreatic function, or both, deteriorated in three patients. Patients who responded to treatment (13/15) gained 4-20 kg in body weight during follow-up (median 4 kg) and EuroQol improved significantly from 0.58 to 0.86 (P<0.001). CONCLUSIONS: Radiotherapy for severe symptomatic chronic pancreatitis appears to be a useful and effective therapeutic choice that could potentially substitute for or delay surgery.

Pancreatitis crónica / Chronic pancreatitis

La etiopatogenia de la pancreatitis crónica no se conoce en profundidad. El hábito de fumar, la autoinmunidad y la presencia de mutaciones en genes específicos se han consolidado como factores etiológicos asociados importantes. La ecoendoscopia, con o sin aspiración-biopsia pancreática, se ha afianzado como una herramienta diagnóstica sensible y específica. En pacientes con pancreatitis crónica, el dolor abdominal puede ser un síntoma invalidante. La radioterapia antiinflamatoria puede mitigar los síntomas y evitar la aplicación de cirugía mutilante. En caso de insuficiencia pancreática, es importante optimizar de forma individual el tratamiento sustitutivo con enzimas pancreáticas. Las pancreatitis autoinmunes están infradiagnosticadas en Europa. El tratamiento con corticoides es muy efectivo, pero su interrupción conduce a recidivas frecuentes. En este contexto, el tratamiento de mantenimiento con azatioprina puede ser de utilidad (AU)

The etiopathogenesis of chronic pancreatitis is not well characterized. Smoking, autoimmunity, and the presence of mutations in specific genes have been demonstrated to be important associated etiological factors. Endoscopic ultrasonography, with or without pancreatic aspiration-biopsy, has good sensitivity and specificity. In patients with chronic pancreatitis, abdominal pain may be a crippling symptom. Antiinflammatory radiotherapy may mitigate the symptoms and avoid the use of mutilating surgery. In pancreatic failure, pancreatic enzyme replacement therapy should be optimized by individualizing the dose. Autoimmune forms of pancreatitis are under-diagnosed in Europe. Corticosteroid therapy is highly effective but its interruption leads to frequent recurrences; in this context maintenance therapy with azathioprine may be useful (AU)

Extrahepatic portal vein occlusion without recurrence after pancreaticoduodenectomy and intraoperative radiation therapy.

PURPOSE: Although there are no definitive studies that characterize the survival benefit of intraoperative radiation therapy (IORT), the therapy does not seem to produce significant complication. In our institution, pancreaticoduodenectomy (PD) and IORT are often complicated by the development of extrahepatic portal vein occlusion (EHPO). The aim of this study was to characterize the phenomenon of EHPO after PD and IORT. METHODS AND MATERIALS: Between September 1992 and December 2001, 107 patients received macroscopic curative PD for periampullary disease in our institution. IORT (radiation dose: 20 Gy) was performed in 53 of these patients. Criteria for diagnosis of EHPO were as follows: (1) computerized tomography findings of occlusive extrahepatic portal vein, (2) symptoms of portal hypertension, and (3) confirmation to exclude tumor recurrence from origin of EHPO, because this study examined whether EHPO was a complication of PD and IORT. RESULTS: EHPO was diagnosed in 12 patients. Among patient and operative variables, IORT was the only statistically significant factor associated with a diagnosis of EHPO (p = 0.0052). The median developed time to EHPO and overall survival after surgery in EHPO patients were 358 days and 2,562 days, respectively. Eight patients (67%) with EHPO died during the follow-up period. At 5 years after therapy, EHPO was diagnosed in 67% of survivors who had received IORT. CONCLUSIONS: Patients undergoing IORT and PD have a relatively high incidence of EHPO, and patients who develop postoperative EHPO have poor prognoses.