The Variability of Tryptophan Metabolism in Patients with Mixed Type of Irritable Bowel Syndrome.

Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms.

Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study.

BACKGROUND: Vedolizumab is recommended as a first-line biological treatment, along with other biological drugs, in ulcerative colitis (UC) patients in whom conventional therapy failed and as a second-line biological treatment following a failure of a tumor necrosis factor alpha (TNF-α) antagonist. OBJECTIVES: We aimed to assess the real-world effectiveness and safety of vedolizumab induction therapy in UC patients treated in the scope of the National Drug Program (NDP) in Poland. MATERIAL AND METHODS: The endpoints were the proportions of patients who reached clinical response, clinical remission and mucosal healing at week 14. Partial Mayo scores, Mayo subscores and C-reactive protein (CRP) levels were also evaluated. RESULTS: Our study population consisted of 100 patients (55 biologic-naïve and 45 biologic-exposed). The median total Mayo score at baseline was 10 (interquartile range (IQR): 9-11), and 52 patients (52%) had extensive colitis. The clinical response at week 14 was achieved in 83 (83%) and clinical remission in 24 (24%) cases. Mucosal healing was observed in 56 (62%) patients at week 14. In patients with prior failure of biologic treatment (n = 25), 17 (68%) responded to vedolizumab treatment. A decrease in the median CRP level (from 3.7 mg/L to 2.6 mg/L) and the median total Mayo score (from 10 to 4) was observed. No new safety concerns were recorded and no patients discontinued the treatment due to adverse events (AEs). CONCLUSIONS: Vedolizumab was effective and safe as induction therapy for UC in a Polish real-world population including patients with severely active UC and a low number of patients with prior biological treatment failures.

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease. Objectives: We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland. Design: This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019. Methods: The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment. Results: In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years. Conclusion: Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high. Registration: ENCePP (EUPAS34119).

Effects of Microencapsulated Sodium Butyrate, Probiotics and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome: A Study Protocol of a Randomized Double-Blind Placebo-Controlled Trial.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease in the pathogenesis of which gut dysbiosis may play an important role. Thus, probiotics, prebiotics, or microbiota metabolites, such as butyric acid, are considered to be effective therapy for IBS. However, there are still no trials presenting the efficacy of these three biotic components administered simultaneously. This study aims to evaluate the effects of the product comprising sodium butyrate, probiotics, and short-chain fructooligosaccharides (scFOS) on the severity of clinical IBS symptoms and the quality of life (IBS-QOL). This is a randomized double-blind placebo-controlled trial conducted in 120 adults with IBS diagnosed according to Rome IV criteria. The intervention group (n = 60) will receive a mixture of the following components: 300 mg of colon-targeted microencapsulated sodium butyrate combined with probiotic Lactobacillus strains (L. rhamnosus and L. acidophilus) and Bifidobacterium strains (B. longum, B. bifidum, B. lactis), and 64 mg of prebiotic scFOS. The control group (n = 60) will receive a placebo (maltodextrin). The primary outcomes will be changes in IBS symptoms with the use of the IBS-Severity Scoring System (IBS-SSS), IBS-Global Improvement Scale (IBS-GIS), IBS-Adequate Relief (IBS-AR), and IBS-QOL after 12 weeks of intervention. The secondary outcomes will be the type of stools, patient-recorded symptoms, adverse events, anthropometric and nutritional parameters, and inflammatory cytokine levels. The findings will provide the first evidence of the use of a combination of three biotic compounds in IBS. The study was registered in the clinicaltrials.gov registry under the number NCT05013060.

The role of serotonin in pathogenesis of unclassified irritable bowel syndrome.

The pathogenesis of irritable bowel syndrome (IBS) has not been clearly understood. Numerous factors, including neurotransmitters, can interfere with the functions of the digestive tract. AIM: The aim of present study was to determine the secretion and metabolism of serotonin in patients with unclassified irritable bowel syndrome (IBS-U). MATERIALS AND METHODS: The study included 50 healthy subjects (Controls) and 50 patients with IBS-U, diagnosed according to Rome IV Criteria of functional gastrointestinal disorders. The severity of gastrointestinal symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS- IBS). The quality of sleep was estimated by Insomnia Severity Index (ISI). The serum serotonin and melatonin levels and 5-hydroxyindoleacetic acid (5-HIAA) and 6-sulfatoxymelatonin (aMT6s) concentration in urine were determined with ELISA method. RESULTS: Compared to control group, patients with IBS-U had a higher serum levels (201.3 ± 37.8 vs 145.4 ± 36.9 ng/ml, p < 0.001) and lower levels of melatonin (5.86 ± 1,16 vs9.11 ±2.43 pg/ml, p < 0.001). Likewise, in IBS-U patients urinary excretion of 5-HIAA was greater, while aMT6s excretion was lower. Due to the above changes cyproheptadine (6 mg daily) or melatonin (7 mg daily) was recommended to be taken. After 12 weeks of taking cyproheptadine, the IBS symptoms disappeared in 86.6% patients, and in 20.0% of those taking melatonin. Both drugs improved sleep in equal measure. CONCLUSIONS: Increased serotonin secretion may be the cause of abdominal complaints in unclassified irritable bowel syndrome, what should be considered in its treatment.

Altered tryptophan metabolism in patients with recurrent functional abdominal pain.

The causes of functional abdominal pain are still unclear. The role of food factors in their pathogenesis has been assessed by many researches, but the obtained results are varied. AIM: The aim of present study was to evaluate metabolism of tryptophan, which is substrate for serotonin synthesis and other bioactive compounds, in patients with recurrent functional abdominal pain. MATERIALS AND METHODS: Thirty patients with recurrent abdominal pain and 30 healthy subjects were enrolled in this study. Urinary levels of tryptophan (TRP), 5-hydroxyindoleacetic acid(5-HIAA), L-kynurenine (KYN), xanthurenic acid(XA), and quinolinic acid(QA) were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS), and related to creatinine level (mg/gCr), during active phase(day with acute pain), and silence period, which recommended optimalisation of tryptophan intake. RESULTS: 5-HIAA/TRP ratio and KYN/TRP ratio as well as QA level s were significantly higher in patients compared to control group (p<0.001). After reducing TRP consumption, the above results improved, in particular, the level of QA decreased from 6.88±1.04 mg/Cr to 4,32±0.97 mg/gCr (p<0.001). CONCLUSIONS: Altered tryptophan metabolism may affect locally-andcentrally mediated recurrent functional abdominal pain.

Characteristics of patients with moderate-to-severe ulcerative colitis treated with vedolizumab: results from a Polish multicenter, prospective, observational real-life study (the POLONEZ study).

BACKGROUND: Vedolizumab, a humanized antibody targeting the α4ß7 integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients. METHODS: This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score. RESULTS: A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups. CONCLUSIONS: Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119). LAY SUMMARY: Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.

Social Distancing during COVID-19 Pandemic among Inflammatory Bowel Disease Patients.

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study included 473 patients with IBD who made 1180 hospital visits from 1 May to 30 September 2020. During each visit, the patients completed a five-step, progressive scale that was developed to assess the degree of social isolation. In parallel, other demographic data were collected and the concentrations of anti-severe acute respiratory coronavirus 2 (SARS-CoV-2) IgG and IgM+IgA antibodies were measured using the ELISA method. (3) Results: The study found a significant correlation between the degree of social distancing and the presence of anti-SARS-CoV-2 antibodies in the groups with the lowest degree of isolation (3 to 5). (4) Conclusions: Maintaining social distancing is an effective method for reducing the spread of SARS-CoV-2 virus among IBD patients.

[The role of intraepithelial lymphocytes in pathogenesis of small intestinal bacterial overgrowth syndrome]. / Rola limfocytów sródnablonkowych w patogenezie zespolu przerostu bakteryjnego jelita cienkiego.

Small intestinal bacterial overgrowth (SIBO) is a frequent cause of chronic abdominal complaints. So far, a lot information has been gathered on its pathogenesis but are still doubts that raise question why its causes chronic diarrhea in some and constipation in other patients. AIM: The aim of the study was to assess the number of endothelial lymphocytes (IELs) in the duodenal and ileum mucosa in patients with SIBO with dominant diarrhea (SIBO-D) and dominant constipation (SIBO-C). MATERIALS AND METHODS: The study was performed in 30 healthy patients (group I) and 40 patients with SIBO and diarrhoea (group II), and in 4o patients with constipation (group III). To diagnose SIBO the lactulose hydrogen breath test (LHBT) was performed. To determine the number of intraepithelial lymphocytes in duodenal and jejunal mucosa the histological assessment was performed using haematoxylin-eosin staining. Moreover, immunochistochemical method was used to assess the number of enterochromatoffin cells (EC, chromogranin A - LK-2H10) in these some parts of the gut. RESULTS: The results of LHBT were similar in group II and III - 75,6±18,1 ppm and 66,9±16,2 ppm(p>0,05). The number of IELs in duodenal mucosa in controls was 14,6±4,1/100 EN, in group II - 28,3±6,8/100 EN (p<0.01), and in group III - 23,0±9,9/100 EN (p<0,05), and similar differences were in jejunal mucosa. The number of EC in both parts of the gut was higher in SIBO compared to controls. Furthermore, in patients with SIBO-D the number of IELs in duodenum, as well as in jejunum, was positively correlated with the number of EC cells ( p<0,05, p=0,056, respectively). CONCLUSIONS: In patients with SIBO, particularly with SIBO-D, increased number of IELs I EC cells may be a cause of diverse abdominal symptoms.

Diagnostic and therapeutic recommendations in pancreatic ductal adenocarcinoma. Recommendations of the Working Group of the Polish Pancreatic Club.

These recommendations refer to the current management in pancreatic ductal adenocarcinoma (PDAC), a neoplasia characterised by an aggressive course and extremely poor prognosis. The recommendations regard diagnosis, surgical, adjuvant and palliative treatment, with consideration given to endoscopic and surgical methods. A vast majority of the statements are based on data obtained in clinical studies and experts' recommendations on PDAC management, including the following guidelines: International Association of Pancreatology/European Pancreatic Club (IAP/EPC), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN) and Polish Society of Gastroenterology (PSG) and The National Institute for Health and Care Excellence (NICE). All recommendations were voted on by members of the Working Group of the Polish Pancreatic Club. Results of the voting and brief comments are provided with each recommendation.

Therapeutic efficacy of amoxicillin and rifaximin in patients with small intestinal bacterial overgrowth and Helicobacter pylori infection.

INTRODUCTION: Small intestinal bacterial overgrowth (SIBO) may coexist with Helicobacter pylori infection, which can be the cause of chronic gastrointestinal complaints. AIM: Evaluation of the therapeutic efficacy of amoxicillin and rifaximin in the treatment of these diseases. MATERIAL AND METHODS: The lactulose hydrogen breath test (LHBT) and the urea breath test (13C-UBT) were performed in 116 patients. In 62 patients the coexistence of small intestinal bacterial overgrowth and H. pylori infection was observed. Then, in group I (n = 30) pantoprazole (2 × 40 mg), amoxicillin (2 × 1000 mg) and metronidazole (2 × 500 mg) and in group II (n = 32) pantoprazole and amoxicillin at the above doses and rifaximin (3 × 400 mg) were administered for 10 days. After 6 weeks, both breath tests were repeated and the degree of remission of symptoms was measured using a 10-point visual analog scale (VAS). RESULTS: After the treatment the LHBT index decreased in group I from 61.2 ±19.4 ppm to 22.0 ±8.2 ppm (p < 0.001) and in group II from 59.6 ±15.5 ppm to 15.2 ±8.6 ppm (p < 0.001). Eradication of H. pylori (13C-UBT below 4.0‰) was achieved in 63.3% of patients in group I and 59.4% in group II (p > 0.05). The decrease of pain below 3.0 points in the VAS was obtained in 64.8% of patients in group I and in 56.2% in group II. CONCLUSIONS: Combination of amoxicillin and rifaximin may be effective in the treatment of patients with small intestinal bacterial overgrowth syndrome and concomitant H. pylori infection.

Vitamins D and K as Factors Associated with Osteopathy in Chronic Pancreatitis: A Prospective Multicentre Study (P-BONE Study).

BACKGROUND: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies carry several limitations. Vitamin K is essential for bone metabolism, but its role in this setting has never been investigated. Our aim is to assess the prevalence of osteoporosis and osteopenia in CP patients, and to investigate the association between osteopathy and CP features and nutritional parameters, especially vitamin D and K levels. METHODS: Multicentre cross-sectional study on CP patients diagnosed according to M-ANNHEIM criteria. Bone density was evaluated by dual-energy X-ray absorptiometry and pancreatic function by faecal elastase. Nutritional evaluation included vitamin D and vitamin K. Differences between patients with or without osteopathy were evaluated. The association between investigated variables and bone density were analysed with logistic regression analysis. RESULTS: In total, 211 CP patients were enrolled at eight Centres (67% men; mean age 60). In total, 18% had advanced-marked CP, 56% suffered from pancreatic exocrine insufficiency and disease aetiology was alcoholic in 43%. Vitamin D and K were deficient in 56% and 32%, respectively. Osteopenia was diagnosed in 42% and osteoporosis in 22%. In the multivariate analysis, female sex (OR 2.78), age (OR 1.07 per year) and higher BMI (OR 0.84) were associated with the presence of osteoporosis. In male patients, the only factor associated with osteoporosis was vitamin K deficiency (OR 4.23). CONCLUSION: The present data confirm a high rate of osteopathy in CP patients and highlight the relevance of vitamin K deficiency as only factor associated with osteoporosis in male patients for the first time.

[Thyroid dysfunction in patients with small intestinal bacterial overgrowth]. / Ocena czynnosci tarczycy u osób z zespolem przerostu bakteryjnego jelita cienkiego.

Small intestinal bacterial overgrowth (SIBO), similarly as thyroid diseases, is characterized by chronic diarrhea or constipation, but it is not known whether there is a causal relationship between these disorders. AIM: The aim of the study was to assess thyroid function indices in different clinical forms of SIBO. MATERIALS AND METHODS: The study was performed in 34 patients with diarrhea predominant SIBO (group I), 30 with constipation predominant SIBO (group II) and 30 clinically healthy subjects (control group - K). Small intestinal bacterial overgrowth was assessed with lactulose hydrogen breath test (LHBT) using the breath-hydrogen analyzer (Gastrolyser, Bedfont). Serum thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels were determined by immunochemical method (ELFA) and anti-thyroid peroxidase (ATPO) protein level by immunoenzymatic method (ELISA). RESULTS: LHBT value was respectively in groups: K - 8,5 ± 2,9 ppm, I - 66,9 ± 16,9 ppm, II- 62,0 ± 15,5 ppm (p <0,001). The levels of hormones were similar in group K and I, whereas in group II differentiated: FSH 2,5 ± 0,7 vs. 3,8 ± 1,8 mU/L (p <0,05), FT3- 5,1 ± 1,2 vs. 3,7 ± 1,0 mU/L (p <0,05), FT4 - 14,1 ± 2,5 vs. 9,4 mU/L (p <0,01). In both groups of patients the levels of ATPO were statistically significantly higher than in the control group - respectively: K - 6,3 ± 3,1 IU/ml , I - 39,9 ± 23,4 IU/ml (p < 0,001), II - 94,1 ± 56,3 IU/ml (p <0,001). CONCLUSIONS: Thyroid function may be impaired in patients with small intestinal bacterial overgrowth which should be taken into account in the diagnostic and therapeutic management of the diseases of these organs.

Deficiency of fat-soluble vitamins in chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic pancreatitis (CP) patients are at risk for fat-soluble vitamins (A, D, E, K) deficiency, but available studies are small and heterogeneous. We conducted a systematic review and meta-analysis to determine the prevalence of fat-soluble vitamins deficiency in CP patients. METHODS: Medline was searched up to January 2016 for case series and case-control studies reporting prevalence of fat-soluble vitamin deficiency in CP patients. The prevalent deficiency rate was pooled for included studies, and deficiency rate between CP and controls, with relative odds ratio (OR) and 95% confidence interval (CI) calculated for case-control studies. RESULTS: Twelve studies including 548 patients included. With a random-effect model, the pooled prevalence rate of vitamin A, D and E deficiency were 16.8% (95%CI 6.9-35.7), 57.6% (95%CI 43.9-70.4) and 29.2% (95%CI 8.6-64.5) respectively, with considerable heterogeneity (I2 = 75%, 87.1% and 92%). Only one study evaluated vitamin K deficiency. The pooled OR for vitamin D deficiency in CP cases compared with controls was 1.17 (95% CI 0.77-1.78). Sensitivity analyses showed lower prevalence of vitamin A and E, and higher prevalence of vitamin D deficiency in high-quality studies. The rate of pancreatic exocrine insufficiency did not seem affect the deficiency rates, while the use of different cut-offs influences results and heterogeneity for vitamin E, but not A. CONCLUSIONS: Fat-soluble vitamins deficiency is frequent in CP patients, with considerable heterogeneity. There is, however, no apparent increased risk of vitamin D deficiency in CP compared to controls. Larger, high-quality studies are necessary to better estimate the prevalence of fat-soluble vitamins deficiency, including vitamin K.

Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma.

AIM: To estimate the levels of serum cytokines in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) patients in order to evaluate their usefulness as possible biomarkers. METHODS: The study included 167 Caucasian patients: 74 with PDAC (28 men and 42 women, aged 30-88 years), 78 with CP (50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor (TGF)-ß1, HA and s-Fr were measured in patients with CP (n = 78), PDAC (n = 74) and healthy controls (n = 15) using ELISA (Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification. RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-ß1 serum level (1066 ± 582 and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr (2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA (199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course (2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-ß1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-ß1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group (986 vs 839, P = 0.043). CONCLUSION: Serum TGF-ß1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-ß1 may be useful to predict endocrine insufficiency in PDAC.

Insulinoma--rare, but important clinical problem. Analysis of a series of 530 patients who underwent surgical treatment for the pancreatic tumor.

UNLABELLED: Insulinomas are rare tumors, accounting for 1-2% of all neoplasms of the pancreas. Usually their treatment is not associated with any problems; however there is a small subset of problematic clinical cases. The authors present their own clinical experience with surgical treatment of insulinomas of the pancreas. The aim of the study was to conduct a retrospective analysis of patients with insulinomas of the pancreas who underwent surgical treatment at Department of General and Transplant Surgery Medical University in Lódz. MATERIAL AND METHODS: The study included all patients who underwent surgical treatment at the Department between 2007 and 2013 for the tumor of the pancreas. Further retrospective analysis included all patients with tumors of the insulinoma type. The data was obtained from medical records, surgical protocols and histopathology reports. RESULTS: The analysis included 530 patients who underwent surgical treatment for the tumor of the pancreas. Insulinoma was found in 10 (1.88%) patients (8 females, 2 males). An average age of patients who underwent surgical treatment was 47.5±13.8 years. An average size of the tumor was 1.6±0.5 cm. Six patients underwent extirpation of the insulinoma, while the other patients underwent distal resection of the pancreas. All patients underwent "an open surgical procedure". The average duration of the surgical procedure was 55±45 minutes. Duration of the hospitalization in the analyzed group of patients was 7±5 days. Incidence of postoperative pancreatic fistulas was 10%. All insulinomas were benign. CONCLUSIONS: Insulinomas were rare among patients who underwent surgical treatment at the Department. They were benign and their treatment was unproblematic. However, there is a small group of cases that can be associated with problematic clinical situations. Thus treatment of patients with insulinomas should be conducted at specialist centers. Correct diagnostic and therapeutic management, involving close cooperation between multiple medical specialists, results in complete curing of majority of patients.

Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer.

INTRODUCTION: Some authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency. AIMS: We evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed. METHODS: The pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m(2)) with newly diagnosed PC (within last 1-3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation). RESULTS: Patients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p < 0,0008). In contrast PC patients showed more than six fold higher level of resistin (126.2 ± 143.2 vs 18.9 ± 7.2 ng/mL; p < 0.009) than controls. The median plasma visfatin was 2.8 ± 1.8 ng/mL, which was not significantly different from the controls (3.8 ± 1.1 ng/mL). When PC patients with and without diabetes were considered separately, plasma leptin concentrations among nondiabetic patients were slightly, but not significantly higher (44.6 ± 21.0) as compared to diabetics (34.5 ± 20.7). Moreover there was no difference between visfatin and resistin level in PC, among patients with and without diabetes. No significant differences between serum level of leptin, visfatin and resistin and age, gender, BMI, smoking status, tumor localization, distant metastases and pain has been found. CONCLUSION: The results of this study confirm previous findings that patients with newly diagnosed pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders.

[Serum concentration of insulin, C-peptide and insulin-like growth factor I in patients with colon adenomas and colorectal cancer]. / Stezenie insuliny, C-peptydu i insulinopodobnego czynnika wzrostu I w surowicy chorych z polipami i rakiem jelita grubego.

UNLABELLED: Colon carcinogenesis is a multi-steps process in which many growth factors are involved. In some studies the increased risk of colon cancer development was observed in patients with diabetes mellitus type 2 with accompanying hyperinsulinemia. It is also known that insulin-like growth factor I (IGF-I) plays an important role in proliferation, growth, differentiation and inhibiting apoptosis of both epithelial and carcinoma cells. The aim of the study was to evaluate the serum concentration of insulin, C-peptide and IGF-I in patients with colon adenomas and colorectal cancer. MATERIALS AND METHODS: In 17 patients with colon cancer, 32 patients with colon adenomas and in 12 healthy persons the serum concentration of insulin, C-peptide and IGF-I was determined using ELISA kits. RESULTS: In patients with colon cancer significantly higher serum IGF-I concentration comparing to the control group was observed (85.66 ng/ml vs. 60.96 ng/ml; p < 0.05). Higher IGF-I concentration was also observed in patients with distal tumors comparing to the proximal localisation (95.40 ng/ml vs. 64,65 ng/ml, p < 0.05) and in more differentiated tumors (84.36 ng/ml vs. 75.24 ng/ml). Similarly, higher C-peptide concentrations were observed in distal tumors (635.64 pmol/ I vs. 578.69 pmol/l) and in well-differentiated carcinoma (671.32 pmol/ I vs. 575.66 pmol/l). In patients with colon adenomatous polyps we also observed higher serum IGF-I concentrations I comparing to the control group (82.1 ng/ml vs. 60.96 ng/ml), in high dysplasia adenomas (84.12 ng/ml vs. 79.67 ng/ml) and in smaller adenomas to 1 cm diameter (97.98 ng/ml vs. 73.28 ng/ml), but the differences were not significant. We also observed higher concentration of C-peptide in patients with low grade dysplasia adenomas (665.24 pmol/l vs. 498.13 pmol/l) and with small polyps (611.51 pmol/l vs. 514.89 pmol/l). There were no differences in serum concentration of IGF-I and C-peptide between patients with tubular and villous adenomas. There was no statistical difference observed in insulin serum concentration in all groups of patients. CONCLUSIONS: IGF-I is probably involved particularly in the early stage of colon carcinogenesis.