Michał Drews

Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients

IntroductionThe aim of the study was to describe the levels of circulating monocyte/macrophage pro-inflammatory cytokines (TNF-α, IL-1β IL-6, and IL-8) and an anti-inflammatory cytokine (IL-10) in inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients and healthy controls.Materials and MethodsThe study was conducted on 15 healthy individuals, 20 patients with ulcerative colitis (UC), 12 with Crohn’s disease (CD), and 15 with CRC (Dukes’ stage B). Blood serum cytokine levels were measured by ELISA.ResultsThe patients with UC had significantly higher levels of the pro-inflammatory cytokines and of circulating IL-10 than the healthy controls. The patients with CD and CRC had the same specific pattern of serum cytokines of significantly elevated levels of the pro-inflammatory cytokines, but the IL-10 levels were within the range found in the healthy individuals.ConclusionsThus our results demonstrate that both IBD and CRC are linked with an intensified production of a wide array of monocyte/macrophage pro-inflammatory cytokines which is not accompanied by elevated levels of circulating IL-10, except for its insufficiently inhibitory elevation in UC patients.

Natural Killer Cell Cytotoxicity and Immunosuppressive Cytokines (IL-10, TGF-β1) in Patients with Gastric Cancer

Cytotoxic activity of NK cells was estimated as related to IL-10 and TGF-β1 serum levels and Helicobacter pylori infection in gastric cancer patients. Moreover, we sought to determine whether human gastric adenocarcinoma cells in vitro release IL-10, TGF-β1 or factor(s) affecting NK cytotoxicity. The studies were conducted on 42 patients with gastric cancer (14 with I-II stage—group 1; 28 with III-IV stage—group 2) and on 20 healthy volunteers. The cytotoxicity was tested on NK cells isolated from peripheral blood. IL-10 and TGF-β1 levels were determined by ELISA. H. pylori was detected in cultures of gastric mucosa biopsies and in direct preparations. In 71.4% patients of group 1 NK cytotoxicity and IL-10 serum levels remained within a normal range while in 68% patients of group 2 a marked decrease was noted in cytotoxic function of NK cells, accompanied by increased levels of IL-10 in serum. In turn, in most patients of either group, independently of NK cytotoxicity and stage grouping in the patients, elevated serum levels of TGF-β1 were detected. Presence of H. pylori infection manifested no relationship with NK cytotoxicity, IL-10, or the TGF-β1 serum levels. In cultures of tumour cells presence of IL-10 and TGF-β1 was demonstrated. Nevertheless, supernatants of the cultures did not change cytotoxic activity of NK cells. Development of gastric carcinoma is accompanied by markedly decreased cytotoxic function of NK cells and by elevated IL-10 and TGF-β1 serum levels. Gastric carcinoma cells may release IL-10, the suppressive activity of which may in a secondary manner decrease NK cytotoxicity.

Fecal pyruvate kinase (M2-PK): A new predictor for inflammation and severity of pouchitis

A dimeric isoform of pyruvate kinase (TuM2-PK) in stool has been suggested as a useful screening marker for gastrointestinal cancers with 73% sensitivity and 78% specificity [1]. Pyruvate kinase is a ubiquitous enzyme present in virtually all prokaryotic and eukaryotic cells catalyzing the regulatory step in the glycolytic pathway, the conversion of phosphoenolpyruvate (PEP) to pyruvate. Pyruvate kinase exists in two different isotypes: its tetrameric form (M1) has been found in skeletal muscles, heart and brain, whereas the dimeric form (M2) is present in undifferentiated and proliferating tissues [2]. Increased TuM2-PK concentration in polymorphonuclear neutrophils was documented in patients with polytrauma [3] and chronic cardiac failure [4]. We therefore investigated whether this stool test could be used to detect intestinal inflammation in a diagnostically challenging disease in which for the test period we could rule out any tumor involvement.

Adjuvant Chemotherapy with Etoposide, Adriamycin and Cisplatin Compared with Surgery Alone in the Treatment of Gastric Cancer: A Phase III Randomized, Multicenter, Clinical Trial

Objective: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide, Adriamycin and cisplatin (EAP) after potentially curative resections for gastric cancer. Methods: After surgery, patients were randomly assigned to the EAP or control arm. Chemotherapy included 3 courses, administered every 28 days. Each cycle consisted of doxorubicin (20 mg/m2) on days 1 and 7, cisplatin (40 mg/m2) on days 2 and 8, and etoposide (120 mg/m2) on days 4, 5, and 6. Results: Of 309 eligible patients, 141 were allocated to chemotherapy and 154 to the supportive care group. Four (2.8%) treatment-related deaths were recorded, including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure. Grade 3 or 4 toxicities were found in 17 (22%) patients. According to the intention-to-treat analysis, the median survival was 41.3 months (95% confidence interval, 24.5–58.2) and 35.9 months (95% confidence interval, 25.5–46.3) in the chemotherapy and control group, respectively (p = 0.398). Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7–15 metastatic lymph nodes. Conclusion: Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients.

Decreased expression of ten-eleven translocation 1 protein is associated with some clinicopathological features in gastric cancer.

A decrease in ten-eleven translocation 1 (TET1) transcript and 5-Hydroxymethylcytosine (5hmC) levels has recently been demonstrated in primary gastric cancer (GC). However, little is known about TET1 protein levels in gastric tumoral and nontumoral tissue. Therefore, using reverse transcription, real-time quantitative polymerase chain reaction and western blotting analysis, we determined the TET1 transcript and protein levels in tumoral and nontumoral tissue from 38 patients with GC. We also assessed the association between the decrease in TET1 transcript and protein levels and some clinicopathological features in primary GC. We found significantly decreased levels of TET1 transcript (P=0.0023) and protein (P=0.00024) in primary tumoral tissues as compared to nontumoral tissues in patients with GC. Moreover, we also observed significantly lower amounts of TET1 transcript (P=0.03) and protein (P=0.00018) in tumoral tissues in patients aged>60. We also found significant lowered TET1 protein levels in male patients (P=0.0014), stomach (P=0.044) and cardia (P=0.013) tumor localization, T3 depth of invasion (P=0.019), N1 (P=0.012) and N3 lymph node metastasis (P=0.013) and G3 histological grade (P=0.0012). There were also significant decreases in TET1 transcript levels in female patients (P=0.042), intestinal histological types (P=0.0079) and T4 depth of invasion (P=0.037). Our results demonstrated that a decrease in TET1 transcript and protein levels is associated with some clinicopathological features in GC.

Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome

Aim  Abdominal pain, defaecation disorder and change of bowel habit are the commonest symptoms of irritable bowel syndrome (IBS). The effect of microencapsulated sodium butyrate (MSB) was assessed on the severity of symptoms in patients with IBS.

Pouchitis may increase the risk of dysplasia after restorative proctocolectomy in patients with ulcerative colitis.

Aim  Dysplasia of the pouch mucosa after restorative proctocolectomy is rare. The aim of this study was to establish whether there is a correlation between pouchitis and dysplasia.

Chronic pouchitis is not related to small intestine bacterial overgrowth.

Background: Restorative ileal pouch‐anal anastomosis (IPAA) potentially may lead to upper gastrointestinal tract motility disturbances. In addition, a bacterial etiology of IPAA complication—pouchitis—has been suggested. The oro‐anal transit time is significantly reduced in this patient group. Therefore, we investigated the hypothesis if IPAA constitutes a significant risk for small intestine bacterial overgrowth (SIBO). Methods: Twenty‐eight patients age 23–71 years with IPAA operated due to ulcerative colitis without subjective symptoms of pouchitis were evaluated as outpatients according to the prescheduled follow‐up after operation and included in the study. The modified Pouchitis Disease Activity Index (PDAI) was determined in all IPAA patients, including clinical, endoscopic, and histopathological (Moskowitz criteria) parameters. In addition, anorectal manometry was performed. The presence of SIBO was determined with the use of a glucose breath test (GBT). Results: In 1 subject (3.6%) an abnormal GBT result was recorded consistent with SIBO. In addition, 2 borderline values (7.1%) were documented. Both patients with SIBO as subjects with borderline values presented with low PDAI values. All patients with PDAI >7 had normal GBT results. In patients with SIBO the maximal tolerated rectal volume was significantly higher than in subjects without SIBO (P < 0.007). Similarly, the PDAI value was significantly lower (P < 0.014). Conclusions: Asymptomatic chronic pouchitis is not related to SIBO. However, excessive colonization of the small intestine does occur in some IPAA patients and needs to be kept in the differential diagnosis.

Management of enteroatmospheric fistula with negative pressure wound therapy in open abdomen treatment: a multicentre observational study.

The management of enteroatmospheric fistula (EAF) in open abdomen (OA) therapy is challenging and associated with a high mortality rate. The introduction of negative pressure wound therapy (NPWT) in open abdomen management significantly improved the healing process and increased spontaneous fistula closure. Retrospectively, we analysed 16 patients with a total of 31 enteroatmospheric fistulas in open abdomen management who were treated using NPWT in four referral centres between 2004 and 2014. EAFs were diagnosed based on clinical examination and confirmed with imaging studies and classified into low (<200 ml/day), moderate (200–500 ml/day) and high (>500 ml/day) output fistulas. The study group consisted of five women and 11 men with the mean age of 52·6 years [standard deviation (SD) 11·9]. Since open abdomen management was implemented, the mean number of re‐surgeries was 3·7 (SD 2·2). There were 24 EAFs located in the small bowel, while four were located in the colon. In three patients, EAF occurred at the anastomotic site. Thirteen fistulas were classified as low output (41·9%), two as moderate (6·5%) and 16 as high output fistulas (51·6%). The overall closure rate was 61·3%, with a mean time of 46·7 days (SD 43·4). In the remaining patients in whom fistula closure was not achieved (n = 12), a protruding mucosa was present. Analysing the cycle of negative pressure therapy, we surprisingly found that the spontaneous closure rate was 70% (7 of 10 EAFs) using intermittent setting of negative pressure, whereas in the group of patients treated with continuous pressure, 57% of EAFs closed spontaneously (12 of 21 EAFs). The mean number of NPWT dressing was 9 (SD 3·3; range 4–16). In two patients, we observed new fistulas that appeared during NPWT. Three patients died during therapy as a result of multi‐organ failure. NPWT is a safe and efficient method characterised by a high spontaneous closure rate. However, in patients with mucosal protrusion of the EAFs, spontaneous closure appears to be impossible to achieve.

Vacuum-assisted closure therapy in patients with large postoperative wounds complicated by multiple fistulas

Vacuum-assisted closure (VAC) therapy is a widely acknowledged method for chronic and traumatic wound healing. The feasibility of VAC therapy used for the treatment of intestinal fistulas is still a subject of debate. Complex postoperative wounds pose significant therapeutic problems, especially when there are several fistula openings in the wound area and other sites, usually at the site of previous drains. This paper describes the treatment of three patients in a critical condition, with complex postoperative wounds complicated by multiple fistulas. Vacuum-assisted closure therapy was based on effective drainage of the biggest fistula opening and ensuring conditions promoting the healing process of other fistulas and the wound. A considerable improvement in general condition and wound healing was noted within 2-4 weeks and both the number of fistulas and the volume of excreted contents decreased. After 5-7 weeks a significant improvement in wound healing was observed in all patients. Once the general condition of all patients was considered satisfactory (2-6 months), they underwent surgery aimed at restoration of the digestive tract continuity.In our opinion, VAC therapy used for the treatment of postoperative wounds with multiple fistulas in the wound area and other sites should aim mainly at the improvement of patients’ general condition, limitation of the number of fistulas as well as accelerated wound healing. This may lead to formation of one stoma-type fistula, which can be dressed and cared for by patients until the continuity of the digestive tract has been surgically restored.