Maciej Borejsza-Wysocki

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.

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.

Portable VAC therapy improve the results of the treatment of the pilonidal sinus--randomized prospective study.

UNLABELLED Multiple therapeutic approaches of the treatment of pilonidal sinuses have been described in the literature, but there are still controversies and lack of standardization. Vacuum Assisted Closure (VAC) therapy has potential beneficial effect on the wound healing after the sinus resection. THE AIM OF THE STUDY To analyze the results of VAC therapy in the treatment of pilonidal sinuses. MATERIAL AND METHODS After randomization in the control group (9 men) the simple excision of the pilonidal cyst was performed with the standard wound dressing. In the VAC group (10 men) the same surgical procedure was performed, but after the excision the VAC dressing with mobile VAC Freedom device was used. Both groups were treated in an outpatient setting under local anesthesia. The wound size, time of surgery, time of wound healing time of recovery and pain after the surgery (VAS score) were compared. RESULTS In VAC treated group the wound size and time of surgery were similar to control group. Time of wound healing, recovery and the pain after surgery in days 4-7 were reduced in comparison to the standard treated group. CONCLUSIONS VAC therapy can be easily used in an outpatient setting, mobile device is highly accepted, operation of the equipment is simple. VAC therapy significantly decreases the time of wound healing and absenteeism from work as well as the postoperative late pain.

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.

Expression of 17β-hydroxysteroid dehydrogenase type 2 is associated with some clinicopathological features in gastric cancer

In most populations, gastric cancer (GC) incidence is higher in men than in women, which may suggest the role of sex steroid hormones in gastric cancerogenesis. Both, androgens and estrogens can be synthetised in peripherial tissues. This process is controlled by expression of steroidogenic enzymes. Therefore, we evaluate the 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2) transcript and protein levels in gastric tumoral and nontumoral tissue. We also determined the association between HSD17B2 transcript and protein levels and some clinicopathological features in GC. We found significantly decreased levels of HSD17B2 transcript (P=0.00072) and protein (P=0.00017) in primary tumoral tissues of GC patients, as compared to nontumoral tissues. In patients above 60 years of age the amounts of HSD17B2 transcript (P=0.00044) and protein (P=0.00027) were significantly lower in tumoral than nontumoral tissues. Similarly, lower HSD17B2 levels, both in terms of the transcript and protein, were observed in tumoral tissues of male (P=0.013, P=0.0014), patients stomach (P=0.0062, P=0.045) and cardia (P=0.02, P=0.02) site of tumor, T3 (P=0.018, P=0.014) depth of invasion, N0 (P=0.017, P=0.045) lymph node metastasis, G3 (P=0.0027, P=0.014) malignancy grade. We also observed significantly reduced level of HSD17B2 transcript in tumoral tissue specimens of females (P=0.014), T4 depth of invasion (P=0.02), N3 lymph node metastasis (P=0.037) and G2 malignancy grade (P=0.045). Furthermore, diffuse GC histological types were associated with lower HSD17B2 protein level (P=0.024) than nontumoral tissues. We demonstrated that HSD17B2 transcript and protein levels are linked to some clinicopathological features in GC.

Endoscopic vacuum-assisted closure system (E-VAC): case report and review of the literature

Negative pressure wound therapy (NPWT) has become a standard in the treatment of chronic and difficult healing wounds. Negative pressure wound therapy is applied to the wound via a special vacuum-sealed sponge. Nowadays, the endoscopic vacuum-assisted wound closure system (E-VAC) has been proven to be an important alternative in patients with upper and lower intestinal leakage not responding to standard endoscopic and/or surgical treatment procedures. Endoscopic vacuum-assisted wound closure system provides perfect wound drainage and closure of various kinds of defect and promotes tissue granulation. Our experience has shown that E-VAC may significantly improve the morbidity and mortality rate. Moreover, E-VAC may be useful in a multidisciplinary approach – from upper gastrointestinal to rectal surgery complications. On the other hand, major limitations of the E-VAC system are the necessity of repeated endoscopic interventions and constant presence of well-trained staff. Further, large-cohort studies need to be performed to establish the applicability and effectiveness of E-VAC before routine widespread use can be recommended.

Transcript level of AKR1C3 is down-regulated in gastric cancer

Steroid hormones have been shown to play a role in gastric carcinogenesis. Large amounts of steroid hormones are locally produced in the peripheral tissues of both genders. Type 5 of 17β-hydroxysteroid dehydrogenase, encoded by the AKR1C3 gene, plays a pivotal role in both androgen and estrogen metabolism, and its expression was found to be deregulated in different cancers. In this study we measured AKR1C3 transcript and protein levels in nontumoral and primary tumoral gastric tissues, and evaluated their association with some clinicopathological features of gastric cancer (GC). We found decreased levels of AKR1C3 transcript (p < 0.0001) and protein (p = 0.0021) in GC tissues compared with the adjacent, apparently histopathologically normal, mucosa. Lower levels of AKR1C3 transcript were observed in diffuse and intestinal types of GC, whereas AKR1C3 protein levels were decreased in tumors with multisite localization, in diffuse histological type, T3, T4, and G3 grades. We also determined the effect of the histone deacetylase inhibitor sodium butyrate (NaBu) on AKR1C3 expression in EPG 85-257 and HGC-27 GC cell lines. We found that NaBu elevates the levels of both AKR1C3 transcript and protein in the cell lines we investigated. Together, our results suggest that decreased expression of AKR1C3 may be involved in development of GC and can be restored by NaBu.

Iatrogenic Bile Duct Injury. A Significant Surgical Problem. Assessment of Treatment Outcomes in the Department's Own Material

UNLABELLED Iatrogenic bile duct injuries (BDI) are still a challenging diagnostic and therapeutic problem. With the introduction of the laparoscopic technique for the treatment of cholecystolithiasis, the incidence of iatrogenic BDI increased. The aim of the study was a retrospective analysis of 69 patients treated at the department due to iatrogenic BDI in the years 2004-2014. MATERIAL AND METHODS In this paper, we presented the results of a retrospective analysis of 69 patients treated at the Department due to iatrogenic BDI in the years 2004-2014. The data were analysed in terms of age, sex, type of biliary injury, clinical symptoms, the type of repair surgery, the time between the primary surgery and the BDI management, postoperative complications and duration of hospital stay. RESULTS 82.6% of BDI occurred during laparoscopic cholecystectomy, 8.7% occurred during open cholecystectomy, whereas 6 cases of BDI resulted from surgeries conducted for other indications. In order to assess the degree of BDI, Bismuth and Neuhaus classifications were used (for open and laparoscopic cholecystectomy respectively). 84.1% of patients with confirmed BDI, were transferred to the Department from other hospitals. The average time between the primary surgery and reoperation was 6.2 days (SD 4). The most common clinical symptom was biliary fistula observed in 78.3% of patients. In 28 patients, unsuccessful attempts to manage BDI were made prior to the admission to the Department in other centres. The repair procedure was mainly conducted by laparotomy (82.6%) and by the endoscopic approach (15.9%). Hepaticojejunostomy was the most common type of reconstruction following BDI (34.7%). CONCLUSIONS The increase in the rate of iatrogenic bile duct injury remains a challenging surgical problem. The management of BDI should be multidisciplinary treatment. Referring patients with both suspected and confirmed iatrogenic BDI to tertiary centres allows more effective treatment to be implemented.

Surgical methods of treatment of intestinal passage disturbances with the characteristics of constipation in patients with intestinal stoma based on own experience.

UNLABELLED Stoma is an intestinal fistula created in emergency or by elective indications, and it is done to drain out the digestive tract content. In some patients there is a disturbance passage of gastric contents through the stoma, which may take the form of chronic constipation or even periodic subileus that will sooner or later require surgical treatment. The aim of the study was the assessment of the causes and method of treatment of constipation in patients with intestinal stoma. MATERIAL AND METHODS A total of 331 patients with stoma followed by Ostomy and Proctology Outpatient Clinic were included in the study in the years 2011-2014. The study included 146 women and 185 men and the average age was 61.3 ± 12.7 years. Within the entire froup, 273 patients had the end stoma performed whereas in 58 patients the loop stoma was created. The highest percentage of patients were the ones with diverticulosis and colorectal cancer, i.e. 132 and 114 patients respectively. A stoma was created in 35 patients due to inflammatory bowel disease (IBD), in 23 patients because of cancer, in 14 as a result of injuries and in 13 due to rectovaginal fistula. RESULTS Out of the entire group subject to study (331 patients) 93 patients (28.1%) suffered from constipation. 50 patients with constipation required surgical intervention. The most common indication for surgical treatment was the parastomal hernia (36 patients, 72%), other indications were the narrowing of the stoma (5 patients, 10%), its collapse (6 patients, 12%) or prolapse (3 patients, 6%). Parastomal hernia was responsible for 84% of constipation within the stoma and 86.1% were treated with laparotomy (31 out of 36 patients). Other causes of constipation were the stomal stenoses (5 patients), collapse of the stoma (6 patients) and stomal prolapse (3 patients). All patients were treated surgically with a good final result. CONCLUSIONS Constipation associated with dysfunction of the stoma in most cases should be treated surgically. Parastomal hernia is the most common cause of constipation in the stoma. Treatment should be performed in due time because of the possibility of developing complications, especially dangerous one is a strangulated parastomal hernia and ischemia of stoma.