Outcomes after distal pancreatectomy with or without splenectomy for intraductal papillary mucinous neoplasm: international multicentre cohort study.

BACKGROUND: International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN. METHODS: An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy. RESULTS: Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504). CONCLUSION: This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS.

Uncinate Duct Dilatation Predicts Additional Risk for High-Grade Dysplasia or Invasive Carcinoma Among Fukuoka-Positive Intraductal Papillary Mucinous Neoplasms.

OBJECTIVE: To determine whether uncinate duct dilatation (UDD) increases the risk of high-grade dysplasia or invasive carcinoma (HGD/IC) in Fukuoka-positive intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: Though classified as a branch duct, the uncinate duct is the primary duct of the pancreatic ventral anlage. We hypothesized that UDD, like main duct dilatation, confers additional risk for HGD/IC. METHODS: A total of 467 patients met inclusion criteria in a retrospective cohort study of surgically resected IPMNs at the Massachusetts General Hospital. We used multivariable logistic regression to analyze the association between UDD (defined as ≥4 mm) and HGD/IC, controlling for Fukuoka risk criteria. In a secondary analysis, the modeling was repeated in the 194 patients with dorsal branch duct IPMNs (BD-IPMNs) in the pancreatic neck, body, or tail. RESULTS: Mean age at surgery was 70, and 229 (49%) patients were female. In total, 267 (57%) patients had only worrisome features and 200 (43%) had at least 1 high-risk feature. UDD was present in 164 (35%) patients, of whom 118 (73%) had HGD/IC. On multivariable analysis, UDD increased the odds of HGD/IC by 2.8-fold, even while controlling for Fukuoka risk factors (95% CI: 1.8-4.4, P <0.001). Prevalence of HGD/IC in all patients with UDD was 73%, compared with 74% in patients with high-risk stigmata and 73% in patients with main duct IPMNs. In the secondary analysis, UDD increased the odds of HGD/IC by 3.2-fold in patients with dorsal BD-IPMNs (95% CI: 1.3-7.7, P =0.010). CONCLUSIONS: UDD confers additional risk for HGD/IC unaccounted for by current Fukuoka criteria. Further research can extend this study to Fukuoka-negative patients, including unresected patients.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Prediction of R Status in Resections for Pancreatic Cancer Using Simplified Radiological Criteria.

OBJECTIVE: Predicting R status before surgery for pancreatic cancer (PDAC) patients with upfront surgery and neoadjuvant therapy. SUMMARY BACKGROUND DATA: Negative surgical margins (R0) are a key predictor of long-term outcomes in PDAC. METHODS: Patients undergoing pancreatic resection with curative intent for PDAC were identified. Using the CT scans from the time of diagnosis, the 2019 NCCN borderline resectability criteria were compared to novel criteria: presence of any alteration of the superior mesenteric-portal vein (SMPV) and perivascular stranding of the superior mesenteric artery (SMA). Accuracy of predicting R status was evaluated for both criteria. Patient baseline characteristics, surgical, histopathological parameters, and long-term overall survival (OS) after resection were evaluated. RESULTS: A total of 593 patients undergoing pancreatic resections for PDAC between 2010 and 2018 were identified. Three hundred and twenty-five (54.8%) patients underwent upfront surgery, whereas 268 (45.2%) received neoadjuvant therapy. In upfront resected patients, positive SMA stranding was associated with 56% margin positive resection rates, whereas positive SMA stranding and SMPV alterations together showed a margin positive resection rate of 75%. In contrast to these criteria, the 2019 NCCN borderline criteria failed to predict margin status. In patients undergoing neoadjuvant therapy, only perivascular SMA stranding remained a predictor of margin positive resection, leading to a rate of 33% R+ resections. Perivascular SMA stranding was related to higher clinical T stage (P = 0.003) and clinical N stage (P = 0.043) as well as perineural invasion (P = 0.022). SMA stranding was associated with worse survival in both patients undergoing upfront surgery (36 vs 22 months, P = 0.002) and neoadjuvant therapy (47 vs 34 months, P = 0.050). CONCLUSIONS: The novel criteria were accurate predictors of R status in PDAC patients undergoing upfront resection. After neoadjuvant treatment, likelihood of positive resection margins is approximately halved, and only perivascular SMA stranding remained a predictive factor.

ABO blood group distribution and risk of malignancy in patients undergoing resection for intraductal papillary mucinous neoplasm (IPMN).

BACKGROUND: The ABO blood type has been associated with risk of development of several malignancies, including pancreatic cancer. Data regarding IPMN is equivocal. To investigate this further, we analyzed the association between the ABO blood group and the presence of malignancy in a large cohort of resected IPMN and its influence in survival. METHODS: 819 patients who underwent pancreatic resection for IPMN in the Massachusetts General Hospital (MGH) and Cambridge University Hospitals NHS Foundation Trust (CUH) from January 1993 to December 2020 were identified from prospective institutional databases. Pathological characteristics and blood type were correlated. RESULTS: The distribution of blood types A, B, AB and O was 384 (47%), 92 (11%), 44 (5%) and 299 (37%), respectively. This blood type distribution was different than the reference population of the MGH and the CUH, which is 55% non-O blood group, and 45% type O. There was a significant predominance of non-O blood types when compared with O-blood type in patients with malignant IPMN (i.e. patients with high-grade dysplasia and invasive cancer) (67% vs 33%, OR 1.31 95%CI: 0.98-1.75, p = 0.069). The association was stronger for IPMN with invasive cancer (OR 1.43 95%CI: 1.01-2.02, p = 0.039). Blood group did not influence survival. CONCLUSION: Non-O blood type is associated with need for resection in IPMN and with presence of invasive carcinoma.

Patient-Related Factors Associated With Stoma and Peristomal Complications Following Fecal Ostomy Surgery: A Scoping Review.

PURPOSE: Ostomy creation is often an integral part of the surgical management of various diseases including colorectal malignancies and inflammatory bowel disease. Stoma and peristomal complications may occur in up to 70% of patients following ostomy surgery. The aim of this scoping literature review was to synthesize evidence on the risk factors for developing complications following creation of a fecal ostomy. DESIGN: Scoping literature review. SEARCH STRATEGY: Two independent researchers completed a search of the online bibliographic databases PubMed, MEDLINE, Cochrane, Google Scholar, and EMBASE for all articles published between January 1980 and December 2018. The search comprised multiple elements including systematic literature reviews with meta-analysis of pooled findings, randomized controlled trials, cohort studies, observational studies, other types of review articles, and multiple case reports. We screened 307 unique titles and abstracts; 68 articles met our eligibility criteria for inclusion. The methodological rigor of study quality included in our scoping review was variable. FINDINGS/CONCLUSIONS: We identified 6 risk factors associated with an increased likelihood of stoma or peristomal complications (1) age more than 65 years; (2) female sex; (3) body mass index more than 25; (4) diabetes mellitus as a comorbid condition; (5) abdominal malignancy as the underlying reason for ostomy surgery; and (6) lack of preoperative stoma site marking and WOC/ostomy nurse specialist care prior to stoma surgery. We also found evidence that persons with a colostomy are at a higher risk for prolapse and parastomal hernia. IMPLICATIONS: Health care professionals should consider these risk factors when caring for patients undergoing fecal ostomy surgery and manage modifiable factors whenever possible. For example, preoperative stoma site marking by an ostomy nurse or surgeon familiar with this task, along with careful perioperative ostomy care and education of the patient by an ostomy nurse specialist, are essential to reduce the risk of modifiable risk factors related to creation of a fecal ostomy.

Radiation-induced rectovaginal fistulas in locally advanced gynaecological malignancies-new patients, old problem?

PURPOSE: Radiation-induced rectovaginal fistula (RI-RVF) is a chronic and serious condition with a significant influence on quality of life. The aim of this study is to evaluate the results of surgical treatment of rectovaginal fistulas of patients previously undergoing radiotherapy. METHODS: Fifty patients treated in the Gynaecological Radiotherapy Unit for gynaecologic malignancy and in the Department of General and Colorectal Surgery for RI-RVF between 2003 and 2013 were enrolled into a prospectively maintained database and underwent regular follow-up examinations in an outpatient clinic, during which surgical outcomes were assessed. RESULTS: Median age was 60 years (range 40-84 years). Cervical cancer was the most common cause of radiotherapy. Median time of fistula development after radiotherapy was 20 months (range 5-240 months). In 48 (96%) patients, only faecal diversion could be performed, while two patients underwent rectal resection. The fistula healed in six patients. Factors that correlated with fistula healing were a distance from the anal verge above 7 cm (p = 0.007 OR 18 95%CI 2.2609-14.3062) and creation of loop ileostomy (p = 0.08 OR 17 95%CI 1.2818-23.9701), whereas a prolonged course of radiotherapy of more than 6 weeks (p = 0.047) correlated negatively. In multivariate analysis, only distance from the anal verge remained significant (p = 0.031 OR 2.35 95%CI 1.0422-5.2924). CONCLUSIONS: The treatment of radiation-induced rectovaginal fistulas needs to be tailored individually to each patient. Faecal diversion remains the simplest and safest method of treating RI-RVF, especially in the group of patients who cannot undergo complicated surgical procedures, and offers acceptable quality of life.

Negative predictive value of drain amylase concentration for development of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.

Extracellular vesicle analysis of plasma allows differential diagnosis of atypical pancreatic serous cystadenoma.

Increased use of cross-sectional imaging has resulted in frequent detection of incidental cystic pancreatic lesions. Serous cystadenomas (SCAs) are benign cysts that do not require surgical intervention unless symptomatic. Unfortunately, up to half of SCAs do not have typical imaging findings ("atypical SCAs"), overlap with potentially malignant precursor lesions, and thus pose a diagnostic challenge. We tested whether the analysis of circulating extracellular vesicle (EV) biomarkers using a digital EV screening technology (DEST) could enhance the discrimination of cystic pancreatic lesions and avoid unnecessary surgical intervention in these atypical SCAs. Analysis of 25 different protein biomarkers in plasma EV from 68 patients identified a putative biomarker signature of Das-1, Vimentin, Chromogranin A, and CAIX with high discriminatory power (AUC of 0.99). Analysis of plasma EV for multiplexed markers may thus be helpful in clinical decision-making.

Identification of high-risk features in mucinous cystic neoplasms of the pancreas.

BACKGROUND: Mucinous cystic neoplasms of the pancreas are uncommon tumors that have the potential of becoming cancer. There is no consensus regarding the high-risk features of these tumors. Our study aimed to identify the preoperative demographic, clinical, or radiologic factors that can predict the presence of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. METHODS: We identified 157 patients who underwent resection and fulfilled the pathologic criteria for mucinous cystic neoplasms of the pancreas in a prospectively maintained database spanning 3 decades (1990-2020). Multivariable logistic regression was used to identify predictors of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas. RESULTS: The rate of high-grade dysplasia or invasive carcinoma was 11%. Tumor size ≥4 cm (P < .001), mural nodularity (P = .04), and a serum CA 19-9 level >37 U/mL (P < .001) were associated with high-grade dysplasia or invasive carcinoma. In the multivariable analysis, tumor size ≥4 cm (odds ratio 16.9, 95% confidence interval 2.04-140, P = .009) and a CA 19-9 level >37 U/mL (odds ratio 5.68, 95% confidence interval 1.52-21.3, P = .010) were predictors of high-grade dysplasia or invasive carcinoma. There were no tumors with high-grade dysplasia or invasive carcinoma in patients with tumor size <4 cm in the absence of an elevated CA 19-9 or mural nodularity. CONCLUSION: Tumors with a size ≥4 cm and/or a high CA 19-9 level should be considered for prompt surgical resection. Conversely, tumors <4 cm with no other high-risk features have a negligible risk for high-grade dysplasia or invasive carcinoma and may benefit from nonoperative surveillance. Mural nodularity is an additional suspicious feature. These findings may contribute to future guidelines.

Bioactive Lavandula angustifolia essential oil-loaded nanoemulsion dressing for burn wound healing. In vitro and in vivo studies.

The aim of this study was to develop a dressing with bioactive lavender in a new form of nanoemulsion, and to verify its biosafety and effectiveness in burn wound healing. As part of this research, the composition of the bioactive carrier of lavender oil in the form of a nanoemulsion obtained using ultrasound was optimised. The mean particle size of the internal phase and polydispersity were determined using the dynamic light scattering method using a Zestasizer NanoZS by Malvern and using cryo-transmission electron microscopy (TEM). These studies confirmed that the selected formulation had a particle size of approximately 180 nm and remained stable over time. The preparation was also subjected to rheological analysis (viscosity approximately 480 mPa·s) and a pH test (approximately 6). A macroemulsion (ME) with the same qualitative composition was developed as a reference. Nanoformulations and MEs were tested for skin penetration using Raman spectroscopy in an in vitro model. Research has shown that both formulations deliver oil to living layers of the skin. Subsequently, studies were conducted to confirm the effect of lavender oil in emulsion systems on the mitigation of the inflammatory reaction and its pro-regenerative effect on the wound healing process in an in vitro cell culture model. The safe concentration of the oil in the emulsion preparation was also determined based on preliminary in vivo tests of skin sensitisation and irritation as well as an hemocompatibility test of the preparation.

Single-EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer.

Tumor cell-derived extracellular vesicles (EVs) are being explored as circulating biomarkers, but it is unclear whether bulk measurements will allow early cancer detection. We hypothesized that a single-EV analysis (sEVA) technique could potentially improve diagnostic accuracy. Using pancreatic cancer (PDAC), we analyzed the composition of putative cancer markers in 11 model lines. In parental PDAC cells positive for KRASmut and/or P53mut proteins, only ~40% of EVs were also positive. In a blinded study involving 16 patients with surgically proven stage 1 PDAC, KRASmut and P53mut protein was detectable at much lower levels, generally in <0.1% of vesicles. These vesicles were detectable by the new sEVA approach in 15 of the 16 patients. Using a modeling approach, we estimate that the current PDAC detection limit is at ~0.1-cm3 tumor volume, below clinical imaging capabilities. These findings establish the potential for sEVA for early cancer detection.

Number of Worrisome Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasm.

BACKGROUND: The 2017 revised International Association of Pancreatology guidelines for management of intraductal papillary mucinous neoplasm (IPMN) describe worrisome features (WF) and high-risk stigmata (HRS), recommending resection in the latter and further work-up and close surveillance for patients with WF. The effect of multiple WF on the likelihood of malignancy has not been evaluated. STUDY DESIGN: Eight hundred ten patients who underwent pancreatic resection for IPMN in 2 tertiary referral centers were identified from prospective institutional databases. Patients were retrospectively categorized into subgroups according to the number of WF or HRS and presence of malignancy, defined as high-grade dysplasia (HGD) or invasive cancer on final pathology. RESULTS: Three hundred seventy-nine (47%) patients had HRS, 370 (46%) had 1 or more WF, and 61 patients (7%) had neither. Malignancy was present in 70% (n = 267) of patients with HRS and in 30% (n = 127) of those with WF. Only 3 of 61 patients without WF/HRS had malignancy, and all only in the form of HGD. The risk of malignancy increased in a stepwise fashion with the number of WF, to 22%, 34%, and 59% with 1, 2, and 3 WF, respectively (p = 0.001), and reached 100% in patients with 4 or more WF. Although the relative risks differed for particular WF, the areas under the curve were not statistically different. CONCLUSION: We confirm that presence of HRS in IPMN is associated with a very high likelihood of malignancy. The presence of a single WF has a malignancy risk of 22%, and additional WF increase this risk significantly. When 3 or more WF are present, the risk is similar to that of HRS.

Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.

Patient-reported outcomes after minimally invasive retroperitoneal pancreatic necrosectomy to treat acute pancreatitis: An exploratory study.

OBJECTIVE: The aim of this study (abbreviated as QUANTUM) was to assess the quality of life (QoL) of patients who underwent minimally invasive retroperitoneal pancreatic necrosectomy (MIRPN) for acute pancreatic necrosis with or without infection of necrotic tissue collections after discharge and to compare the patient-reported outcomes (PRO) in these patients with published data in normative population. METHODS: Patients with acute pancreatitis who underwent MIRPN between January 2010 and December 2016 were identified and invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC PAN28(CP) questionnaires. PRO were compared using Pearson correlation coefficient and ANOVA (significance P < 0.01) with an age- and sex-matched normative population of western Europe, stratified by age, and also the time duration after MIRPN (<3 y and >3 y). A change >15 points in the PRO score was taken as clinically important. RESULTS: Among 52 eligible patients identified, 46 (88%) agreed to participate, 74% returned questionnaires. After the MIRPN all patients had worse physical and social functioning scores with a clinically important (>15 points) reduction in those ≤50 years; while fatigue, pain and insomnia symptom scales had the highest scores (42, 26 and 30 points, respectively). Patients <3 years after MIRPN had similar scores for all functional scales and global health-related quality of life (HRQoL) compared to the normative population. However, over time their global HRQoL deteriorated and after 3 years their scores for functioning and symptoms were statistically (P < 0.0001) and clinically (>15 points) worse than those in age-matched controls. CONCLUSIONS: During the first 3 years after the MIRPN patients have a relatively high QoL but report worse fatigue than the normative population. However, patients should be informed that their HRQoL deteriorates with time, often due to chronic pancreatitis and pancreatic insufficiency. This study supports the use of MIRPN and prospective studies of HRQoL in this setting are indicated.

An Analysis of IL-10, IL-17A, IL-17RA, IL-23A and IL-23R Expression and Their Correlation with Clinical Course in Patients with Psoriasis.

Being one of the most common dermatological inflammatory disorders, psoriasis is a frequent subject of research. It is considered to be a T cell-dependent immune disease whose pathogenesis is influenced by cytokines, such as IL-10, IL-17A, IL-17RA, IL-23A and IL-23R. The present study examines whether the expression of selected genes is correlated with the clinical course of psoriasis, assessed by the PASI, BSA and DLQI scales. Skin biopsies and blood from 60 patients with psoriasis and 24 healthy controls were obtained for RNA isolation. These were subjected to RT-PCR for IL-10, IL-17A, IL-17RA, IL-23A and IL-23R genes. The results were presented as an RQ value. IL-17A and IL-23R expression levels were higher in psoriatic skin compared to controls, while IL-10 expression was lower. A positive correlation was also found between RQ for IL-23A and PASI index. Psoriatic skin is characterised by elevated expression of IL-17A and IL-23R and decreased expression of IL-10. This indicates that the selected cytokines may be one of the factors involved in the pathogenesis and pathomechanism of psoriasis, but more studies need to be made before we can elucidate the exact reason for the unbalance in cytokine expression levels.

Analysis of molecular markers as IL-12, IL-22 and IFN-γ in correlation with a clinical course in patients with psoriasis.

OBJECTIVES: As a chronic, recurrent, immunologically mediated systemic disease and a common cause of dermatological problems, psoriasis is often a subject of scientific research. Skin changes located on the hands can cause difficulties and limitations in the performance of professional activities, especially manual ones. The main role in pathogenesis is played by immunological factors - improper functioning of the components of the immune system, among others, T lymphocytes and cytokines like interleukin-12 (IL-12), interleukin-22 (IL-22) and interferon gamma (IFN-γ). MATERIAL AND METHODS: The obtained tissue and blood were destined for RNA isolation. The RNA was then subjected to a reverse transcription reaction. The relative gene expression level was evaluated by the real-time polymerase chain reaction for IL-12B, IL-22 and IFN-γ genes, and presented as the relative quantification (RQ) value, relative to the reference gene GAPDH. In addition, a correlation analysis of the expression level of selected genes with the clinical course of the disease, as assessed by the Psoriasis Area and Severity Index (PASI), the Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI) scores was performed. RESULTS: Statistical analysis confirmed a significant increase in RQ values for IL-12B, IL-22 and IFN-γ in the group of psoriatic patients vs. the control group. A positive correlation was also found between BSA and PASI and RQ for the IL-12B gene. CONCLUSIONS: Increased expression levels of IL-12B, IL-22 and IFN-γ genes in psoriatic skin confirm that selected cytokines play an important role in the initiation and sustenance of psoriasis. Int J Occup Med Environ Health. 2020;33(5):635-47.

Sexual activity in patients after proctocolectomy with ileal pouch-anal anastomosis.

<b>Introduction:</b> Proctocolectomy with ileal pouch-anal anastomosis is the gold standard in the surgical treatment of patients with ulcerative colitis, familial adenomatous polyposis and other colorectal diseases requiring colectomy. The treatment consists in removing the large intestine and creating an intestinal reservoir from the last ileum loop and then anastomosing the intestinal reservoir with the anal canal. Like any surgical procedure, RPC-IPAA also carries the risk of complications, both early and late. Late postoperative complications include sexual dysfunction. <br><b>Aim:</b> The main goal of the following work is to assess the quality of life and sexual activity in patients having undergone the RPC-IPAA procedure at the General and Colorectal Surgery Clinic. <br><b>Material and methods:</b> The study group consisted of patients aged 19-79 who had been subjected to RPC-IPAA procedures at the General and Colorectal Surgery Clinic in years 2010-2019. The study was conducted on the basis of a survey consisting of 50 questions about the social and mental condition, medical history and previous treatment as well as the quality of sexual life before and after surgery. The scale used for the assessment of the quality of sex life consisted of 5 grades: very low, low, medium, high, very high. Thirty subjects (21 men and 9 women) took part in the survey. Ulcerative colitis (86.6%) was the most common reason for qualification for restorative proctectomy among the examined patients; less common reasons included familial adenomatous polyposis (13.3%) and synchronous colorectal cancer (3.3%). A vast majority of the surgeries had been performed after 10 years' duration of ulcerative colitis, and the intestinal reservoir had been functioning for over a year at the time of the examination. In addition, the effect of taking steroids and the impact of early postoperative complications on the quality of sex life of patients was assessed. <br><b>Results:</b> High or very high sexual activity before surgery was reported by 46% of patients whereas low or very low quality was reported by 13%. The rest of the responders assessed their pre-operative sexual activity as average. After surgery, 23% of patients rated their sexual activity as high or very high while 36.6% of patients rated it as low or very low (P = 0.07). It was also noted that taking corticosteroids before surgery decreased the quality of sex life after surgery (P = 0.07 for activity, P = 0.04 for quality). None of the women surveyed used artificial moisturizing of intimate places during sex. Only 1 person stated that they started using artificial moisturization of intimate places after the procedure (P = 0.5). None of the men surveyed had used pharmacological agents to help them obtain an erection before surgery while as many as 33% of responders reported the need for their use after surgery (P = 0.008). Other postoperative sexual dysfunctions were also registered, such as dyspareunia (13.3%), sensory disorder within the intimate region, fecal incontinence, and urinary incontinence. <br><b>Conclusions:</b> To sum up, sexual activity and quality of sexual life deteriorated after RPC-IPAA in our patients.

Association of XRCC6 C1310G and LIG4 T9I polymorphisms of NHEJ DNA repair pathway with risk of colorectal cancer in the Polish population.

INTRODUCTION: Colorectal cancer is the second most common cancer worldwide. DNA double strand breaks (DSBs) are the most dangerous lesions which can lead to carcinogenesis. Nonhomologous end joining (NHEJ) is an important pathway, that allows for recovering DNA by direct end joining. The XRCC6 and LIG4 genes encode respectively Ku70 protein and human ATP-dependent DNA ligase, which are the components of the NHEJ repair pathway. The aim of our study was to evaluate the influence of XRCC6 C1310G and LIG4 T9I genes polymorphisms on colorectal cancer risk among Polish population. MATERIALS AND METHOD: Genotyping was performed using TaqMan probes based on analysis of PCR products amplified in Real Time PCR. The research has been carried out on the material obtained from 100 patients with colorectal cancer and 100 cancer-free individuals who were age and sex-matched as a control group. The results were developed using the chi - squer test and odds ratio (OR). RESULTS: Odd ratio analysis indicates reduced risk of colorectal cancer for LIG4 T9I polymorphism in heterozygotus model C/T (OR= 0.2717 95% CI= 0.1247-0,5918) and homozygous model T/T (OR= 0.3593 95% CI= 0.1394-0.9266). Similar situation we observed for XRCC6 C1310G gene polymorphism, which indicated on heterozygotus variant C/G (OR= 0.1181 95% CI= 0.0145-0.964) and homozygotus variant G/G (OR= 0.0972 95% CI= 0.0097-0.9713) to decrease the risk of colorectal cancer. Conslusions: Our research revealed XRCC6 C1310G and LIG4 T9I polymorphisms are associated with diminished risk of colorectal cancer. However, to confirm obtained results, a further investigations should be carried out.

An in vivo biocompatibility study of surgical meshes made from bacterial cellulose modified with chitosan.

Bacterial cellulose modified with chitosan (MBC) is an innovative biomaterial used in regenerative medicine which may potentially improve treatment outcomes mesh for hernia repair surgery by facilitating better absorption in native tissue with less risk of mesh-related infections. The aim of the present study was to evaluate the biocompatibility of mesh based on MBC, and determine whether immunological reactions occur due to hypersensitivity to the implants. Forty five Imp:WIST rats were randomly assigned to be implanted with one of three mesh types: simple polypropylene mesh (n = 15), mesh modified by bacterial cellulose only (n = 15) and MBC mesh (n = 15) and evaluated after one and three months following intramuscular implantation. For MBC mesh, basic toxicological studies, i.e. Acute Dermal Irritation, Intradermal Reactivity and Acute Sensitization (GPMT), were also carried out on 9 Imp:BN albino rabbits and 15 Imp:D-H guinea pigs. The lowest immune response and the highest degree of fibroplasia were observed for MBC mesh both after one and three months after implantation. Toxicological studies classified the tested MBC mesh as a barely perceptible irritant with no signs of sensitization or allergic reactions observed during the studies. The findings indicate that MBC mesh does not irritate, does not sensitize and does not cause hypersensitivity in the implant site, and therefore presents a low risk of provoking such reactions in humans.