Heme oxygenase-1 (HO-1) is believed to represent a key enzyme for the protection of cells against ''stress.'' Its overexpression in different types of human cancers supports the notion that HO-1 provides a growth advantage and contributes to cellular resistance against chemotherapy and radiotherapy. Given the poor survival rates of patients with pancreatic cancer due to its aggressive growth behavior and its exceptional resistance to all known forms of anticancer treatment, we have investigated the expression of HO-1 in human pancreatic cancer cells growth behavior and prognosis. Expression of HO-1 was analyzed in human pancreatic cancer samples in comparison with normal pancreas by quantitative PCR, Western blot, and confocal microscopy. The influence of radiotherapy and chemotherapy on HO-1 expression in pancreatic cancer cell lines was evaluated. Furthermore, HO-1 expression was specifically suppressed by small interfering RNA transfection and subsequently the alterations of growth behavior and resistance to anticancer treatment were tested. Human pancreatic cancer showed a 6-fold and 3.5-fold HO-1 up-regulation in comparison to normal pancreas based on mRNA and protein level, respectively (P < 0.05). Cancer tissues revealed marked HO-1 immunoreactivity in tumor cells and in tumor associated immunocytes. Treatment of the pancreatic cancer cell lines with gemcitabine or radiation strongly induced HO-1 expression. Targeted knockdown of HO-1 expression led to pronounced growth inhibition of the pancreatic cancer cells and made tumor cells significantly more sensitive to radiotherapy and chemotherapy. Therefore, specific inhibition of HO-1 expression may be a new option in pancreatic cancer therapy and may be used as sensitizer to chemotherapy and radiotherapy.

SummaryBackgroundSurgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world.MethodsThis international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231.FindingsBetween Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001).InterpretationCountries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication.FundingDFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant,...

Concepts in "fast-track" surgery, which provide optimal perioperative care, have been proven to significantly reduce complication rates and decrease hospital stay. This study explores whether fast-track concepts can also be safely applied and improve the outcomes of major pancreatic resections. Perioperative data from 255 consecutive patients, who underwent pancreatic resection by means of fast-track surgery in a high-volume medical center, were analyzed using univariate and multivariate models. Of the 255 patients, 180 received a pancreatic head resection and 51 received distal, 15 received total, and 9 received segmental pancreatectomies. The patients were discharged on median day 10 with a 30-day readmission rate of 3.5%. The in-hospital mortality was 2%, whereas medical and surgical morbidities were 17 and 25%, respectively. Fast-track parameters, such as first stools, normal food, complete mobilization, and return to normal ward, correlated significantly with early discharge (p < 0.05). Patients' age, operation time, and early extubation proved to be independent factors of early discharge, shown through multivariate analysis (odds ratio: 4.0, 2.0, and 2.8, respectively; p < 0.05). Low readmission, mortality, and morbidity rates demonstrate that fast-track surgery is in fact feasible and safe and promotes earlier discharge without compromising patient outcomes.

Background: Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis. Methods: We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients. Results: Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after “clinically successful” treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10–20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%. Conclusions: The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.

BackgroundThyroid surgeries are among the most common operations performed in the world. Hypocalcemia following total thyroidectomy is a common complication that is sometimes difficult to correct. The aim of this study is to determine the risk factors for hypocalcemia following total thyroidectomy and their clinical value.MethodsFrom January 2015 through to April 2017, 400 patients were included in this prospective multicenter study. All patients underwent total thyroidectomy due to various thyroid diseases. The following risk factors were analyzed: pre-operative and post-operative biochemical blood parameters, clinical effects and factors related to surgery, the patient, and the disease.ResultsPost-operative hypocalcemia developed in 257 patients (64.2%). Of them, 197 patients (76.7%) were diagnosed with asymptomatic hypocalcemia. Clinical symptoms were present in 60 of the 257 patients with hypocalcemia (23.3%). The statistically significant predictors of hypocalcemia were decreased calcium and ionized calcium pre-operatively (p < 0.001), parathyroid hormone on day one following surgery (p < 0.001), thyrotoxicosis <10 years before surgery (odds ratio 1.65, 95% CI 1.01–2.70, p = 0.046), the number of parathyroid glands found during surgery (odds ratio 0.52, 95% CI 0.38–0.70, p < 0.001), ligation of the trunk of the left inferior thyroid artery (odds ratio 2.04, 95% CI 1.27–3.29, p = 0.003), ligation of the trunk of the right inferior thyroid artery (odds ratio 2.37, 95% CI 1.47–3.81, p < 0.001), and the number of transplanted parathyroid glands (odds ratio 1.87, 95% CI 1.12–2.97, p = 0.015). In the multivariate analysis, age (odds ratio 1.05, 95% CI 1.01–1.09, p = 0.029) and gender (odds ratio 5.94, 95% CI 1.13–31.26, p = 0.035) were statistically significant predictors.ConclusionsThis study demonstrates that there is a number of different patient (gender, age, and duration of thyrotoxicosis <10 years before surgery) and surgical (number of parathyroid glands found during surgery, decreased calcium and ionized calcium before surgery, parathyroid hormone on day one following surgery, and ligation of the trunk of the left and right inferior thyroid artery) risk factors predictive of hypocalcemia following total thyroidectomy. Optimization of the surgical technique could possibly prevent the occurrence of hypocalcemia after total thyroidectomy in some cases; in other cases, identification of known risk factors post-operatively could permit early detection and effective treatment of these patients.

Deregulation of cellular immune system is a key event leading to severe and necrotizing AP. IL-6 and MIF could be used as early predictors of complications.

BackgroundHypomethylation of long interspersed element (LINE)-1 has been observed in tumorigenesis when using degenerate assays, which provide an average across all repeats. However, it is unknown whether individual LINE-1 loci or different CpGs within one specific LINE-1 promoter are equally affected by methylation changes. Conceivably, studying methylation changes at specific LINE-1 may be more informative than global assays for cancer diagnostics. Therefore, with the aim of mapping methylation at individual LINE-1 loci at single-CpG resolution and exploring the diagnostic potential of individual LINE-1 locus methylation, we analyzed methylation at 11 loci by pyrosequencing, next-generation bisulfite sequencing as well as global LINE-1 methylation in bladder, colon, pancreas, prostate, and stomach cancers compared to paired normal tissues and in blood samples from some of the patients compared to healthy donors.ResultsMost (72/80) tumor samples harbored significant methylation changes at at least one locus. Notably, our data revealed not only the expected hypomethylation but also hypermethylation at some loci. Specific CpGs within the LINE-1 consensus sequence appeared preferentially hypomethylated suggesting that these could act as seeds for hypomethylation. In silico analysis revealed that these CpG sites more likely faced the histones in the nucleosome. Multivariate logistic regression analysis did not reveal a significant clinical advantage of locus-specific methylation markers over global methylation markers in distinguishing tumors from normal tissues.ConclusionsMethylation changes at individual LINE-1 loci are heterogeneous, whereas specific CpGs within the consensus sequence appear to be more prone to hypomethylation. With a broader selection of loci, locus-specific LINE-1 methylation could become a tool for tumor detection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0051-y) contains supplementary material, which is available to authorized users.

IAH and ACS are rare findings in patients with mild AP. Based on the results of our study we recommend measuring the IAP in cases when patients present with SAP (APACHE II > 7; MODS > 2 or Glasgow-Imrie score > 3).