Next-generation microbiological testing in intraabdominal infections with PCR technology.

PURPOSE: Intraabdominal infections (IAI) are increasing worldwide and are a major contributor to morbidity and mortality. Among IAI, the number of multi-drug resistant organisms (MDRO) is increasing globally. We tested the Unyvero A50® for intraabdominal infections, compared the detected microorganisms and antibiotic resistance, and compared the results with those of routine microbiology. METHODS: We prospectively compared samples obtained from surgical patients using PCR-based Unyvero IAI cartridges against routine microbiology for the detection of microorganisms. Additionally, we identified clinical parameters that correlated with the microbiological findings. Data were analyzed using the t-test and Mann-Whitney U test. RESULTS: Sixty-two samples were analyzed. The PCR system identified more microorganisms, mostly Bacteroides species, Escherichia coli, and Enterococcus spp. For bacterial resistance, the PCR system results were fully concordant with those of routine microbiology, resulting in a sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of 100%. The sensitivity, specificity, PPV, and NPV for the detection of microorganisms were 74%, 58%, 60%, and 72%, respectively. CRP levels were significantly higher in patients with detectable microorganisms. We identified more microorganisms and bacterial resistance in hospital-acquired intra-abdominal infections by using the PCR system. DISCUSSION: IAI warrants early identification of the microorganisms involved and their resistance to allow for adequate antibiotic therapy. PCR systems enable physicians to rapidly adjust their antibiotic treatment. Conventional microbiological culture and testing remain essential for determining the minimal growth inhibition concentrations for antibiotic therapy.

Unusual paraneoplastic syndromes in pancreatic cancer: a case report of Lambert-Eaton myasthenic syndrome (LEMS) associated with intraductal papillary mucinous cancer of the pancreas.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction. It can occur as a paraneoplastic disorder associated with various types of carcinomas, usually small cell lung cancer or as an autoimmune disease. LEMS can be misdiagnosed as myasthenia gravis or as an oncological sequela, causing delays in diagnosis. We present a rare case of a male adult with confirmed LEMS occurring with pancreatic carcinoma. Case Description: A 66-year-old man presented with a newly diagnosed pancreatic tumor. He had been experiencing weakness and fatigue in his lower extremities since the summer of 2020. Over time, the weakness progressed to include his proximal upper extremity muscles. Dysphonia, dysarthria, decreased appetite and significant weight loss were also observed. A computed tomography (CT) scan revealed a 3 cm locally resectable cystic tumor in the pancreatic head. Blood tests showed elevated carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels. A Whipple procedure was performed, which revealed a poorly differentiated pancreatic adenocarcinoma inside an intraductal pancreatic mucinous neoplasm. Postoperatively, the patient was admitted to the intensive care unit (ICU) because he had no spontaneous breathing and manifested areflexia signs. A train of four (TOF) monitoring of peripheral nerve stimulation was performed and pyridostigmine therapy was initiated, leading to an improvement in symptoms allowing the extubation and transfer to the peripheral ward. Further diagnostic tests revealed a LEMS and an intravenous therapy with cumulative 100 g immunoglobulin (Ig) G was initiated. Upon discharge, 10 days after starting LEMS treatment, the patient showed subjective and objective improvement in strength. Conclusions: Paraneoplastic syndromes are more common than expected, but rare in pancreatic adenocarcinoma. They can appear before abdominal symptoms, facilitating early diagnosis. Successful treatment of cancer may eliminate paraneoplastic symptoms. LEMS may reveal pancreatic cancer. Early recognition of paraneoplastic syndromes is important for pancreatic cancer management. Further investigation is needed to evaluate the diagnostic approach for LEMS in all patients with pancreatic cancer.

GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells.

GP-2250, a novel anticancer agent, severely limits the energy metabolism, as demonstrated by the inhibition of hexokinase 2 and glyceraldehyde-3-phosphate dehydrogenase and a decrease of ATP. Rescue experiments with supplementary pyruvate or oxaloacetate demonstrated that a TCA cycle deficit largely contributed to cytotoxicity. Activation of the energy-deficit sensor, AMP-dependent protein kinase, was associated with increased phosphorylation of acetyl-CoA carboxylase and Raptor, pointing to a possible deficit in the synthesis of fatty acids and proteins as essential cell components. Binding of p65 to DNA was dose-dependently reduced in nuclear lysates. A transcriptional deficit of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) was substantiated by the downregulation of cyclin D1 and of the anti-apoptotic Bcl2, in line with reduction in tumour cell proliferation and induction of apoptosis, respectively. The upregulation of p53 concomitant with an excess of ROS supported apoptosis. Thus, the anticancer activity of GP-2250 is a result of disruption of energy metabolism and inhibition of tumour promotion by NF-κB.

Applicability of the surgical risk calculator by the American College of Surgeons in the setting of German patients undergoing complete pancreatectomy: multicentre study using data from the StuDoQ|Pancreas registry.

INTRODUCTION: Surgical risk calculators can estimate risk probabilities for postoperative outcomes utilizing patient-specific risk factors. They provide meaningful information for obtaining informed consent. The aim of the present paper was to evaluate the predictive value of the surgical risk calculators by the American College of Surgeons in German patients undergoing total pancreatectomy. METHODS: Data for patients who underwent total pancreatectomy between 2014 and 2018 were acquired from the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery. Risk factors were entered manually into the surgical risk calculators and calculated risks were compared with actual outcomes. RESULTS: Of the 408 patients analysed, predicted risk was higher in patients with complications except for the prediction of re-admission (P = 0.127), delayed gastric emptying (P = 0.243), and thrombosis (P = 0.256). In contrast, classification of patients into below, above, or average risk by the surgical risk calculators only produced meaningful results for discharge to nursing facility (P < 0.001), renal failure (P = 0.003), pneumonia (P = 0.001), serious complications, and overall morbidity (both P < 0.001). Assessment of discrimination and calibration showed poor results (scaled Brier scores 8.46 per cent or less). CONCLUSION: Overall surgical risk calculator performance was poor. This finding promotes the development of a specific surgical risk calculator applicable to the German healthcare system.

Risk Factor Identification for Delayed Gastric Emptying after Distal Pancreatectomy-An Evaluation of 1688 Patients Based on the German StuDoQ|Pancreas Registry.

Delayed gastric emptying (DGE) ranks as one of the most frequent complications in pancreatic surgery. It leads to increased costs for healthcare systems, lengthened hospital stays and reduced quality of life. Data about DGE after distal pancreatectomy (DP) are scarce. The StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery provided data of patients who underwent distal pancreatectomy from 1 January 2014 to 31 December 2018. The retrospective evaluation included comprehensive data: 1688 patients were enrolled; DGE occurred 160 times (9.5%); grade "A" was reported for 98 (61.3%), grade "B" for 41 (25.6%) and grade "C" for 21 (13.1%) patients. In univariate analysis pancreatic fistulas were associated with higher frequencies of intraabdominal abscesses (9.1% vs. 2%, p > 0.001), postpancreatectomy haemorrhage (8.1% vs. 3.7%, >0.001) and DGE (14.5% vs. 6%, p < 0.001). According to multivariate analysis, "abscesses with invasive therapy" (p < 0.001), "other surgical complications" (p < 0.001), prolonged "stays in ICU" (p < 0.001), lengthened duration of surgery (p < 0.001) and conventional surgery (p = 0.007) were identified as independent risk factors for DGE. Perioperative and postoperative factors were identified as risk factors for DGE. Following research should examine this highly relevant topic in a prospective, register-based manner. As there is no causal therapy for DGE, its avoidance is of major importance.

Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma-A 3-D In Vitro Study.

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.

New Therapy Options for Neuroendocrine Carcinoma of the Pancreas-The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo.

Neuroendocrine carcinoma of the pancreas (pNEC) is an aggressive form of neuroendocrine tumor characterized by a rising incidence without an increase in survival rates. GP-2250 is an oxathiazinane derivate possessing antineoplastic effects, especially in combination with Gemcitabine on the pancreatic adenocarcinoma. The cytotoxic effects of the monotherapy of GP-2250 (GP-2250mono) and Gemcitabine (Gemmono), as well as the combination therapy of both, were studied in vitro using an MTT-assay on the QGP-1 and BON-1 cell lines, along with in vivo studies on a murine xenograft model of QGP-1 and a patient-derived xenograft model (PDX) of Bo99. In vitro, Gemmono and GP-2250mono showed a dose-dependent cytotoxicity. The combination of GP-2250 and Gemcitabine exhibited highly synergistic effects. In vivo, the combination therapy obtained a partial response in QGP-1, while GP-2250mono and Gemmono showed progressive disease or stable disease, respectively. In Bo99 PDX, the combination therapy led to a partial response, while the monotherapy resulted in progressive disease. No development of secondary resistances was observed, as opposed to monotherapy. This study was the first to evaluate the effects of the emerging substance GP-2250 on pNEC. The substance showed synergism in combination with Gemcitabine. The combination therapy proved to be effective in vitro and in vivo, without the development of secondary resistances.

Quantum Relativity of Subsystems.

One of the most basic notions in physics is the partitioning of a system into subsystems and the study of correlations among its parts. In this Letter, we explore this notion in the context of quantum reference frame (QRF) covariance, in which this partitioning is subject to a symmetry constraint. We demonstrate that different reference frame perspectives induce different sets of subsystem observable algebras, which leads to a gauge-invariant, frame-dependent notion of subsystems and entanglement. We further demonstrate that subalgebras which commute before imposing the symmetry constraint can translate into noncommuting algebras in a given QRF perspective after symmetry imposition. Such a QRF perspective does not inherit the distinction between subsystems in terms of the corresponding tensor factorizability of the kinematical Hilbert space and observable algebra. Since the condition for this to occur is contingent on the choice of QRF, the notion of subsystem locality is frame dependent.

Impact of pylorus preservation on delayed gastric emptying after pancreaticoduodenectomy-analysis of 5,000 patients based on the German StuDoQ|Pancreas-Registry.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic head resection. It leads to increased length of hospital stay, high costs for healthcare systems and reduced quality of life. The primary aim of the study was to assess the impact of pylorus preservation, respectively resection on the occurrence of DGE in patients undergoing pancreaticoduodenectomy (PD). METHODS: All cases of pylorus-resecting PD (PRPD) and pylorus-preserving PD (PPPD) entered in the StuDoQ|Pancreas nationwide registry of the German Society of General and Visceral Surgery from 01/01/2014 until 31/12/2018 including demographics, surgical techniques, histopathological and perioperative data were retrospectively analyzed. This study was approved by the ethics committee of the Ruhr-University Bochum, Germany. RESULTS: Data of 5,080 patients were enrolled. PPPD was the method of choice (70.4%). Pylorus preservation had no impact on the occurrence of DGE (20.3% vs. 21.5%, P=0.33), but further risk factors could be identified. The comparison of PPPD and PRPD groups showed statistically significant differences in the surgical approach (primary open approach, 94.8% vs. 98.0%, P<0.001), duration of surgery (326.4 vs. 352.1 minutes, P<0.001), technique of pancreatic anastomosis (pancreaticojejunostomy vs. pancreaticojejunostomy), 78.6% vs. 85.2%, P<0.001). CONCLUSIONS: Patient factors, intraoperative factors, duration of surgery and postoperative factors (postoperative pancreatic fistula, biliary leakage and other surgical complications) were identified as risk factors for DGE. Future research should focus on register-based, prospective, randomised-controlled studies such as the currently recruiting "PyloResPres trial".

Late recurrences of pancreatic cancer in patients with long-term survival after pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer remains a relevant clinical problem due to poor prognosis. Even after curative pancreaticoduodenectomy tumor recurrences occur in up to 80%. Risk factors for postoperative tumor recurrences have been identified before, but data on risk factors for tumor recurrences in patients with long-term-survival is scarce. METHODS: In this retrospective study consecutive long-term survival-patients (defined as at least 60 months survival) undergoing pancreaticoduodenectomy for pancreatic cancer from 2007-2014 were identified in the 2nd largest pancreatic surgery center in Germany. Clinical, pathohistological and laboratory values were analyzed to identify risk factors for tumor recurrence. RESULTS: Thirty-four of one-hundred-sixty-seven patients were identified as long-term-survival-patients in the study period. Of those, 10 patients (29.4%) suffered from tumor recurrence. Lymph vessel invasion was identified as an independent risk factor (P=0.031, hazard ratio 13.127, 95% confidence interval: 1.270-135.698). Median postoperative time to tumor recurrence in long-term-survival-patients was 49 months. Overall survival after diagnosis of tumor recurrence was 33 months. 80% (N=8) of the patients were asymptomatic. Half of the patients (N=5) suffered from local disease, with 40% undergoing curative tumor resection. CA 19-9 levels were significantly elevated at 57 U/mL (normal <27 U/mL). CONCLUSIONS: Tumor recurrence in long-term-survival-patients is typically asymptomatic. Especially long-term-survival-patients with lymph vessel invasion are more likely to develop tumor recurrence. Therefore, a structured follow-up program including CT-scans and CA 19-9 surveillance must be continued in all patients undergoing pancreaticoduodenectomy even in cases of long-term-survival.

Recurrence of Pancreatic Ductal Adenocarcinoma after Complete Histopathological Remission Caused by FOLFIRINOX.

We previously reported 2 cases of pathologic complete response (pCR) of a pancreatic cancer (PC) following neoadjuvant FOLFIRINOX treatment. We now complete our report by a follow-up on both patients. Patient 1 achieved a disease-free survival of 12 months after initial resection until she developed a singular hepatic metastasis. Treatment by FOLFIRINOX and complete removal of the metastasis by atypical liver resection after 6 months allowed for another 12 months of disease control. After intra-abdominal tumor recurrence and development of intracerebral metastases, the patient died 34 months after primary diagnosis. Patient 2 developed hepatic tumor recurrence only 3 months after initial resection. However, treatment by FOLFIRINOX led to a stable disease for 27 months after resection and was followed by atypical liver resection of multiple segments. Six months later, another hepatic recurrence was suspected. Via next-generation sequencing (NGS) of the tumor genome, a deleterious mutation in the ataxia telangiectasia-mutated (ATM) gene, causing a BRCAness, was detected. After initial treatment by FOLFOX, maintenance therapy with the poly-ADP-ribose-polymerase (PARP) inhibitor olaparib was initiated. The patient is now alive for 54 months after initial diagnosis of metastasized pancreatic adenocarcinoma. Tumor recurrence is possible even after pCR of PC and remains challenging. In case of multifocal tumor recurrence, chemotherapy remains the standard treatment. Recently, genetic sequencing allows individualized treatments. In selected cases, highly specialized teams can offer a variety of therapeutic options leading to previously unseen clinical courses.

Is surgery for serous cystic neoplasms of the pancreas still indicated? Sixteen years of experience at a high-volume center.

BACKGROUND: Current guidelines discourage surgery for serous cystic neoplasms (SCN) of the pancreas, because of their benign character, slow growth, and excellent prognosis. Nevertheless, SCN continue to contribute up to 30% of resected cystic pancreatic lesions worldwide. METHODS: Spectrum of indications and outcomes of surgery were analysed in a retrospective series of 133 SCN at a single high-volume center in Germany between 2004 and 2019. RESULTS: Relevant symptoms justified surgery in 60% of patients with SCN, while 40% underwent surgery because of preoperative diagnostic uncertainty about suspected malignancy. There were 4 malignant SCN (3%). Ninety-day mortality was 0.75%, major morbidity - 15%, 10-year survival - 95%. Risks of malignant transformation and of postoperative mortality were similarly low. CONCLUSIONS: Surgery is reasonable and safe for symptomatic patients with SCN. Preoperative diagnostic uncertainty is the main reason for futile resections of benign asymptomatic SCN. Conservative management with close initial surveillance should be the first choice for this population. Surgery for supposed SCN without symptoms is justified only in carefully selected patients with suspected malignancy.

Risk factors for perforated marginal ulcers following pancreaticoduodenectomy and prospective analysis of marginal ulcer development.

BACKGROUND: Perforated marginal ulcers (PMUs) are a feared long-term complication following pancreaticoduodenectomy (PD), which always require relaparotomy compared to marginal ulcers. METHODS: First, we performed a retrospective chart review for all patients who underwent PD from 2007-2016 to identify incidence and risk factors associated with PMUs. Second, we analyzed follow up gastroscopies in all patients undergoing PD from 2007-2011 to identify the overall incidence of marginal ulcers. RESULTS: A total of 725 patients underwent PD in the retrospective study period. 17 patients (2.3%) suffered from PMU at a median postoperative time of 13 months. These patients were significantly younger (median age: 49 vs. 62 years; P=0.02) and suffered most often from chronic pancreatitis (P<0.001). Smoking and alcohol consumption were significantly more common (P=0.01 and P=0.023). An elevated level of carcinoembryonic antigen and chronic pancreatitis were identified as independent risk factors. Overall, 373 patients were enrolled for prospective analysis. Marginal ulcers occurred in 5-5.9% over a postoperative period of 5 years. CONCLUSIONS: Continuous treatment with proton-pump inhibitors for at least 5 years, immediate smoking cessation and follow-up gastroscopies are obligate for patients undergoing PD to avoid marginal ulcers and PMUs.

Anti-tumorigenic Effects of Emodin and Its' Homologue BTB14431 on Vascularized Colonic Cancer in a Rat Model.

OBJECTIVE: New drugs for cancer treatment are being sought worldwide. Therapeutic agents derived from natural substances can provide cost-efficient options. We evaluated the effect of emodin, an active natural anthraquinone derivate, and it's in-silico homologue the novel substance BTB14431 in vivo. METHOD: CC-531 colon cancer cells were implanted intraperitoneal (ip) and subcutaneous (sc) in 100 WAG/Rij rats. 28 days after tumor cell implantation, solid cancers were treated for 7 days by varying doses of BTB14431 (0.3 mg/kg body weight; 1.7 mg/kg) or emodin (2.5 mg/kg; 5 mg/kg). Treatment was applied either via an intravenous (iv) port catheter or by ip injection. Saline solution served as control. 21 days after final dose all animals were euthanized and ip tumor weight, sc tumor weight and animal body weight (bw) were determined by autopsy. Significant lower total tumor weight occurred after iv treatment with low dose BTB14431 (6.8 g; 90% confidence interval (CI) 5.3 - 8.2 g; p ≤ 0.01) and also low and high concentrations of emodin (9.4 g; CI 7.9 - 10.7 g; p ≤ 0.01 and 8.3 g; CI 7.6 - 9.3; p ≤ 0.01). Iv treatment by high dose BTB14431 did not lead to a decline in tumor weight. High dose ip treatment by emodin led to a lower overall (11.1 g; CI 10.1 - 13.8 g; p ≤ 0.01) and ip tumor weight (8.6 g; CI 6 - 10.4 g; p ≤ 0.01). Sc tumor weight was not affected. All other ip treatments did not result in changes of combined, ip or sc tumor weight. Bw decreased during iv treatment in all animals and increased after treatment was completed. Regain of bw was stronger in animals receiving low dose emodin. CONCLUSION: Our study shows promising anti-cancer properties of BTB14431 and supports the evidence regarding emodin as a natural antitumorigenic agent. Optimal dosing of iv emodin and especially BTB 14431 for maximal efficacy remains unclear and should be a subject of further research. 
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It's not all about the size-characteristics and risk factors for malignancy of mucinous cystic neoplasms of the pancreas.

BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas are rare mucin-producing cystic tumors. As they harbor malignant potential, surgical resection is frequently performed. Current guidelines recommend surgery in asymptomatic patients only for MCN exceeding 4 cm. The aim of this study was to identify radiological and clinical risk factors for malignancy in a single-center cohort of MCN. METHODS: All resected MCN from a single high-volume center between 2004 and 2019 were retrospectively analyzed. Patient characteristics, preoperative findings, histopathological results, and data on the postoperative course were recorded. Variables associated with malignancy were evaluated using χ2 and Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to model predictive capabilities of preoperative tumor marker levels. Furthermore uni- and multivariate logistic regression analysis were performed for binary variables. Survival time was plotted as Kaplan-Meier curves and evaluated by log-rank test. RESULTS: A total of 63 patients were included. Median age was 62 years; 51 (81.0%) of them were women; median tumor size was 3.5 cm (range, 0.5-18.5); 16 (25.4%) of tumors harbored invasive carcinoma and 13 presented intraepithelial dysplasia (20.6%); 7 (43.8%) invasive carcinomas were smaller than 4 cm. All malignant MCN were radiologically suspected of malignancy (calcifications, mural nodules, or wall thickness) preoperatively. Elevated levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were strongly associated with malignancy (odd's ratio 33.600; 7.000-161.270); P<0.001 and odd's ratio 19.250; 3.370-109.970; P<0.001). Other factors associated with malignancy were preoperative weight loss (P=0.015) and higher age (P=0.048). Tumor size, abdominal or back pain or jaundice showed no significant correlation to malignancy in our cohort. CONCLUSIONS: Malignant potential of MCN should not be underestimated and a close clinical and radiological follow-up is mandatory in all suspected cases. This is especially important for small lesions. Risk assessment should not rely only on tumor size but consider all clinical, radiological and laboratory findings of each case. Follow-up should be performed by experienced surgeons and radiologists in high volume centers for pancreatic surgery. Surgery should be performed in all cases in which malignancy is suspected.

Outcome Determining Factors of Intraductal Papillary Neoplasm of the Biliary Tract (IPNB)-a Single Center Survey and Analysis of Current Literature.

PURPOSE: Intraductal papillary neoplasms of the biliary tract (IPNB) are rare tumors originating from the bile duct epithelium. Metastatic disease of IPNB is extremely rare and only reported in a small number of cases worldwide. Due to this limitation in number, the treatment of IPNB mainly relies on retrospective case series. PATIENTS AND METHODS: We reported three cases of IPNB, one benign, one carcinoma with lymph node metastasis, and one case with histologically proven metachronous pulmonary metastasis. We correlated our findings with the existing data found in the literature. All patients underwent hemihepatectomy and complete tumor resection was achieved. RESULTS: Diagnosis of IPNB can be challenging due to varying presentation. The treatment of choice is surgical oncological resection in an early tumor stage. Long-term outcome highly depends on the underlying grade of dysplasia, multiplicity, and tumor-free margins. Aggressive tumor invasion is reported in up to 72% of cases in IPNB. Furthermore, the recurrence rate of IPNB is high with up to 22%. Further factors associated with an impaired survival are incomplete resection, lymph node involvement, and MUC1 expression. CONCLUSION: High potential for dysplasia and proof of invasive carcinoma upon diagnosis are hallmarks of IPNB. Metastatic disease in IPNB is reported only in small numbers. IPNB is an aggressive tumor entity with impaired long-term outcomes. A drawback for interpretation of current data is the fact that they rely on case series and reports and are not validated through more powerful randomized multicentric trials.

Riddle Me This: Acalculous Cholecystitis as an Unusual Complication of Immunoglobulin M Negative Mononucleosis.

Infectious mononucleosis is a common disease of the adolescent caused by the Epstein-Barr virus (EBV). We present a rare case of a male adult with acalculous cholecystitis due to infectious mononucleosis. A correct diagnosis was challenging due to a false negative antibody test. Laboratory values were significant for a marked lymphocytosis and an early Immunoglobulin G (IgG) response without initial Immunoglobulin M (IgM) elevation. However, IgM antibodies were elevated two weeks later. Symptoms resolved quickly under symptomatic therapy. Antibody level patterns in asplenic patients with infectious mononucleosis are characterized by an atypical course with a delayed rise in IgM antibodies, which complicates the correct diagnosis of an EBV-induced acalculous cholecystitis.

Dose-dependent role of novel agents emodin and BTB14431 in colonic cancer treatment in rats.

BACKGROUND: BTB14431 is an in silico homolog to emodin. Both were found to possess anti-tumor effects in vitro. The aim of this work was to analyze the tumor suppressing effects of both molecules in an intraperitoneal (ip) and intravenous (iv) treated rat model (WAG-Rij). METHODS: A tumor cell suspension (CC531) was applied at the cecum after laparotomy and at the back. The rats where treated twice a day over 1 week with BTB14431, emodin and isotone sodium chloride solution (control). Treatment was applied iv or ip in a variety of dosages. Peripheral blood samples were taken before tumor application and on day 7. Twenty-one days after the last day of therapy animals were euthanized and tumor growth was evaluated. RESULTS: Data showed an insignificant decrease of tumor growth after iv and ip treatment with low doses of BTB14431 and emodin. Differential blood analysis showed apoptosis. Increased doses of emodin clearly raised mortality rate. CONCLUSIONS: Apoptosis was verified but no tumor-suppressing effects could be observed for iv and ip treatment with both agents in contrast to in vitro studies in our model. Establishing a successful ip treatment model for emotion and BTB14331 requires further studies.

The Physiological Incubation Biosimulator (PIBS): An Improved Ex Vivo Experimental Setup for the Mechanical Stability of Biological Sealants in Surgical Procedures.

BACKGROUND: Tissue-bound fibrin sealants are used in a wide array of surgical procedures. The microenvironmental interaction between sealant and application site is often poorly evaluated due to a lack of suitable experimental models. METHODS: A physiological incubation biosimulator (PIBS) was developed to test biological sealants in an ex vivo setup under physiological conditions comparable to the microenvironment at application site (temperature, humidity, pressure). PIBS was validated by a study on the effectiveness of TachoSil for leak closure at pancreatic resection sites. Defined defects in a thoracic membrane of porcine origin were sealed by TachoSil. Integrity of the sealing was tested in the presence of active pancreatic fluid over 60 minutes. Heat-inactivated pancreatic fluid and electrolyte solution served as controls. The time to leakage was recorded and experimental groups were analyzed by Kaplan-Meier analysis. RESULTS: PIBS produced reliable results. TachoSil lead to a leakage rate of 96% after incubation with active pancreatic fluid (p = 34), which was significantly higher compared with heat-inactivated pancreatic fluid (p = 34, 52%) or electrolyte solution (p = 20, 19%). CONCLUSION: PIBS is an effective tool to evaluate microenvironmental effects on the adhesive strength of biomaterials. Tissue sealing effect of TachoSil is diminished in a "pancreatic" microenvironment rich with pancreatic enzymes. Our results might therefore explain the reason of the findings of randomized controlled trials recently published on this subject.