Mechanisms of biliary carcinogenesis: A pathogenetic multi-stage cascade towards cholangiocarcinoma

Carcinomas of the biliary tract are rare cancers developing from the epithelial or blast-like cells lining the bile ducts. A variety of known predisposing factors and recent experimental modelsof biliary carcinogenesis (e.g., infection with the liver fluke Opisthorchis viverrini, models of chemically induced carcinogenesis and experimental models of pancreaticobiliary maljunction) have elucidated different stages of this complex system of biliary tumorigenesis. Chronic inflammatory processes, generation of active oxygen radicals, altered cellular detoxificationmechanisms, activation of oncogenes, functional loss of tumor-suppressor genes and dysregulation of cell proliferation and cell apoptotic mechanisms have been identified as important contributorsin the development of cholangiocarcinomas. In this review, the known mechanisms involved in the carcinogenesis of biliary epithelium are addressed. We will divide the topic into four stages: 1) Predisposition and risk factors of biliary cancer. 2) Genotoxic events and alterations leading to specific DNA damage and mutation patterns. 3) Dysregulation of DNA repair mechanisms and apoptosis, permitting survival of mutated cells and 4) Morphological evolution from premalignant biliary lesions to cholangiocarcinoma. Finally, established and hypothetical future therapeutic strategies directed towards specific pathogenetic events during biliary carcinogenesis will be addresse

The suprapubic approach for laparoscopicappendectomy

Background: Because it produces superior cosmetic results, patients prefer laparoscopic appendectomy over open appendectomy. We developed two alternative laparoscopic routes of access to the abdominal cavity for appendectomy that use suprapubic incisions placed below the line of pubic hair. We then compared the results for these three different modes of access. Methods: Operative characteristics, morbidity, outcome, and patient preference regarding three different approaches to laparoscopic appendectomy were compared in a retrospective study. In addition, a group of 24 healthy women were surveyed by questionnaire about their preferred technique and expected cosmetic results. Results: Between January 1997 and August 2000, 149 patients underwent laparoscopic appendectomy and were assigned to undergo one of the three techniques. Operative results, morbidity, and hospital stay were similar. Twenty-five percent of patients submitted to technique 1 (no suprapubic trocars) were satisfied with their method, vs 54% of patients with technique 2 (one suprapubic port, angled working trocars) and 100% of patients with technique 3 (two suprapubic parallel trocars). Almost all patients (92% of those who had technique 1 and 100% of those who had techniques 2 and 3) chose the standard laparoscopic access as the cosmetically least attractive method. All of the healthy controls we interviewed preferred technique 3. Conclusion: The placement of suprapubic trocars improves the surgeon's working position during laparoscopic appendectomy. A laparoscopic approach using two suprapubic trocars yields the best cosmetic results in the opinion of the majority of patients and healthy interviewee

Standard surgical treatment in pancreatic cancer

Pancreatic cancer is the third leading neoplasm of the gastrointestinal system and has a dismal prognosis. The majority of patients are no more suitable for resection at time of diagnosis due to early development of distant metastases or major infiltrations of adjacent structures. However, due to the resistance of pancreatic cancers against chemoradiation, curative resection represents the only therapy with a potential for cure. For the surgical treatment of pancreatic head cancer, the classical Whipple operation is still the standard procedure but during the last two decades, pylorus-preserving duodenopancreatectomy has been evolved as a more conservative procedure in order to omit the consequences of partial gastrectomy. For cancer of the pancreatic body and tail, distal pancreatectomy or total pancreatectomy represent the current standard treatment. More radical methods like regional pancreatectomy and resection with extended lymph node dissection have failed so far to demonstrate any improvements in long-term survival compared to the standard types of resection. To further improve the treatment of pancreatic cancer, prospectively randomised trials are needed to compare these extended surgical procedures with the standard types of resectio

Prophylactic Glycine Administration Attenuates Pancreatic Damage and Inflammation in Experimental Acute Pancreatitis

Background/Aims: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. Methods: To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. Results: Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. Conclusions: Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP

Dissipative Dynamics of a Josephson Junction In the Bose-Gases

The dissipative dynamics of a Josephson junction in the Bose-gases is considered within the framework of the model of a tunneling Hamiltonian. The effective action which describes the dynamics of the phase difference across the junction is derived using functional integration method. The dynamic equation obtained for the phase difference across the junction is analyzed for the finite temperatures in the low frequency limit involving the radiation terms. The asymmetric case of the Bose-gases with the different order parameters is calculated as well

Evidence Map of Pancreatic Surgery–A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS)

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30, 860 articles reviewed, 328 randomized controlled trials on 35, 600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%–1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%–61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%–80%) for distal pancreatectomy. Conclusion: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers. © 2021 The Author

Study of the lineshape of the chi(c1) (3872) state

A study of the lineshape of the chi(c1) (3872) state is made using a data sample corresponding to an integrated luminosity of 3 fb(-1) collected in pp collisions at center-of-mass energies of 7 and 8 TeV with the LHCb detector. Candidate chi(c1)(3872) and psi(2S) mesons from b-hadron decays are selected in the J/psi pi(+)pi(-) decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the chi(c1 )(3872) and psi(2S) states, Delta m, and the width of the chi(c1 )(3872) state, Gamma(Bw), are determined to be (Delta m=185.598 +/- 0.067 +/- 0.068 Mev,)(Gamma BW=1.39 +/- 0.24 +/- 0.10 Mev,) where the first uncertainty is statistical and the second systematic. Using a Flatte-inspired model, the mode and full width at half maximum of the lineshape are determined to be (mode=3871.69+0.00+0.05 MeV.)(FWHM=0.22-0.04+0.13+0.07+0.11-0.06-0.13 MeV, ) An investigation of the analytic structure of the Flatte amplitude reveals a pole structure, which is compatible with a quasibound D-0(D) over bar*(0) state but a quasivirtual state is still allowed at the level of 2 standard deviations