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

Das pT4-Pankreaskarzinom: Chirurgische und multimodale Behandlung

Zusammenfassung: Grundlagen: Die Resektion, unterstützt durch multimodale Therapieschemata, gilt auch beim T4-Pankreaskarzinom als einzige kurative Therapie. Methodik: Beim T4-Pankreaskarzinom muß häufig ein erweitertes Resektionsverfahren gewählt werden, das eine En-bloc-Entfernung des Tumors erlaubt und heute mit einer niederen Morbidität und Moralität vorgenommen werden kann. Der Stellenwert der Lymphknotendissektion bei diesen lokal fortgeschrittenen Pankreaskarzinomen ist nicht geklärt. Die hohe Lokalrezidivrate kann eventuell durch eine radikalere Lymphknotendissektion zusammen mit einer präoperativen, intraoperativen oder postoperativen kombinierten Chemotherapie verbessert werden. Ergebnisse: Die Ergebnisse multimodaler Therapieschemata zur Behandlung des Pankreaskarzinoms werden vorgestellt und der Stellenwert der einzelnen potentiell kurativen und palliativen Modalitäten diskutiert. Schlußfolgerungen: Obwohl der Einfluß auf Lokalrezidivraten und Überleben beim T4-Pankreaskarzinom noch nicht geklärt ist, scheint eine multimodale Behandlung bei der Gesamtgruppe der Patienten mit Pankreaskarzinom diesbezüglich bessere Resultate zu erzielen. Diese Resultate werden in Zukunft noch in prospektiv randomisiert durchgeführten Multicenter-Studien geklärt werde

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

Repetitive spinal motor neuron discharges following single transcranial magnetic stimulation: relation to dexterity

Transcranial magnetic stimulation allows to study the properties of the human corticospinal tract non-invasively. After a single transcranial magnetic stimulus, spinal motor neurons (MNs) sometimes fire not just once, but repetitively. The biological significance of such repetitive MN discharges (repMNDs) is unknown. To study the relation of repMNDs to other measures of cortico-muscular excitability and to physiological measures of the skill for finely tuned precision movements, we used a previously described quadruple stimulation (QuadS) technique (Z'Graggen et al. 2005) to quantify the amount of repMNDs in abductor digiti minimi muscles (ADMs) on both sides of 20 right-handed healthy subjects. Skillfulness for finger precision movements of both hands was assessed using a finger tapping task. In 16 subjects, a follow-up examination was performed after training of either precision movements (n=8) or force (n=8) of the left ADM. The size of the QuadS response (amplitude and area ratios) was greater in the dominant right hand than in the left hand (QuadS amplitude ratio: 47.1±18.1 versus 37.7±22.0%, Wilcoxon test: P<0.05; QuadS area ratio: 49.7±16.2% versus 36.9±23.0%, Wilcoxon test: P<0.05), pointing to a greater amount of repMNDs. Moreover, the QuadS amplitude and area increased significantly after finger precision training, but not after force training. This increase of repMNDs correlated significantly with the increase in performance in the finger tapping task. Our results demonstrate that repMNDs are related to handedness and therefore probably reflect supraspinal excitability differences. The increase of repMNDs after skills training but not after force training supports the hypothesis of a supraspinal origin of repMND

Traumatic brain injury in the elderly after a skiing accident: A retrospective cohort study in a level 1 emergency department in Switzerland.

BACKGROUND Skiing is a very popular sport worldwide, with increasing trends over the past decades. This study aimed to evaluate the importance of traumatic brain injury (TBI), especially in the elderly, after a ski accident, and to describe its short-term repercussions. METHODOLOGY Patients were analyzed who were admitted to our neurotrauma center from 2012-2018 after a head trauma while skiing. Three different age groups were differentiated and analyzed for the severity of TBI depending on the initial Glasgow Coma Scale as the primary outcome and as secondary outcomes need and type of surgery, Glasgow Outcome Score, preexisting use of anticoagulant or antiplatelet drugs, time to presentation, and pattern of brain injury. TBI severity was adjusted to the time to initial medical consultation. RESULTS No significant difference in TBI severity was found when comparing the middle (>29-54) and older (≥54) age groups to the reference group <30 years (OR:0.45, p = 0.127; OR:0.46, p = 0.17). Acute subdural hemorrhage was present in 21.2% of the ≥55 group and 14.5% of the 30-54 age group, compared to 12.8% of the youngest group (p = <0.001). Overall, 39.4% of the patients in the ≥55 group and 8.1% of the 30-54 age group presented with chronic subdural hemorrhage, whereas none of the youngest patients did (p = <0.001). CONCLUSION No differences were observed in terms of TBI severity between age groups after acute trauma. Nonetheless, a different pattern of head injury after TBI in older patients was demonstrated. Accordingly, the management differs for these TBIs compared to those of younger patients

Muscle velocity recovery cycles in myopathy.

OBJECTIVE To understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies. METHODS 42 patients with quantitative electromyography (qEMG) and biopsy or genetic verified myopathy and 42 healthy controls were examined with qEMG, MVRC and RAMP, all recorded from the anterior tibial muscle. RESULTS There were significant differences in the motor unit potential (MUP) duration, the early and late supernormalities of the MVRC and the RAMP latencies in myopathy patients compared to controls (p < 0.05 apart from muscle relatively refractory period (MRRP)). When dividing into subgroups, the above-mentioned changes in MVRC and RAMP parameters were increased for the patients with non-inflammatory myopathy, while there were no significant changes in the group of patients with inflammatory myopathy. CONCLUSIONS The MVRC and RAMP parameters can discriminate between healthy controls and myopathy patients, more significantly for non-inflammatory myopathy. MVRC differences with normal MRRP in myopathy differs from other conditions with membrane depolarisation. SIGNIFICANCE MVCR and RAMP may have a potential in understanding disease pathophysiology in myopathies. The pathogenesis in non-inflammatory myopathy does not seem to be caused by a depolarisation of the resting membrane potential but rather by the change in sodium channels of the muscle membrane

TME quality in rectal cancer surgery

<p>Abstract</p> <p>Background</p> <p>The concept of total mesorectal excision has revolutionised rectal cancer surgery. TME reduces the rate of local recurrence and tumour associated mortality. However, in clinical trials only 50% of the removed rectal tumours have an optimal TME quality. Patients: During a period of 36 months we performed 103 rectal resections. The majority of patients (76%; 78/103) received an anterior resection. The remaining patients underwent either abdominoperineal resection (16%; 17/103), Hartmann's procedure (6%; 6/103) or colectomy (2%; 2/103).</p> <p>Results</p> <p>In 90% (93/103) TME quality control could be performed. 99% (92/93) of resected tumours had optimal TME quality. In 1% (1/93) the mesorectum was nearly complete. None of the removed tumours had an incomplete mesorectum. In 98% (91/93) the circumferential resection margin was negative. Major surgical complications occurred in 17% (18/103). 5% (4/78) of patients with anterior resection had anastomotic leakage. 17% (17/103) developed wound infections. Mortality after elective surgery was 4% (4/95).</p> <p>Conclusion</p> <p>Optimal TME quality results can be achieved in all stages of rectal cancer with a rate of morbidity and mortality comparable to the results from the literature. Future studies should evaluate outcome and local recurrence in accordance to the degree of TME quality.</p