Microsurgical Lymph Node Dissection for Metastatic Asymptomatic C-Cell Carcinoma

In persistent, clinically inapparent medullary thyroid carcinoma, microsurgical dissection of all lymph node compartments of the neck was performed. Between August 1988 and September 1991, 28 cases (mean age 43.3 years) were treated with 38 surgical interventions. Twenty patients had the sporadic form and eight patients the familial form. Unilateral neck dissection resulted in normalization of serum calcitonin (CT) levels even after pentagastrin stimulation in two patients whereas 16 patients exhibited abnormal CT stimulation tests. Eight of ten patients who had bilateral neck dissections had positive pentagastrin test results after surgery. The main postoperative complications included loss of local cutaneous sensation, generally temporary, and unilateral recurrent laryngeal nerve paralysis

Chemoembolization of the Lung Improves Tumor Control in a Rat Model

ABSTRACT Purpose: The novel method of organ-specific drug application we present here is unilateral chemoembolization of the lung by injecting the pulmonary artery with degradable starch microspheres and cytotoxic drugs to improve tumor control in lung metastases. Experimental Design: In a solitary metastasis rat model (CC531 adenocarcinoma), we studied the clinical and histological tumor response as well as subacute toxicity of the lung. Fourteen days after tumor induction, animals were randomized into five groups. Groups I and II served as controls. Group III received carboplatin i.v. (45 mg/kg). Isolated lung perfusion with buffered starch solution and carboplatin (15 mg/kg) was installed in group IV. Chemoembolization with carboplatin (15 mg/kg) was performed in group V. Results: Seven days later, the difference in the tumor volume before and after treatment was ؉422 mm 3 (؎226) in group I, ؉697 mm 3 (؎423) in group II, ؉70 mm 3 (؎31) in group III, ؊8 mm 3 (؎17) in group IV, and ؊17 mm 3 (؎16) in group V (P < 0.05 groups IV and V versus groups I, II, and III). No pleural spread was observed in groups IV and V. Histologically, the area of tumor necrosis was largest in group IV. Mild alveolar cell hyperplasia, pulmonary edema, and hemorrhage without subacute fibrotic changes were noted in all groups. Conclusion: This is the first study to perform chemoembolization of the lung. Compared with i.v. therapy, chemoembolization was more effective without serious toxicity. Its efficacy was comparable with that of isolated lung perfusion but less stressful for a possible clinical application

An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types

Wiskott–Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis

Effect of Network Architecture on Synchronization and Entrainment Properties of the Circadian Oscillations in the Suprachiasmatic Nucleus

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker. The SCN receives light signals from the retina and controls peripheral circadian clocks (located in the cortex, the pineal gland, the liver, the kidney, the heart, etc.). This hierarchical organization of the circadian system ensures the proper timing of physiological processes. In each SCN neuron, interconnected transcriptional and translational feedback loops enable the circadian expression of the clock genes. Although all the neurons have the same genotype, the oscillations of individual cells are highly heterogeneous in dispersed cell culture: many cells present damped oscillations and the period of the oscillations varies from cell to cell. In addition, the neurotransmitters that ensure the intercellular coupling, and thereby the synchronization of the cellular rhythms, differ between the two main regions of the SCN. In this work, a mathematical model that accounts for this heterogeneous organization of the SCN is presented and used to study the implication of the SCN network topology on synchronization and entrainment properties. The results show that oscillations with larger amplitude can be obtained with scale-free networks, in contrast to random and local connections. Networks with the small-world property such as the scale-free networks used in this work can adapt faster to a delay or advance in the light/dark cycle (jet lag). Interestingly a certain level of cellular heterogeneity is not detrimental to synchronization performances, but on the contrary helps resynchronization after jet lag. When coupling two networks with different topologies that mimic the two regions of the SCN, efficient filtering of pulse-like perturbations in the entrainment pattern is observed. These results suggest that the complex and heterogeneous architecture of the SCN decreases the sensitivity of the network to short entrainment perturbations while, at the same time, improving its adaptation abilities to long term changes

Pylorus resection versus pylorus preservation in pancreatoduodenectomy (PyloResPres): study protocol and statistical analysis plan for a German multicentre, single-blind, surgical, registry-based randomised controlled trial

INTRODUCTION Partial pancreatoduodenectomy (PD) is the treatment of choice for various benign and malignant tumours of the pancreatic head or the periampullary region. For reconstruction of the gastrointestinal passage, two stomach-preserving PD variants exist: pylorus preservation PD (ppPD) or pylorus resection PD (prPD) with preservation of the stomach. In pancreatic surgery, delayed gastric emptying (DGE) remains a serious complication after PD with an incidence varying between 4.5% and 45%, potentially delaying hospital discharge or further treatment, for example, adjuvant chemotherapy. Evidence is lacking to assess, which variant of PD entails fewer postoperative DGE. METHODS AND ANALYSIS The protocol of a large-scale, multicentre, pragmatic, two-arm parallel-group, registry-based randomised controlled trial (rRCT) using a two-stage group-sequential design is presented. This patient-blind rRCT aims to demonstrate the superiority of prPD over ppPD with respect to the overall incidence of DGE within 30 days after index surgery in a German real-world setting. A total of 984 adults undergoing elective PD for any indication will be randomised in a 1:1 ratio. Patients will be recruited at about 30 hospitals being members of the StuDoQ|Pancreas registry established by the German Society of General and Visceral Surgery. The postoperative follow-up for each patient will be 30 days. The primary analysis will follow an intention-to-treat approach and applies a binary logistic random intercepts model. Secondary perioperative outcomes include overall severe morbidity (Clavien-Dindo classification), blood loss, 30-day all-cause mortality, postoperative hospital stay and operation time. Complication rates and adverse events will be closely monitored. ETHICS AND DISSEMINATION This protocol was approved by the leading ethics committee of the Medical Faculty of the Ludwig-Maximilians-Universität, Munich (reference number 19-221). The results will be published in a peer-reviewed journal and presented at international conferences. Study findings will also be disseminated via the website (http://www.dgav.de/studoq/pylorespres/). TRIAL REGISTRATION NUMBER DRKS-ID: DRKS00018842