Liver surgery in cirrhosis and portal hypertension

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis

Ileo-right hemi-colonic cervical pull-up on a non-supercharged ileocolic arterial pedicle: A technical and case report

Esophageal reconstruction can be challenging when stomach and colon are not anatomically intact and their use as esophageal substitutes is therefore limited. Innovative individual approaches are then necessary to restore the intestinal passage. We describe a technique in which a short stump of the right hemicolon and 25 cm of ileum on a long, non-supercharged, fully mobilized ileocolic arterial pedicle were used for esophageal reconstruction to the neck. In this case, a 65 year-old male patient had accidentally indigested hydrochloric acid which caused necrosis of his upper digestive tract. An emergency esophagectomy, gastrectomy, duodenectomy, pancreatectomy and splenectomy had been performed in an outside hospital. A cervical esophagostomy and a biliodigestive anastomosis had been created and a jejunal catheter for enteral feeding had been placed. After the patient had recovered, a reconstruction of his food passage via the left and transverse colon failed for technical reasons due to an intraoperative necrotic demarcation of the colon. Our team then faced the situation that only a short stump of the right hemi-colon was left in situ when the patient was referred to our center. After intensified nutritional therapy, we reconstructed this patient's food passage with the right hemicolon-approach described herein. After treatment of a postoperative pneumonia, the patient was discharged from hospital on the 26th postoperative day in a good clinical condition on an oral-only diet. In conclusion, individual approaches for long-segment reconstruction of the esophagus can be technically feasible in experienced hands. They do not always require arterial supercharging or free intestinal transplantation

Resection of oesophageal and oesophagogastric junction cancer liver metastases — a summary of current evidence

Purpose Metastatic oesophageal cancer is commonly considered as a palliative situation with a poor prognosis. However, there is increasing evidence that well-selected patients with a limited number of liver metastases (ECLM) may benefit from a multimodal approach including surgery. Methods A systematic review of the current literature for randomized trials, retrospective studies, and case series with patients undergoing hepatectomies for oesophageal and oesophagogastric junction cancer liver metastases was conducted up to the 31st of August 2021 using the MEDLINE (PubMed) and Cochrane Library databases. Results A total of 661 articles were identified. After removal of duplicates, 483 articles were screened, of which 11 met the inclusion criteria. The available literature suggests that ECLM resection in patients with liver oligometastatic disease may lead to improved survival and even long-term survival in some cases. The response to concomitant chemotherapy and liver resection seems to be of significance. Furthermore, a long disease-free interval in metachronous disease, low number of liver metastases, young age, and good overall performance status have been described as potential predictive markers of outcome for the resection of liver metastases. Conclusion Surgery may be offered to carefully selected patients to potentially improve survival rates compared to palliative treatment approaches. Studies with standardized patient selection criteria and treatment protocols are required to further define the role for surgery in ECLM. In this context, particular consideration should be given to neoadjuvant treatment concepts including immunotherapies in stage IVB oesophageal and oesophagogastric junction cancer

Next-generation sequencing of the CHO cell transcriptome

Meeting abstract from 22nd European Society for Animal Cell Technology(ESACT) Meeting on Cell Based Technologies Vienna, Austria. 15-18 May 2011(VLID)90656

Visualization of Vascular Perfusion of Human Pancreatic Cancer Tissue in the CAM Model and Its Impact on Future Personalized Drug Testing

Although significant improvements have been made in the treatment of pancreatic cancer, its prognosis remains poor with an overall 5-year survival rate of less than 10%. New experimental approaches are necessary to develop novel therapeutics. In this study, the investigation of pancreatic cancer tissue growth in the chorioallantoic membrane (CAM) model and the subsequent use of indocyanine green (ICG) injections for the verification of intratumoral perfusion was conducted. ICG was injected into the CAM vasculature to visualize the perfusion of the tumor tissue. The presence of metastasis was investigated through PCR for the human-specific ALU element in the liver of the chicken embryo. Additionally, the usage of cryopreserved pancreatic tumors was established. Intratumoral perfusion of tumor tissue on the CAM was observed in recently obtained and cryopreserved tumors. ALU-PCR detected metastasis in the chick embryos’ livers. After cryopreservation, the tissue was still vital, and the xenografts generated from these tumors resembled the histological features of the primary tumor. This methodology represents the proof of principle for intravenous drug testing of pancreatic cancer in the CAM model. The cryopreserved tumors can be used for testing novel therapeutics and can be integrated into the molecular tumor board, facilitating personalized tumor treatment

Gene Expression Signatures of a Preclinical Mouse Model during Colorectal Cancer Progression under Low-Dose Metronomic Chemotherapy

Simple Summary Colorectal cancer is one of the most frequent types of cancer world-wide, leading to over 500,000 cancer-related deaths each year. Although many primary colorectal cancer patients can be cured by surgery, up to 60% will develop metastases. Chemotherapeutic strategies are well-established, but finally often lead to chemo-resistance and tumor relapse. A specific chemotherapeutic approach is low dose metronomic (LDM) therapy, which is based on a constant administration of low doses of a chemotherapeutic compound instead of high-dose pulses, which are often a huge burden for patients and also may induce rapid resistance. However, the molecular mechanism of LDM chemotherapy is not fully understood. Our study therefore aims at identifying gene signatures of colorectal cancer progression under LDM chemotherapy which eventually provides new potential biomarkers for therapeutic interventions. Abstract Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy

Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis

Classic tumor therapy, consisting of cytotoxic agents and/or targeted therapy, has not overcome therapeutic limitations like poor risk genetic parameters, genetic heterogeneity at different metastatic sites or the problem of undruggable targets. Here we summarize data and trials principally following a completely different treatment concept tackling systems biologic processes: the principle of communicative reprogramming of tumor tissues, i.e., anakoinosis(ancient greek for communication), aims at establishing novel communicative behavior of tumor tissue, the hosting organ and organism via re-modeling gene expression, thus recovering differentiation, and apoptosis competence leading to cancer control – in contrast to an immediate, “poisoning” with maximal tolerable doses of targeted or cytotoxic therapies. Therefore, we introduce the term “Master modulators” for drugs or drug combinations promoting evolutionary processes or regulating homeostatic pathways. These “master modulators” comprise a broad diversity of drugs, characterized by the capacity for reprogramming tumor tissues, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs etc., or for example differentiation inducing therapies. Data on 97 anakoinosis inducing schedules indicate a favorable toxicity profile: The combined administration of master modulators, frequently (with poor or no monoactivity) may even induce continuous complete remission in refractory metastatic neoplasia, irrespectively of the tumor type. That means recessive components of the tumor, successively developing during tumor ontogenesis, are accessible by regulatory active drug combinations in a therapeutically meaningful way. Drug selection is now dependent on situative systems characteristics, to less extent histology dependent. To sum up, anakoinosis represents a new substantive therapy principle besides novel targeted therapies

The Effects of Violent Images in Television News Coverage on children An Analysis of the German childrens’ news programme ‘logo!’

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