Concomitant Cervical and Anal Screening for Human Papilloma Virus (HPV): Worth the Effort or a Waste of Time?

Background: This study represents a follow-up analysis of the (ANGY) study.

Methods: This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic, representing the study cohort for this follow-up study.

Ondansetron for Low Anterior Resection Syndrome (LARS): A Double-Blind, Placebo-Controlled, Cross-Over, Randomized Study.

Objective: The aim of the study was to examine the efficacity and safety of ondansetron, a serotonin receptor antagonist, to treat patients with low anterior resection syndrome (LARS).

Background: LARS after rectal resection is common and debilitating. Current management strategies include behavioral and dietary modifications, physiotherapy, antidiarrheal drugs, enemas, and neuromodulation, but the results are not always satisfactory.

[Anal cancer screening. A decade's experience of a consultation in a tertiary centre].

Anal cancer is a disease with a low but gradually increasing incidence, especially in developed countries. Most of these cancers are caused by the HPV. In Switzerland, more than 70 % of the sexually active population is infected with HPV at least once, making it the most common sexually transmitted disease.

Rate of stoma formation following damage-control surgery for severe intra-abdominal sepsis: a single-centre consecutive case series.

Background: Severe intra-abdominal sepsis (IAS) is associated with high mortality and stoma rates. A two-stage approach with initial damage-control surgery (DCS) and subsequent reconstruction might decrease stoma and mortality rates but requires standardization.

Methods: A standardized two-stage damage-control algorithm for IAS was implemented in April 2016 and applied systematically.

Elective Surgery for Diverticulitis in Swiss Hospitals.

To assess current management of diverticulitis in Switzerland. Prospective observational study of diverticulitis management and outcomes in surgical departments over a 3-month time period. Hospital category was graded according to the Swiss Medical Association (FMH) as: U: University; A: Cantonal; B: Regional; P: Private.

Contemporary snapshot of tumor regression grade (TRG) distribution in locally advanced rectal cancer: a cross sectional multicentric experience.

Pre-operative chemoradiotherapy (CRT) followed by surgical resection is still the standard treatment for locally advanced low rectal cancer. Nowadays new strategies are emerging to treat patients with a complete response to pre-operative treatment, rendering the optimal management still controversial and under debate. The primary aim of this study was to obtain a snapshot of tumor regression grade (TRG) distribution after standard CRT.

Mechanistic Target of Rapamycin Inhibitors in Renal Cell Carcinoma: Potential, Limitations, and Perspectives.

Several elements highlight the importance of the mechanistic target of rapamycin (mTOR) in the biology of renal cell carcinoma (RCC). mTOR signaling pathway is indeed frequently activated in RCC, inducing cancer cell proliferation and survival. In addition, mTOR promotes tumor angiogenesis and regulates the expression of hypoxia-inducible factors that play an important role in a subset of RCC.

Rebound pathway overactivation by cancer cells following discontinuation of PI3K or mTOR inhibition promotes cancer cell growth.

Whilst effects of anti-cancer drugs have been thoroughly explored, little is known about the repercussion of drug cessation. However, this has important clinical relevance since several clinical protocols such as intermittent drug scheduling lead to frequent drug discontinuation. In this study, we have thus investigated the consequences of withdrawal of agents that target the PI3K/AKT/mTOR signaling pathway in cancer cells.

[Not Available].

Surgical treatment of chronic inflammatory bowel disease Abstract. Surgery is an important mainstay in the treatment of inflammatory bowel disease. Despite considerable progress in anti-inflammatory treatment approaches, two thirds of patients with Crohn's Disease will need surgery during their lifetime.

Evolving Significance and Future Relevance of Anti-Angiogenic Activity of mTOR Inhibitors in Cancer Therapy.

mTOR inhibitors have demonstrated remarkable anti-tumor activity in experimental models, mainly by reducing cancer cell growth and tumor angiogenesis. Their use in cancer patients as monotherapy has, however, generated only limited benefits, increasing median overall survival by only a few months. Likewise, in other targeted therapies, cancer cells develop resistance mechanisms to overcome mTOR inhibition.

Fine-Tuning Tumor Endothelial Cells to Selectively Kill Cancer.

Tumor endothelial cells regulate several aspects of tumor biology, from delivering oxygen and nutrients to shaping the immune response against a tumor and providing a barrier against tumor cell dissemination. Accordingly, targeting tumor endothelial cells represents an important modality in cancer therapy. Whereas initial anti-angiogenic treatments focused mainly on blocking the formation of new blood vessels in cancer, emerging strategies are specifically influencing certain aspects of tumor endothelial cells.

Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity.

Targeting mTORC1 has been thoroughly explored in cancer therapy. Following encouraging preclinical studies, mTORC1 inhibitors however failed to provide substantial benefits in cancer patients. Several resistance mechanisms have been identified including mutations of mTOR and activation of alternate proliferation pathways.

Acidic tumor microenvironment abrogates the efficacy of mTORC1 inhibitors.

Background: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study.

Acidic pH reduces VEGF-mediated endothelial cell responses by downregulation of VEGFR-2; relevance for anti-angiogenic therapies.

Anti-angiogenic treatments targeting the vascular endothelial growth factor or its receptors have shown clinical benefits. However, impact on long-term survival remains limited. Solid tumors display an acidic microenvironment that profoundly influences their biology.

[Multidisciplinary treatment of locally advanced rectal cancer].

Treatment of patients with locally advanced rectal cancer remains challenging. Preoperative imaging with pelvic MRI allows to identify patients for multimodal treatment including induction chemothe- rapy or neoadjuvant radio-chemotherapy and an extended surgical resection. With multidisciplinary approach and an experienced team, excellent oncologic results may be achieved, as well as a good function and quality of life, even with preservation of the anus in the majority of patients.

Targeting carbonic anhydrase IX improves the anti-cancer efficacy of mTOR inhibitors.

The inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) by chemical inhibitors, such as rapamycin, has demonstrated anti-cancer activity in preclinical and clinical trials. Their efficacy is, however, limited and tumors eventually relapse through resistance formation. In this study, using two different cancer mouse models, we identify tumor hypoxia as a novel mechanism of resistance of cancer cells against mTORC1 inhibitors.

PI3K and AKT: Unfaithful Partners in Cancer.

The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway regulates multiple cellular processes. An overactivation of the pathway is frequently present in human malignancies and plays a key role in cancer progression. Hence, its inhibition has become a promising approach in cancer therapy.

PGE2-induced colon cancer growth is mediated by mTORC1.

The inflammatory prostaglandin E2 (PGE2) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized.