Daphne Hompes

The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: A comparative study

Oxaliplatin and Mitomycin C (MMC) are both suitable as intraperitoneal chemotherapy agents in HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer (CRC).

Soft tissue sarcoma: an update on systemic treatment options for patients with advanced disease.

Sarcomas are a group of rare solid tumours arising from mesenchymal or connective tissue. This review focuses on soft tissue sarcoma and covers general topics such as the epidemiology, age distribution, site of disease, histogenesis, histological subtypes, prognosis and outcome of treatment. In more detail, the article reviews current systemic treatment standards and selected adverse events of agents such as doxorubicin, ifosfamide, trabectedin and pazopanib, and briefly highlights some drugs that are used off-label in specific subtypes of sarcoma.

Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer

OBJECTIVE AND BACKGROUND This review describes the extent, frequency and clinical importance of Bevacizumab(BV)-related serious adverse events (SAE) after surgery, during or after chemotherapy with BV in patients with metastatic colorectal cancer (mCRC). METHODS Detailed PubMed search in November 2009. RESULTS Addition of BV to first- or second-line chemotherapy in patients with mCRC results in a statistically significant benefit in OS, PFS and RR. Addition of BV to chemotherapy causes no clinically relevant aggravation of SAE and seems safe with the primary tumor still in situ. The risk of emergency surgery due to BV-related SAE is estimated 2.0%. SAE rate is low if a time to surgery of 5-6 weeks is respected. The majority of SAE are wound healing complications. Bleeding and GI perforation occur infrequently, even following major surgery after BV-treatment. Major surgery during the course of BV-treatment results in an SAE rate of 1.3-2.7%. Postoperatively, a period of minimally 28 days should be respected before starting BV. CONCLUSION Reported rates of BV-related SAE in relationship to surgery are low.

Radiofrequency ablation as a treatment tool for liver metastases of colorectal origin

Abstract At diagnosis 10–25% of patients with colorectal liver metastases (CRLM) present as resectable disease. Liver resection is the gold standard treatment, resulting in a 5-year overall survival (OS) of 22–58%, local recurrence rates of 1.2–10.4% and a perioperative mortality of less than 5%. Multiple attempts have been made to assess the possible contribution of radiofrequency ablation (RFA) to improve OS and progression-free survival (PFS) in patients with unresectable colorectal liver metastases. The aim of this paper is to review the RFA literature in the setting of colorectal liver metastases: RFA with and without chemotherapy, RFA with and without resection, RFA for solitary unresectable CRLM, surgical and percutaneous imaging-guided RFA, RFA compared with chemotherapy. The reported OS, PFS, local recurrence rates, morbidity and mortality in these different settings are analyzed. This paper reflects on a possible role of RFA in resectable CRLM.

Circular ‘superelastic’ compression anastomosis: From the animal lab to clinical practice

The recent development of a compression device using shape memory Nitinol technogy to create an end‐to‐end anastomosis has renewed the interest in sutureless anastomotic techniques. A phase II, prospective open label clinical trial was started in May 2007 to evaluate the feasibility and safety of this new anastomotic device. Fourty patients who need left colectomy or high anterior resection for either diverticular disease or adenocarcinoma will be recruited in two academic hospitals (Uppsala,Sweden and Leuven, Belgium). Clinical leakage is the primary endpoint. Only preliminary results are available to date as the recruitment is ongoing. The median age of the first ten patients is 57.5 years (44–72). No anastomotic leakage occurred. The median hospital stay was 4.0 days. Only three patients noticed the passage of the ring through the anal canal. By three weeks no ring was sustained in the gastrointestinal tract as was objectified by plain X‐ray. First clinical use of this new anastomotic device seems promising. Final results for the total phase II trial are awaited. A prospective randomized trial to compare the efficacy of the EndoCar 28 with conventional stapling should be the next step.

Unresectable peritoneal carcinomatosis from colorectal cancer: a single center experience.

For unresectable peritoneal carcinomatosis (PC) median overall survival (OS) is 5–6 months. This article analyzes patients with PC from colorectal cancer (CRC) uneligible for debulking and hyperthermic intra‐peritoneal chemotherapy, describing patient‐ and tumor‐related factors possibly affecting survival.

Pazopanib, a Receptor Tyrosine Kinase Inhibitor, Suppresses Tumor Growth through Angiogenesis in Dedifferentiated Liposarcoma Xenograft Models

INTRODUCTION: The rarity of dedifferentiated liposarcoma (DDLPS) and the lack of experimental DDLPS models limit the development of novel therapeutic strategies. Pazopanib (PAZ) is a tyrosine kinase inhibitor that is approved for the treatment of non-adipocytic advanced soft tissue sarcoma. The activity of this agent has not yet been properly explored in preclinical liposarcoma models nor in a randomized phase Ш clinical trial in this entity. The aim of the present study was to investigate whether PAZ had antitumor activity in DDLPS models in vivo. MATERIAL AND METHODS: We established two patient-derived DDLPS xenograft models (UZLX-STS3 and UZLX-STS5) through implantation of tumor material from sarcoma patients in athymic nude NMRI mice. An animal model of the SW872 liposarcoma cell line was also used. To investigate the efficacy of PAZ in vivo, mice bearing tumors were treated for 2 weeks with sterile water, doxorubicin (1.2 mg/kg, intraperitoneally, twice per week), PAZ [40 mg/kg, orally (p.o.), twice per day], or PAZ plus doxorubicin (same schedules as for single treatments). RESULTS: Patient-derived xenografts retained the histologic and molecular features of DDLPS. PAZ significantly delayed tumor growth by decreasing proliferation and inhibited angiogenesis in all models tested. Combining the angiogenesis inhibitor with an anthracycline did not show superior efficacy. CONCLUSION: These results suggest that PAZ has potential antitumor activity in DDLPS primarily through antiangiogenic effects and therefore should be explored in clinical trials.

Hypoxia driven gene expression is an independent prognostic factor in stage II and III colon cancer patients

Purpose: Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients. Experimental Design: Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray datasets. These datasets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin-embedded material of 126 patients with colon cancer treated in our center. Results: In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected P ≤ 0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n = 224). With a fourth published dataset (n = 177), the six-gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease-free survival at three years (77.3%) compared with high CCHS patients (46.4%; log-rank, P = 0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs. 52.2%; P = 0.001). Conclusions: Hypoxia-driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A six-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledge on molecular classification of colon cancer. Clin Cancer Res; 20(8); 2159–68. ©2014 AACR.

Diffuse reflectance spectroscopy: toward real‐time quantification of steatosis in liver

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real‐time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy‐eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients. Liver steatosis was quantified from the collected optical spectra and compared with the histology analysis from the measurement location by three independent pathologists. Twenty two patients were diagnosed with <5% steatosis, 15 patients had mild steatosis, and four had moderate steatosis. Severe steatosis was not identified. Intraclass correlation between the pathologists analysis was 0.949. A correlation of 0.854 was found between the histology and DRS analyses of liver steatosis ex vivo. For the same liver tissue, a correlation of 0.925 was demonstrated between in vivo and ex vivo DRS analysis for steatosis quantification. DRS can quantify steatosis in liver tissue both in vivo and ex vivo with good agreement compared to histopathology analysis. This analysis can be performed real time and may therefore be useful for fast objective assessment of liver steatosis in liver surgery.

Nuclear inclusion bodies of mutant and wild‐type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodeling by p53 aggregation.

Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies, and identified nuclear inclusion bodies (nIBs) of transcriptionally inactive mutant or wild‐type p53 as the most frequent aggregation‐like phenotype across six different cancer types. p53‐positive nIBs co‐stained with nuclear aggregation markers, and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders. In cell culture, tumour‐associated stress was a strong inducer of p53 aggregation and nIB formation. This was most prominent for mutant p53, but could also be observed in wild‐type p53 cell lines, for which nIB formation correlated with the loss of p53s transcriptional activity. Importantly, protein aggregation also fuelled the dysregulation of the proteostasis network in the tumour cell by inducing a hyperactivated, oncogenic heat‐shock response, to which tumours are commonly addicted, and by overloading the proteasomal degradation system, an observation that was most pronounced for structurally destabilized mutant p53. Patients showing tumours with p53‐positive nIBs suffered from a poor clinical outcome, similar to those with loss of p53 expression, and tumour biopsies showed a differential proteostatic expression profile associated with p53‐positive nIBs. p53‐positive nIBs therefore highlight a malignant state of the tumour that results from the interplay between (1) the functional inactivation of p53 through mutation and/or aggregation, and (2) microenvironmental stress, a combination that catalyses proteostatic dysregulation. This study highlights several unexpected clinical, biological and therapeutically unexplored parallels between cancer and neurodegeneration. Copyright