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Open access

Tomasz Michalik, Rafał Matkowski, Przemyslaw Biecek, Jozef Forgacz and Bartlomiej Szynglarewicz

Abstract

Background

Anterior resection with total mesorectal excision (TME) of ultralow rectal cancer may result in the increased risk of the anastomotic leakage (AL). The aim of this study was to evaluate the usefulness of the gentamicin-collagen sponge (GCS) for the protection against symptomatic AL and investigate association between AL and local relapse (LR).

Patients and methods

A series of 158 patients with ultralow rectal cancer was studied. All the patients underwent R0 sphincter-saving TME with anastomosis wrapping using GCS. In none of the cases a temporary protective stoma was constructed.

Results

AL rate was 3.2% (5/158) while median time to AL diagnosis was 5 days following surgery (range 3-15). There was no postoperative and leakage-related mortality. Patient age > 75 years and smoking were independent risk factors related to significantly increased AL rate: 12.5% vs. 0.8% (P = 0.0004) and 5.7% vs. 0% P = 0.043), respectively. LR was observed in 12% of cases. It was highly significantly more common and developed earlier in patients who have had AL when compared with non-AL group: 80% vs. 9% (P = 0.00001) and 8.5 vs. 17 months (P = 0.014), respectively.

Conclusions

Anastomosis wrapping with GCS after anterior resection with TME is a safe procedure resulting in the low incidence of anastomotic leakage which may be also associated with decreased risk of local relapse.

Open access

Niklas Verloh, Isabel Jensch, Lukas Lürken, Michael Haimerl, Marco Dollinger, Philipp Renner, Philipp Wiggermann, Jens Martin Werner, Florian Zeman, Christian Stroszczynski and Lukas Philipp Beyer

Abstract

Background

To compare the frequency of adverse events of thermal microwave (MWA) and radiofrequency ablation (RFA) with non-thermal irreversible electroporation (IRE) in percutaneous ablation of hepatocellular carcinoma (HCC).

Patients and methods

We retrospectively analyzed 117 MWA/RFA and 47 IRE procedures (one tumor treated per procedure; 144 men and 20 women; median age, 66 years) regarding adverse events, duration of hospital and intensive care unit (ICU) stays and occurrence of a post-ablation syndrome. Complications were classified according to the Clavien & Dindo classification system.

Results

70.1% of the RFA/MWA and 63.8% of the IRE procedures were performed without complications. Grade I and II complications (any deviation from the normal postinterventional course, e.g., analgesics) occurred in 26.5% (31/117) of MWA/RFA and 34.0% (16/47) of IRE procedures. Grade III and IV (major) complications occurred in 2.6% (3/117) of MWA/RFA and 2.1% (1/47) of IRE procedures. There was no significant difference in the frequency of complications (p = 0.864), duration of hospital and ICU stay and the occurrence of a post-ablation syndrome between the two groups.

Conclusions

Our results suggest that thermal (MWA and RFA) and non-thermal IRE ablation of malignant liver tumors have comparable complication rates despite the higher number of punctures and the lack of track cauterization in IRE.

Open access

Manca Garbajs, Primoz Strojan and Katarina Surlan-Popovic

Abstract

Background

In the study, the value of pre-treatment dynamic contrast-enhanced (DCE) and diffusion weighted (DW) MRI-derived parameters as well as their changes early during treatment was evaluated for predicting disease-free survival (DFS) and overall survival (OS) in patients with locoregionally advanced head and neck squamous carcinoma (HNSCC) treated with concomitant chemoradiotherapy (cCRT) with cisplatin.

Patients and methods

MRI scans were performed in 20 patients with locoregionally advanced HNSCC at baseline and after 10 Grays (Gy) of cCRT. Tumour apparent diffusion coefficient (ADC) and DCE parameters (volume transfer constant [Ktrans], extracellular extravascular volume fraction [ve], and plasma volume fraction [Vp]) were measured. Relative changes in parameters from baseline to 10 Gy were calculated. Univariate and multivariate Cox regression analysis were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify parameters with the best diagnostic performance.

Results

None of the parameters was identified to predict for DFS. On univariate analysis of OS, lower pre-treatment ADC (p = 0.012), higher pre-treatment Ktrans (p = 0.026), and higher reduction in Ktrans (p = 0.014) from baseline to 10 Gy were identified as significant predictors. Multivariate analysis identified only higher pre-treatment Ktrans (p = 0.026; 95% CI: 0.000–0.132) as an independent predictor of OS. At ROC curve analysis, pre-treatment Ktrans yielded an excellent diagnostic accuracy (area under curve [AUC] = 0.95, sensitivity 93.3%; specificity 80 %).

Conclusions

In our group of HNSCC patients treated with cisplatin-based cCRT, pre-treatment Ktrans was found to be a good predictor of OS.

Open access

Mohamed A.F. Mourad and Mahmoud M. Higazi

Abstract

Background

This study aimed to evaluate the efficacy of three MR imaging parameters, which are tumour thickness, para-lingual distance and apparent diffusion coefficient (ADC) value for prediction of cervical lymph nodes metastasis in cancer tongue patients.

Patients and methods

Fifty patients with proved cancer tongue by histopathological examination underwent MRI examination. T1 and T2- weighted MRI, diffusion-weighted images and post-contrast T1 fat suppression sequences were used.

Results

The patients were classified according to lymph nodes involvement as seen by MRI into two groups. Significant differences between positive and negative nodes groups were observed regarding tumour thickness and para-lingual distance (p-values = 0.008 and 0.003 respectively). ROC curve analyses revealed cut-off values >13.8 mm and ≤ 3.3 mm for tumour thickness and para-lingual distance respectively for prediction of nodes involvement. No significant differences between patients with and without cervical lymph nodes metastasis were found regarding corresponding ADC value of the tumour (p-value = 0.518).

Conclusions

Para-lingual distance and tumour thickness are factors that could influence pre-operative judgment and prognosis of tongue cancer patients. ADC value of the tumour itself seem not to be a reliable index of cancer progression to regional lymph nodes.

Open access

Martina Rebersek, Tanja Mesti, Marko Boc and Janja Ocvirk

Abstract

Background

Histological parameters of primary tumour and nodal metastases are prognostic factors for survival of operable colorectal (CRC) patients, but not predictive for response rate of systemic therapy. KRAS mutations in codons 12 and 13 were first recognized as a predictive factor for resistance to anti-EGFR monoclonal antibodies. Not all patients with wild-type KRAS (wtKRAS) respond to anti-EGFR antibody treatment. Additional mechanisms of resistance may activate mutations of the other main EGFR effectors pathway, such as other mutations in RAS gene, mutations in P13K and PTEN expression.

Patients and methods

In the prospective study prognostic and predictive impact of histological parameters of primary tumour, KRAS and BRAF mutations on overall survival (OS) and objective response (OR) rate of metastatic CRC (mCRC) patients treated with 1st line systemic therapy were analysed. We additionally retrospectively analysed other mutations in RAS genes and their impact on survival and time to progression.

Results

From November 2010 to December 2012, we enrolled 154 patients in the study, 95 men and 59 women. Mutations in KRAS gene and V600E BRAF gene were found in 42% and in 3% of patients, respectively. Median OS of the patients with T1, T2 and T3 tumour was 65.4 months (95% CI, 55.7–75.6) while in patients with T4 tumour, lymphangiosis, vascular and perineural invasion it has not been reached yet. Median OS of the patients with G1, G2 and G3 of tumour differentiation was 65.6 (95% CI, 53.7–77.5) and 25.3 months (95% CI, 16.6–34.1), respectively. Median OS of the patients with stage N0, N1 and N2 was 65.6 (95% CI, 56.4–74.8) and 58.0 months (95% CI, 21.9–94.2), respectively. Median OS of wtKRAS and mutated KRAS patients was 56.5 (95% CI, 48.2–64.9) and 58 months (95% CI, 52.6–63.4), respectively. Median OS of mutated codon 12 and codon 13 patients was 57 (95% CI, 50.9–64.4) and 44 months (95% CI, 40.1–48.4), respectively. Median OS of wtBRAF and of mutated BRAF patients was 59.2 (95% CI, 52.5–65.9) and 27.6 months (95% CI, 12.6–42.5), respectively. wtKRAS significantly affected the response to the first systemic therapy (p = 0.028), while other parameters did not affected it, p= 0.07. In 14 patients (17%), additional mutations in NRAS gene, codon 61 and codon 146 were found. Median OS of wtNRAS, codon 61 and 146 patients was 67.1 months (50.3–67.6) while median OS of mutated NRAS patients has not been reached yet (p = 0.072). Median time to progression of wtNRAS, codon 61 and 146 patients was 11.7 months (10.4–14.5) while median time to progression of mutated NRAS patients was 7.9 months (6.1–11.0), (p = 0.025).

Conclusions

Mutated BRAF, N2 and G3 of primary tumour were poor prognostic factors for OS in mCRC patients. wtKRAS significantly affected the response to the first line systemic therapy. Histological parameters included in the analysis and mutated BRAF did not affect significantly the efficacy of 1st line systemic therapy in mCRC patients.

Open access

Mateja Prunk, Milica Perisic Nanut, Jerica Sabotic, Urban Svajger and Janko Kos

Abstract

Background

Cystatin F is a protein inhibitor of cysteine peptidases, expressed predominantly in immune cells and localised in endosomal/lysosomal compartments. In cytotoxic immune cells cystatin F inhibits both the major pro-granzyme convertases, cathepsins C and H that activate granzymes, and cathepsin L, that acts as perforin activator. Since perforin and granzymes are crucial molecules for target cell killing by cytotoxic lymphocytes, defects in the activation of either granzymes or perforin can affect their cytotoxic potential.

Materials and methods

Levels of cystatin F were assessed by western blot and interactions of cystatin F with cathepsins C, H and L were analysed by immunoprecipitation and confocal microscopy. In TALL-104 cells specific activities of the cathepsins and granzyme B were determined using peptide substrates.

Results

Two models of reduced T cell cytotoxicity of TALL-104 cell line were established, either by treatment by ionomycin or by immunosuppressive transforming growth factor beta. Reduced cytotoxicity correlated with increased levels of cystatin F and with attenuated activities of cathepsins C, H and L and of granzyme B. Co-localisation of cystatin F and cathepsins C, H and L and interactions between cystatin F and cathepsins C and H were demonstrated.

Conclusions

Cystatin F is designated as a possible regulator of T cell cytotoxicity, similar to its role in natural killer cells.

Open access

Barbara Senk, Katja Goricar, Viljem Kovac, Vita Dolzan and Alenka Franko

Abstract

Background

Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment.

Patients and methods

The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis.

Results

AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37–0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27–0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27–0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00–4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01–9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00–8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00–13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13–19.05, P = 0.034) in additive model.

Conclusions

AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.

Open access

Li Ma, Yu Men, Lingling Feng, Jingjing Kang, Xin Sun, Meng Yuan, Wei Jiang and Zhouguang Hui

Abstract

Background

The mainstay therapy for locally advanced non-small cell lung cancer is concurrent chemoradiotherapy. Loco-regional recurrence constitutes the predominant failure patterns. Previous studies confirmed the relationship between increased biological equivalent doses and improved overall survival. However, the large randomized phase III study, RTOG 0617, failed to demonstrate the benefit of dose-escalation to 74 Gy compared with 60 Gy by simply increasing fraction numbers.

Conclusions

Though effective dose-escalation methods have been explored, including altered fractionation, adapting individualized increments for different patients, and adopting new technologies and new equipment such as new radiation therapy, no consensus has been achieved yet.

Open access

Katarina Cerne, Benjamin Hadzialjevic, Erik Skof, Ivan Verdenik and Borut Kobal

Abstract

Background

Osteopontin (sOPN) is a promising blood tumour marker for detecting epithelial ovarian cancer (EOC). However, other clinical uses of sOPN as a tumour marker in EOC are still lacking. Since sOPN concentrations in serum are not associated with those in ascites, we compared clinical value of sOPN concentrations in the two body fluids.

Patients and methods

The study included 31 women with advanced EOC and 34 women with benign gynaecological pathology. In the EOC group, serum for sOPN analysis was obtained preoperatively, after primary debulking surgery and after chemotherapy. In the control group, serum was obtained before and after surgery. Ascites and peritoneal fluid were obtained during surgery. sOPN concentrations were determined by flow cytometry bead-based assay.

Results

The sensitivity and specificity of sOPN in detecting EOC was 91.2% and 90.3% (cut-off = 47.4 ng/ml) in serum, and 96.8% and 100% (cut-off = 529.5 ng/ml) in ascites. Kaplan-Meier analysis showed a significant association between higher serum sOPN concentration and overall survival (p = 0.018) or progression free survival (p = 0.008). Higher ascites sOPN concentrations were associated with suboptimally debulked tumour and unresectable disease. Higher serum sOPN concentrations were associated with refractory disease or incomplete response to platinum-based chemotherapy.

Conclusions

The study showed that ascites sOPN level mirrors present disease and is superior to serum level for diagnostic purposes and surgical planning, although the end result of treatment is the response of the whole body in fighting the disease. The preoperative sOPN concentration in serum thus better reflects disease outcome.

Open access

Janez Simenc, Damijana Mojca Juric and Metoda Lipnik-Stangelj

Abstract

Background

Astrocytes maintain central nerve system homeostasis and are relatively resistant to cell death. Dysfunction of cell death mechanisms may underlie glioblastoma genesis and resistance to cancer therapy; therefore more detailed understanding of astrocytic death modalities is needed in order to design effective therapy. The purpose of this study was to determine the effect of VAS2870, a pan-NADPH oxidase inhibitor, on staurosporine-induced cell death in astrocytes.

Materials and methods

Cultured rat astrocytes were treated with staurosporine as activator of cell death. Cell viability, production of reactive oxygen species (ROS), and mitochondrial potential were examined using flow cytometric analysis, while chemiluminescence analysis was performed to assess caspase 3/7 activity and cellular ATP.

Results

We show here for the first time, that VAS2870 is able to prevent staurosporine-induced cell death. Staurosporine exerts its toxic effect through increased generation of ROS, while VAS2870 reduces the level of ROS. Further, VAS2870 partially restores mitochondrial inner membrane potential and level of ATP in staurosporine treated cells.

Conclusions

Staurosporine induces cell death in cultured rat astrocytes through oxidative stress. Generation of ROS, mitochondrial membrane potential and energy level are sensitive to VAS2870, which suggests NADPH oxidases as an important effector of cell death. Consequently, NADPH oxidases activation pathway could be an important target to modulate astrocytic death.