Outcome of Colonic Surgery in Elderly Patients with Colon Cancer

Introduction. Colonic cancer is one of the most commonly diagnosed malignancies and most often occurs in patients aged 65 years or older. Aim. To evaluate the outcome of colonic surgery in the elderly in our hospital and to compare five-year survival rates between the younger and elderly patients. Methods. 207 consecutive patients underwent surgery for colon cancer. Patients were separated in patients younger than 75 and older than 75 years. Results. Elderly patients presented significantly more (P < .05) as a surgical emergency, had a longer duration of admission and were more often admitted to the ICU (P < .01). Also, elderly patients had significant more co-morbidities, especially cardiovascular pathology (P < .01). Post-operative complications were seen more often in the elderly, although no significant difference was seen in anastomotic leakage. The five-year survival rate in the younger group was 62% compared with 36% in the elderly (P < .05). DFS was 61% in the younger patients compared with 32% in the elderly (P < .05). Conclusion. Curative resection of colonic carcinoma in the elderly is well tolerated and age alone should not be an indication for less aggressive therapy. However, the type and number of co-morbidities influence post-operative mortality and morbidity

Limitations of the nested reverse transcriptase polymerase chain reaction on tyrosinase for the detection of malignant melanoma micrometastases in lymph nodes

The specificity and sensitivity of the nested reverse transcriptase polymerase chain reaction (RT-PCR) on tyrosinase was studied, for the detection of micrometastases of malignant melanoma. The specificity was assessed in the blood of six healthy donors, four patients with non-melanoma cancers of which one patient was treated with granulocyte-colony stimulating factor. Lymph nodes of nine patients without malignant melanoma were tested and four cell lines of various other tumours. Six of the nine non-melanoma lymph nodes were positive in this assay. The sensitivity was tested in a spike experiment in vitro, using a melanoma cell line. The detection limit was ten melanoma cells per 107peripheral blood lymphocytes. © 2000 Cancer Research Campaig

Spontaneous splenic rupture in infectious mononucleosis

Background: Two cases are presented: A 16-year-old female (patient A), presented at the emergency department with a continuously stabbing abdominal pain in the upper left abdomen. Since 1 month, she suffered from a sore throat, fatigue and weight loss. Physical examination revealed a sick girl with clear consciousness and no paleness. Her heart rate was 100 beats per minute (bpm) and blood pressure was 110/60 mmHg. Blood analysis showed a decreased hemoglobin level of 5.3 mmol/L

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial

Quimioteràpia; Càncer de pàncrees localment avançat; Ablació per radiofreqüènciaQuimioterapia; Cáncer de páncreas localmente avanzado; Ablación por radiofrecuenciaChemotherapy; Locally advanced pancreatic cancer; Radiofrequency ablationBackground Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. Methods The “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. Discussion The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment.Olympus Netherlands BV supported the investigator-initiated PELICAN trial with material support by providing the RFA generators and electrodes for the study. They did not have and will not have any influence on the trial design, data collection, interpretation of the data, manuscript development, or decision to publish. Furthermore, the study protocol has undergone full external peer review and received a data management and monitoring grant from the Dutch Cancer Society (grant number 2014-7244)

Microenvironment involved in FPR1 expression by human glioblastomas

Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.</p

Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model

PURPOSE: The reoperation rate for breast-conserving surgery is as high as 15-30% due to residual tumor in the surgical cavity after surgery. In vivo tumor-targeted optical molecular imaging may serve as a red-flag technique to improve intraoperative surgical margin assessment and to reduce reoperation rates. Cysteine cathepsins are overexpressed in most solid tumor types, including breast cancer. We developed a cathepsin-targeted, quenched fluorescent activity-based probe, VGT-309, and evaluated whether it could be used for tumor detection and image-guided surgery in syngeneic tumor-bearing mice. METHODS: Binding specificity of the developed probe was evaluated in vitro. Next, fluorescent imaging in BALB/c mice bearing a murine breast tumor was performed at different time points after VGT-309 administration. Biodistribution of VGT-309 after 24 h in tumor-bearing mice was compared to control mice. Image-guided surgery was performed at multiple time points tumors with different clinical fluorescent camera systems and followed by ex vivo analysis. RESULTS: The probe was specifically activated by cathepsins X, B/L, and S. Fluorescent imaging revealed an increased tumor-to-background contrast over time up to 15.1 24 h post probe injection. In addition, VGT-309 delineated tumor tissue during image-guided surgery with different optical fluorescent imaging camera systems. CONCLUSION: These results indicate that optical fluorescent molecular imaging using the cathepsin-targeted probe, VGT-309, may improve intraoperative tumor detection, which could translate to more complete tumor resection when coupled with commercially available surgical tools and techniques

Radiofrequente ablatiebehandeling van de oudere patiënte met een mammacarcinoom

Het mammacarcinoom is een belangrijk gezondheidsprobleem in de in omvang toenemende geriatrische populatie. De behandeling van deze fragiele groep patiënten is een uitdaging voor de behandelend arts. Enerzijds geeft onderbehandeling aanleiding tot een hogere incidentie van recidief tumoren alsook tumorgerelateerde mortaliteit. Anderzijds leidt overbehandeling tot iatrogene morbiditeit en mortaliteit. Minimaal invasieve behandelingstechnieken worden in toenemende mate in de literatuur beschreven en bieden nieuwe therapeutische mogelijkheden voor patiënten die niet voor conventionele chirurgie in aanmerking komen. Bij diverse minimaal invasieve tumor ablatie technieken wordt een maligne laesie onder controle van de beeldvormende technieken selectief behandeld met een minimale schade aan het omliggende weefsel en een goede lokale tumorcontrole. De procedure kan plaatsvinden onder lokale anesthesie. Radiofrequente ablatie lijkt een effectieve en veilige methode in de behandeling van oudere, inoperabele patiënten met kleinere (< 3 cm) mamma tumoren

High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

Background Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival. Methods From 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results Of 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49-0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45-0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47-0.88, P = 0.001). Conclusions HGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future

Disruption of the MDM2–p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway

Wild-type p53 has a major role in the response and execution of apoptosis after chemotherapy in many cancers. Although high levels of wild-type p53 and hardly any TP53 mutations are found in testicular cancer (TC), chemotherapy resistance is still observed in a significant subgroup of TC patients. In the present study, we demonstrate that p53 resides in a complex with MDM2 at higher cisplatin concentrations in cisplatin-resistant human TC cells compared with cisplatin-sensitive TC cells. Inhibition of the MDM2–p53 interaction using either Nutlin-3 or MDM2 RNA interference resulted in hyperactivation of the p53 pathway and a strong induction of apoptosis in cisplatin-sensitive and -resistant TC cells. Suppression of wild-type p53 induced resistance to Nutlin-3 in TC cells, demonstrating the key role of p53 for Nutlin-3 sensitivity. More specifically, our results indicate that p53-dependent induction of Fas membrane expression (∼threefold) and enhanced Fas/FasL interactions at the cell surface are important mechanisms of Nutlin-3-induced apoptosis in TC cells. Importantly, an analogous Fas-dependent mechanism of apoptosis upon Nutlin-3 treatment is executed in wild-type p53 expressing Hodgkin lymphoma and acute myeloid leukaemia cell lines. Finally, we demonstrate that Nutlin-3 strongly augmented cisplatin-induced apoptosis and cell kill via the Fas death receptor pathway. This effect is most pronounced in cisplatin-resistant TC cells