BACKGROUND: Advanced pancreatic adenocarcinoma still remains associated with a desperate prognosis. Nevertheless, treatment options for patients with metastasized disease have improved considerably over the last few year...BACKGROUND: Advanced pancreatic adenocarcinoma still remains associated with a desperate prognosis. Nevertheless, treatment options for patients with metastasized disease have improved considerably over the last few years. Recently, cytotoxic combination therapies such as the FOLFIRINOX regimen and combined nab-paclitaxel/gemcitabine have shown improved overall survival compared to gemcitabine alone. There is still no standard of care in second-line therapy for patients with disease progression. CASE REPORT: We report the case of a 47-year-old patient who dramatically responded to second-line treatment with nab-paclitaxel and gemcitabine after primary progression to the FOLFIRINOX protocol. CONCLUSION: Second-line treatment after FOLFIRINOX is feasible for patients with good performance status. Our case report supports preclinical findings that suggest that pancreatic cancer is a heterogeneous disease. Further studies that characterize possible subgroups and identify predictive molecular markers to guide therapy are warranted.
BACKGROUND: Treatment of germ cell tumours with cisplatin-based chemotherapy results in cure for the majority of patients. There is, however, a small but significant mortality rate, reported to be higher in patients with...BACKGROUND: Treatment of germ cell tumours with cisplatin-based chemotherapy results in cure for the majority of patients. There is, however, a small but significant mortality rate, reported to be higher in patients with multiple co-morbidities. CASE REPORT: We report our management of a renal transplant patient with spina bifida, who was diagnosed with stage IIIC, poor-risk, non-seminomatous germ cell carcinoma. A marker-negative partial response, which has been maintained more than 2 years following completion of treatment, was seen following chemotherapy with cisplatin and etoposide. Performance status has been preserved at pre-treatment levels. CONCLUSION: Administration of cisplatin-based chemotherapy is feasible for treatment of renal transplant patients with advanced non-seminomatous germ cell tumours. Treatment strategies require careful planning and monitoring. Dose modifications may be required. This case highlights a favourable outcome in spite of multiple obstacles to ideal management.
BACKGROUND: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal cancer and crucial to tumorigenesis. Herein, we identified the role of miR-145 in esophageal squamous cell...BACKGROUND: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal cancer and crucial to tumorigenesis. Herein, we identified the role of miR-145 in esophageal squamous cell carcinoma (ESCC) development in vitro and in vivo. MATERIAL AND METHODS: miR-145 expression was investigated in 40 ESCC samples as well as 5 ESCC cell lines by real-time polymerase chain reaction. Crystal violet and transwell assays were conducted to explore the effects of miR-145 on the proliferation and invasion of human ESCC cell lines, respectively. The impact of overexpression of miR-145 on putative target c-Myc was subsequently confirmed via Western blot. RESULTS: miR-145 expression was frequently downregulated in ESCC specimens and cell lines compared with adjacent normal tissues (p < 0.05). Overexpression of miR-145 suppressed (p < 0.05) ESCC cell proliferation and invasion, as well as the growth of xenograft tumors in mice. Overexpression of miR-145 significantly decreased (p < 0.05) the protein level of c-Myc which has previously been identified as a direct target of miR-145. CONCLUSION: Our results demonstrate that overexpression of miR-145 inhibits tumor growth in part by targeting c-Myc. Our findings revealed that miR-145 may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC.
BACKGROUND: Knowing the status of the internal mammary lymph (IML) nodes is important for accurate staging and appropriate selection of subsequent treatment in breast cancer. We conducted a meta-analysis to clarify the r...BACKGROUND: Knowing the status of the internal mammary lymph (IML) nodes is important for accurate staging and appropriate selection of subsequent treatment in breast cancer. We conducted a meta-analysis to clarify the rate of IML node metastasis in breast cancer patients and discussed the importance of this finding. METHODS: We retrieved articles from the literature that reported positive rates of IML node metastasis in breast cancer patients. The quality of the selected articles was assessed using the 'Methodological Index for Non-Randomized Studies'. The heterogeneity was tested, and publication bias was assessed using a funnel plot. Finally, the positive rate of IML node metastasis in breast cancer patients was calculated using the random-effects model. RESULTS: 15 articles met the inclusion criteria and a total of 4,248 patients were included in the analysis. Heterogeneity across the studies was statistically significant (p = 0.014); thus, the random-effects model was used and the calculated positive rate of IML node metastasis was 23% (95% confidence interval (CI), 0.21-0.25). CONCLUSIONS: Approximately 23% of the breast cancer patients had IML node metastases, for which the prognosis is generally poor. Accurate staging and integrated treatment are necessary to improve the survival of these patients.
BACKGROUND: Delayed diagnosis of squamous cell carcinoma (SCC) increases recurrence, metastatic potential, and management costs. This study aims to identify risk factors of patient-related delayed presentation in cutaneo...BACKGROUND: Delayed diagnosis of squamous cell carcinoma (SCC) increases recurrence, metastatic potential, and management costs. This study aims to identify risk factors of patient-related delayed presentation in cutaneous SCC. PATIENTS AND METHODS: A total of 513 patients, who first sought care for cutaneous lesions that were subsequently removed and histologically confirmed as SCCs, were included. Attitude to symptoms, psychosocial profile, and reasons for delayed presentation were obtained via a structured questionnaire-based interview. First presentation > 3 months from the onset of symptoms was considered as delayed. RESULTS: Mean presentation time was 3.90 ± 2.05 months, while 186 patients delayed presentation. Multivariate logistic regression analysis revealed that serious co-morbidity (p = 0.003), low education level (p < 0.001), non-recognition of the seriousness of symptoms (p < 0.001), a 'wait and see' attitude (p < 0.001), and fatalism (p = 0.005) were independent determinants of significantly higher risk for delayed presentation. In contrast, female sex (p = 0.006), new lesion (p = 0.012), accessible topography (p = 0.019), size increase (p = 0.002), color change (p = 0.017), non-healing wound (p = 0.048), and presence of social support/advice (p < 0.001) were independent determinants significantly associated with early presentation. CONCLUSION: Recognition of symptom seriousness and elimination of factors hindering self-referral may increase awareness and promote early patient presentation and diagnosis of cutaneous SCC.
BACKGROUND: We have analyzed the patient population of one clinic (Charité) over a period of 15 years. Besides the changes in the technical facilities and therapeutical guidelines during these years, this period also ref...BACKGROUND: We have analyzed the patient population of one clinic (Charité) over a period of 15 years. Besides the changes in the technical facilities and therapeutical guidelines during these years, this period also reflects the changes in the health system attributable to the reunification of East and West Germany. Until now only few analyses for breast cancer patients from the German speaking area have been reported. PATIENTS AND METHODS: All 2,062 patients undergoing surgical treatment for breast cancer between 1984 and 1998 were documented and followed up until 2007. The analysis included 1,560 patients with a primary breast cancer who fulfilled certain inclusion criteria. The treatment strategies applied to this population are presented in 3 time periods (1984-1990, 1991-1993, and 1994-1998). The effects of prognostic factors on overall survival were investigated using univariate analyses. RESULTS: The percentage of pT1 tumors changed from 50.7% in the first period to 63.1% in the third period. The percentage of node-negative patients hardly changed with time (on average 61.6%). However, the percentage of patients with less than 10 assessed nodes decreased from 48.4% to 6.7% and 2.5% for the 3 periods, respectively. Therapeutic strategies changed drastically. Survival rate increased substantially, most likely due to improved therapeutic strategies, but also for other reasons not considered in the analysis.
BACKGROUND: Colorectal cancer (CRC) plays an important role in cancer mortality and morbidity. This study examined colorectal tissues for RAS, BRAF, and TP53 gene mutations to assess their value as indicators of outcomes...BACKGROUND: Colorectal cancer (CRC) plays an important role in cancer mortality and morbidity. This study examined colorectal tissues for RAS, BRAF, and TP53 gene mutations to assess their value as indicators of outcomes of CRC therapy. MATERIAL AND METHODS: DNA was extracted from tissues taken from 165 patients with CRC. RAS gene mutations (exons 2 and 3) were detected by primer extension analysis. BRAF gene mutations (V600E) were detected by high resolution melting (HRM) analysis. TP53 gene mutations (exons 5-8) were detected by direct sequencing. RESULTS: RAS, BRAF, and TP53 mutations occurred in 36.97% (61/165), 4.24% (7/165), and 37.58% (62/165), respectively. The KRAS mutation is a predictor for poor 5-year survival (p = 0.05), and the co-presence of KRAS and TP53 mutations correlates with lymph node involvement (p = 0.029), tumor stage (p = 0.029), and poor survival (p = 0.021). Multivariate analysis adjusted for tumor size, histologic grade, lymph node metastasis, sex, and age also indicated that KRAS mutations correlate significantly with overall survival (p = 0.036). CONCLUSION: The KRAS mutation is not present in about one-third of CRC patients, and therefore other gene mutations need to be investigated to better understand the molecular mechanisms of CRC and its treatment.
BACKGROUND: The aim of this study was to examine the cardiac effects of anthracycline therapy based on speckle-tracking echocardiography (STE) and to identify patients at risk for cardiotoxicity. PATIENTS AND METHODS: Th...BACKGROUND: The aim of this study was to examine the cardiac effects of anthracycline therapy based on speckle-tracking echocardiography (STE) and to identify patients at risk for cardiotoxicity. PATIENTS AND METHODS: The study included 35 breast cancer (BC) and 15 lymphoma patients who were treated with anthracycline-based chemotherapy. Conventional echocardiography and STE were performed 1 month prior to and 1 month after chemotherapy. Longitudinal strain analysis was performed via STE using automated functional imaging. RESULTS: The ejection fraction (EF) and the fractional shortening values were significantly lower in the lymphoma group. There was a positive correlation between anthracycline dose and subclinical heart failure (p = 0.024). There was an increase in the myocardial performance index in both groups. After therapy, STE showed regional decreases in the longitudinal strain values in the BC group, but the global strain values did not differ. In the lymphoma group, the apical long-axis, the 4-chamber, and the global longitudinal strain values were significantly lower after therapy (p = 0.002, 0.041, and 0.004, respectively). The long-axis and global longitudinal strain values were significantly lower in the lymphoma patients with normal EF values (p = 0.01 and 0.05, respectively). CONCLUSION: Cardiotoxicity during the early phase of anthracycline treatment can be detected via STE prior to the observation of systolic function deterioration.
The aim of this systematic review was to examine the relationship between pre-operative peritumoral edema and survival in patients with glioblastoma multiforme (GBM). We searched for studies involving patients with GBM w...The aim of this systematic review was to examine the relationship between pre-operative peritumoral edema and survival in patients with glioblastoma multiforme (GBM). We searched for studies involving patients with GBM who underwent pre-operative imaging (magnetic resonance imaging and/or computed tomography) in which the peritumoral edema was assessed as a prognostic factor for survival. 7 retrospective studies met the eligibility criteria and were included in the study. 2 studies found that pre-operative peritumoral edema was an independent prognostic factor for decreased survival. 1 study found that survival was dependent on the severity of the peritumoral edema (minimal and severe: increased survival; moderate: decreased survival). 2 studies found that pre-operative peritumoral edema was a predictor of decreased survival based on univariate but not multivariate analysis. 1 study found that there was no relationship between pre-operative peritumoral edema and survival, while the remaining study found that patients with peritumoral edema had decreased survival compared with patients without peritumoral edema. There was considerable heterogeneity between the studies regarding the patient characteristics. The results of our systematic review are inconclusive; the available evidence does not definitely support or rule out an association between pre-operative peritumoral edema and survival. Hence, further, well-designed, prospective studies are clearly needed.
BACKGROUND: Pazopanib is a multi-targeted tyrosine kinase inhibitor that has recently been approved for treatment of advanced clear cell renal cell carcinoma (RCC). There are no previous reports of pazopanib triggering r...BACKGROUND: Pazopanib is a multi-targeted tyrosine kinase inhibitor that has recently been approved for treatment of advanced clear cell renal cell carcinoma (RCC). There are no previous reports of pazopanib triggering radiation recall dermatitis (RRD). CASE REPORT: A 60-year-old male patient was commenced on pazopanib for metastatic RCC 2 weeks prior to receiving radiotherapy (10×30 Gy) to bone metastases at the T9 and L4 vertebrae and right mid-shaft of humerus. Although there were no immediate complications from radiotherapy, 2 weeks after finishing radiation he developed a pruritic, erythematous, maculo-papular rash localized to the T9 and right humeral radiotherapy fields. The patient was diagnosed with RRD induced by pazopanib and commenced on a course of oral prednisolone, which resulted in resolution of his rash. He has now completed 5 months of pazopanib with no recurrence of RRD. CONCLUSION: We report the first case of RRD triggered by pazopanib. With increasing use of pazopanib for advanced RCC, clinicians must be aware of the possibility that RRD can occur in patients treated with this agent following radiotherapy.
BACKGROUND: Treatment of osteosarcoma of the extremities consists of surgical resection preceded and followed by chemotherapy, including high-dose methotrexate or adriamycin-based protocols. When distant relapse occurs,...BACKGROUND: Treatment of osteosarcoma of the extremities consists of surgical resection preceded and followed by chemotherapy, including high-dose methotrexate or adriamycin-based protocols. When distant relapse occurs, therapeutic options are scarce. Trabectedin, a DNA-binding agent, is indicated for the treatment of patients with advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide. In this indication, the 6-month progression-free survival is about 35-40%. Recent reports showed that some specific single nucleotide polymorphisms (SNPs) from DNA repair genes could be associated with sensitivity to trabectedin in soft tissue sarcomas. CASE REPORTS: We report our experience of 2 metastatic, heavily pre-treated osteosarcoma patients who were treated with trabectedin. Pyrosequencing analyses of tumors from both patients for several SNPs of the ERCC1, ERCC5 and BRAC1 genes were performed. Both patients showed major response to trabectedin, which was interestingly related with homozygoty of the common guanine allele of ERCC5 (G/G genotype; Asp/Asp) after pyrosenquencing analysis of tumors from both patients. This polymorphism was previously shown to be associated with better outcome in soft tissue sarcoma patients treated with trabectedin. CONCLUSION: Homozygoty for the wild-type Asp1104 SNP of the ERCC5 gene was found in 2 cases of relapsed osteosarcoma, who responded to trabectedin.
BACKGROUND: Germ cell tumor (GCT) patients are at risk of venous thromboembolic events (VTEEs). A higher incidence of VTEEs has been reported in GCT patients undergoing cisplatin-based chemotherapy. PATIENTS AND METHODS:...BACKGROUND: Germ cell tumor (GCT) patients are at risk of venous thromboembolic events (VTEEs). A higher incidence of VTEEs has been reported in GCT patients undergoing cisplatin-based chemotherapy. PATIENTS AND METHODS: A retrospective analysis of the incidence of and risk factors for VTEEs in 193 GCT patients receiving platinum-based chemotherapy in Hamburg, Germany, between 2000 and 2009 was performed. RESULTS: VTEEs occurred in 22 patients (11%). In only 4 patients, the VTEEs occurred during cisplatin-based chemotherapy, while 18 patients (81%) experienced VTEEs prior to initiation of chemotherapy. Pure seminoma, 'intermediate risk' (International Germ Cell Cancer Collaborative Group (IGCCCG)), retroperitoneal or supraclavicular lymph node metastases, elevated lactate dehydrogenase (LDH) levels, a central venous catheter (CVC), arterial hypertension, application of granulocyte colony-stimulating factor (G-CSF) and of ≥ 3 cycles of cisplatin-based chemotherapy could be identified as risk factors. 2 risk groups could be described: (i) VTEEs manifesting before chemotherapy in patients with seminoma, retroperitoneal tumor masses, and elevated LDH levels, and (ii) VTEEs occurring during chemotherapy applied via CVC in patients with supraclavicular lymph node metastases. CONCLUSIONS: The incidence of VTEEs in GCT patients was 11%, but in the majority of patients, the VTEEs occurred before the initiation of platinum-based chemotherapy. Supraclavicular lymph node metastases and use of a CVC are risk factors for VTEEs during chemotherapy.
BACKGROUND: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and ir...BACKGROUND: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors. METHODS: The patients received cisplatin 30 mg/m² and irinotecan 50 mg/m² weekly from week 1 to week 4, with SU5416 at either 65 mg/m² (dose level (DL)1) or 85 mg/m² (DL2) twice weekly for 6 weeks (1 cycle). Serial ¹⁸fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) and ¹⁵O-H₂O-PET scans were obtained. RESULTS: 13 patients were treated (7 on DL1, 6 on DL2); 7 patients completed at least 1 cycle of treatment. 3 patients experienced dose-limiting toxicity (DLT) at DL2 (grade 3 neutropenia and grade 3 thrombocytopenia causing treatment delay, grade 3 nausea/vomiting). No objective responses were observed at DL1, which was determined to be the maximum tolerated dose (MTD). 1 partial response (PR) was observed at DL2. ¹⁸FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST). CONCLUSIONS: SU5416 at 65 mg/m² twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. ¹⁸FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.
BACKGROUND: The aim of this study was to investigate the role of far upstream element-binding protein 1 (FUBP1) in gastric cancer development. PATIENTS AND METHODS: Using immunohistochemistry, we detected FUBP1 expressio...BACKGROUND: The aim of this study was to investigate the role of far upstream element-binding protein 1 (FUBP1) in gastric cancer development. PATIENTS AND METHODS: Using immunohistochemistry, we detected FUBP1 expression in 18 chronic superficial gastritis patients, 33 chronic atrophic gastritis patients, 21 moderate and severe gastric dysplasia patients, and 31 gastric cancer patients. FUBP1 mRNA expression in gastric cancer tissue and paraneoplastic tissue was measured with fluorescent quantitative reverse transcription polymerase chain reaction. RESULTS: The FUBP1 expression rates in the chronic atrophic gastritis, moderate and severe dysplasia, and gastric cancer patients were 51.51% (17/33), 76.19% (16/21), and 90.32% (28/31), respectively; these were higher than the expression rate of the chronic superficial gastritis patients (11.11%, 2/18). FUBP1 expression in the gastric cancer patients was significantly higher than that in the chronic atrophic gastritis patients. The relative amount (0.2593 ± 0.1209) of FUBP1 mRNA in the gastric cancer tissue was higher than that in paraneoplastic tissue (0.1969 ± 0.0211) (p < 0.05). There was a statistically significant correlation between overall survival rates and age, sex, lymph node metastasis, and distant metastasis (p < 0.05). CONCLUSION: FUBP1 expression differs among gastric tissues. There is a correlation between overall survival rates and age, sex, lymph node metastasis, and distant metastasis.
BACKGROUND: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors. METHODS: In a retrospe...BACKGROUND: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors. METHODS: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated. RESULTS: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%. The median overall survival (OS) was 59 days. 53% of the patients died at the palliative care unit. In the Cox proportional hazards model, 8 parameters indicated an unfavourable outcome: anorexia/nausea, disordered mental status, elevated lactate dehydrogenase, γ-glutamyltransferase, leukocyte count, hypoalbuminaemia, anaemia and hypercalcaemia. Based on these parameters 3 risk groups were defined: low risk (0-2 factors), intermediate risk (3-5 factors), and high risk (6-8 factors). Median survival for high-risk group was 13 days, for intermediate group 61 days, and for low-risk patients 554 days (p < 0.0001). CONCLUSION: Weakness/fatigue, pain and anorexia were the main symptoms leading to the hospitalisation of patients with gynaecological malignancies. Symptom and pain control was accomplished in 80% of cases. 8 parameters were identified as indicating a poor outcome, and patients showing at least 6 or more of these factors had a very limited prognosis. Although studied retrospectively, these results may be helpful for individual treatment decisions in patients with advanced gynaecological malignancies. Prospective data and the introduction of documentation systems could help to gain more powerful knowledge about the quality of palliative care.
BACKGROUND: The ratio of metastatic to dissected lymph nodes (lymph node ratio; LNR) is a sensitive and superior prognostic factor for lymph node evaluation, but its relationship to cancer subtypes is unclear. PATIENTS A...BACKGROUND: The ratio of metastatic to dissected lymph nodes (lymph node ratio; LNR) is a sensitive and superior prognostic factor for lymph node evaluation, but its relationship to cancer subtypes is unclear. PATIENTS AND METHODS: Data from 469 patients with axillary lymph node metastasis out of 640 early breast cancer cases were retrospectively analyzed. They were classified into 4 molecular subtypes; luminal A, luminal B HER2(+), HER2 overexpression, basal-like. LNRs were compared between groups and with other prognostic factors. RESULTS: The distribution of LNRs was 35.2% in luminal A, 43.2% in luminal B HER2(+), 46.9% in HER2 over-expression, and 39.1% in basal-like. A significant difference was found between luminal A and HER2 over-expression subtypes (p = 0.023). LNR was significantly correlated with tumor size and lymphovascular invasion, but not with other prognostic factors including menopausal status, laterality, grade, and perineural invasion. An LNR of 29.8% was defined as the cut-off value, and significant differences in survival rates were identified accordingly between basal-like and both luminal A (p = 0.003) and luminal B HER2(+) (p = 0.04). CONCLUSION: The LNR differs between some molecular subtypes of breast cancer, and it correlates with certain prognostic factors and survival. These data support using the LNR to assess breast cancer patients.
AIM: The aim of this study was to investigate the expression and clinical prognostic significance of adhesion molecules in nasopharyngeal carcinoma (NPC) tissues and peripheral blood. MATERIALS AND METHODS: Flow cytometr...AIM: The aim of this study was to investigate the expression and clinical prognostic significance of adhesion molecules in nasopharyngeal carcinoma (NPC) tissues and peripheral blood. MATERIALS AND METHODS: Flow cytometry assays for the expression levels of CD44v6 and CD62P protein in peripheral blood and tissues from controls and NPC patients were performed. Clinical and pathological features were reported and analyzed, and a survival study was carried out. RESULTS: The expression of CD44v6 and CD62P in NPC tissues and peripheral blood was higher than that of the control group (p < 0.05). Expression levels in peripheral blood of stage III/IV NPC patients was markedly higher than that of patients in stage I/II (p < 0.05), while it had no statistically significant difference in tissues (p > 0.05). The expression levels of CD44v6 and CD62P in the lymph gland metastasis and distant metastasis group were higher than groups without such metastasis (p < 0.05), and there was no statistical difference in NPC tissues (p > 0.05). The survival rates of NPC groups with low expression in the peripheral blood were higher than those of high-expression groups (p < 0.05). CONCLUSION: Joint detection of CD44v6 and CD62P in the peripheral blood or tissues of NPC patients has diagnostic and prognostic value as a marker of poor clinical outcome.