BACKGROUND: The study describes the development and implementation of a digital nose database in order to provide patients with nasal prostheses following rhinectomy. Mirrored data for computer-aided design (CAD) cannot...BACKGROUND: The study describes the development and implementation of a digital nose database in order to provide patients with nasal prostheses following rhinectomy. Mirrored data for computer-aided design (CAD) cannot be used due to the unpaired structure of the nose. MATERIALS AND METHODS: The faces of 202 people were digitized using a 3-dimension (3D) scanner. The noses were scaled, measured and classified according to objective criteria. The physician, the patient and the anaplastologist can collaborate in order to select an appropriate nose from the multitude of existing nose types and sizes. Virtual 'fittings' and an individual adaptation of the nose are feasible. For this purpose the epiTecture software was applied. The selected nose is then created on a 3D printer as a thermopolymer model. This model can be fitted and corrected as a physical model on the patient. The remaining steps are identical to conventional prosthesis production. RESULTS: A digital nose database was developed at the University Hospital Dresden with the help of the epiTecture software. Instructions for usage are illustrated using the example of a patient. CONCLUSIONS: The process of providing nasal prostheses described in this paper is different from conventional processes. This is primarily due to the elimination of physical modeling, causing substantially less strain for the patient.
BACKGROUND: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-eff...BACKGROUND: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. CASE REPORT: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. CONCLUSION: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases.
BACKGROUND: Assessment of carbohydrate antigen (CA) 19-9 levels is used for diagnosis and follow-up of pancreaticobiliary cancers, and high levels of this biomarker are suggestive of a malignancy. CA 19-9 may also be ele...BACKGROUND: Assessment of carbohydrate antigen (CA) 19-9 levels is used for diagnosis and follow-up of pancreaticobiliary cancers, and high levels of this biomarker are suggestive of a malignancy. CA 19-9 may also be elevated in patients with conditions other than tumors, such as cholestasis, biliary obstruction, and cholecystitis. CASE REPORT: A 50-year-old male patient presented with jaundice and elevated CA 19-9 levels (161,902 IU/ml). Repeated biopsies of the common bile duct revealed no malignancies. Radiological findings indicated a mass protruding through the common bile duct. Positron emission tomography demonstrated increased (18)F-fluoro2-deoxy-D-glucose uptake in the liver and a mass resembling metastasis was detected. A Whipple procedure was performed and demonstrated no tumor. Postoperatively, CA 19-9 levels decreased to within normal limits (27 IU/ml). CONCLUSION: These results indicate that CA 19-9 levels should not be the sole criterion for a diagnosis of malignancy. Although other analytical tools may aid diagnosis, surgical exploration may be required in some instances to avoid misdiagnosis and determine whether radiological results are falsely positive.
BACKGROUND: Collecting duct carcinoma of the kidney (CDC) is a rare cancer associated with bad prognosis and, at present, with no specific effective therapies. CASE REPORT: We report a clinical case with disseminated hig...BACKGROUND: Collecting duct carcinoma of the kidney (CDC) is a rare cancer associated with bad prognosis and, at present, with no specific effective therapies. CASE REPORT: We report a clinical case with disseminated highgrade CDC presenting with widespread metastasis to both lungs, pelvic bones, axial skeleton, and the central nervous system (posterior fossa, both hemispheres and pituitary-hypothalamic). The primary tumor in the kidney was demonstrated (by fluorescence in situ hybridization and immunohistochemistry with Herceptest (3+ score)) to significantly overexpress HER2. Critically ill at presentation, the patient received oral capecitabine together with double HER2 blockade with both intravenous trastuzumab and oral lapatinib. His clinical response was a dramatic improvement and a progressive decline in the radiological size of all of his multiple cancer lesions. CONCLUSION: Double HER2 blockade is an effective therapy in disseminated CDC even in the presence of brain metastases.
BACKGROUND: Salivary gland tumors (SGTs) are known for their specific heterogeneity and ambiguous outcome for the affected patients. The LKB1 and SMAD4 genes are pivotal components of important signaling pathways, includ...BACKGROUND: Salivary gland tumors (SGTs) are known for their specific heterogeneity and ambiguous outcome for the affected patients. The LKB1 and SMAD4 genes are pivotal components of important signaling pathways, including AMPK and TGF-β. To our knowledge, no study has reported an association between the expression levels of these genes in SGTs. The expression levels of LKB1 and SMAD4 were evaluated to clarify their possible crosstalk in SGTs. MATERIALS AND METHODS: A total of 50 fresh tissue specimens were obtained from patients with SGTs, including pleomorphic adenoma (PA), Warthin's tumor (WT), intermediate grade mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), and carcinoma ex pleomorphic adenoma (CexPA), as well as 8 normal samples. Quantitative real-time polymerase chain reaction was performed for all samples with specific primers. RESULTS: Data were analyzed using statistical methods. PA, WT, MEC, and SDC showed a significant decrease in LKB1 levels, but the gene was up-regulated in CexPA. SMAD4 was overexpressed in all samples. CONCLUSION: The results suggest a possible link between downregulation of LKB1 and overexpression of SMAD4 in SGTs. LKB1 depletion leads to upregulation of SMAD4, promoting epithelial-mesenchymal transition in tumor cells. Therefore, LKB1 and SMAD4 could be key players in inducing tumor heterogeneity in SGTs.
AIM: To investigate the role of delta-like ligand 4 (DLL4) in the angiogenesis of high-grade malignant glioma. MATERIALS AND METHODS: DLL4 expression and microvessel density (MVD) were detected by immunohistochemistry in...AIM: To investigate the role of delta-like ligand 4 (DLL4) in the angiogenesis of high-grade malignant glioma. MATERIALS AND METHODS: DLL4 expression and microvessel density (MVD) were detected by immunohistochemistry in 51 human high-grade malignant glioma tissue samples. The vessel maturation index (VMI) was calculated as the percentage of a-smooth muscle actin (a-SMA)-positive vessels in relation to the amount of CD31-positive vessels. Double fluorescent immunostaining for CD31 and EphrinB2 or EphB4 was performed to identify the arterial (EphrinB2) or venous (EphB4) origins of glioma microvessels. RESULTS: Strong immunostaining of DLL4 and a positive correlation of DLL4 with the MVD were observed in high-grade malignant gliomas. The VMI of the DLL4-positive group was significantly higher than that of the DLL4-negative group. However, no significant association was found between DLL4 and EphrinB2 or EphB4 in high-grade gliomas. CONCLUSION: DLL4 may be an important regulator for vessel proliferation and maturation in human high-grade malignant gliomas.
BACKGROUND: The low incidence and the variable presentation complicate clinical investigations on biliary tract cancer. The results of Valle et al. in 2009 provided, for the first time, an evidence-based palliative treat...BACKGROUND: The low incidence and the variable presentation complicate clinical investigations on biliary tract cancer. The results of Valle et al. in 2009 provided, for the first time, an evidence-based palliative treatment for this rare tumor type. So far no data are available in Germany regarding the current daily care practice. METHODS: We started this national survey in May 2011, including about 3,400 members of the AIO (Working Group Medical Oncology), DGHO (German Society of Hematology and Oncology) and GGHBB (Society of Gastroenterology and Hepatology in Berlin and Brandenburg). The standardized online form contained questions concerning field of action and diagnostic and therapeutic procedures. Evaluation was conducted anonymously. RESULTS: 162 responses could be obtained, corresponding to a response rate of about 5%. 70.4% of the respondents were physicians in hospitals, 23.5% stated to work in private practices. 61.7% of the respondents were medical oncologists and 27.2% gastroenterologists. 52.5% of the participants pointed out to use the standard regimen of gemcitabine and cisplatin. For second-line regimen, the most frequent answer (29%) specified the administration of oxaliplatin in combination with 5-fluorouracil (5-FU) or capecitabine. CONCLUSIONS: This survey may help to clarify the current oncologic daily care procedures for patients with biliary tract cancer in Germany. The results can be helpful for further clinical investigations or the implementation of a tumor-specific register.
BACKGROUND: Severe skin rash as toxicity of erlotinib has been reported in relation to better response and survival. However, some patients require dose reduction due to skin toxicities, and their prognosis remains uncer...BACKGROUND: Severe skin rash as toxicity of erlotinib has been reported in relation to better response and survival. However, some patients require dose reduction due to skin toxicities, and their prognosis remains uncertain. We retrospectively evaluated the clinical course of non-small cell lung cancer patients receiving erlotinib at a reduced dose because of skin rash. PATIENTS AND METHODS: Among 76 patients treated with erlotinib, 55 patients who developed skin rash severer than grade 2 were divided into 2 groups: 24 patients treated with erlotinib with dose reduction because of skin rash (dose reduction group) and 31 patients without any dose reduction (non-dose reduction group). RESULTS: The median progression-free survival in the dose reduction and non-dose reduction groups was 341 and 70 days, respectively, and the median overall survival was 566 and 202 days, respectively (p < 0.001). In the dose reduction group, no smoking history, female sex, epidermal growth factor receptor gene mutation, and grade 3 skin rash were significant baseline factors. CONCLUSIONS: Patients who received erlotinib at a reduced dose following skin rash showed better survival than those without reduction. In cases of intolerable skin rash, patients may benefit from continuous treatment with a reduced dose of erlotinib.
Cetin B, Benekli M, Oksuzoglu B
… +15 more, Koral L, Ulas A, Dane F, Turker I, Kaplan MA, Koca D, Boruban C, Yilmaz B, Sevinc A, Berk V, Isıkdogan A, Uncu D, Harputluoglu H, Coskun U, Buyukberber S
BACKGROUND: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabi...BACKGROUND: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). PATIENTS AND METHODS: A total of 203 patients with HER2+ MBC, who had progressed after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. All patients were treated with the combination of lapatinib (1,250 mg/day continuously) and capecitabine (2,000 mg/m(2) on days 1-14 of a 21-day cycle). RESULTS: The median follow-up was 10.5 months (range 1-38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval (CI) 5-9), with a median overall survival of 13 months (95% Cl 9-17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3-4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. CONCLUSION: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.
BACKGROUND: Although Hodgkin's lymphoma (HL) is a curable cancer, current treatment strategies based on risk stratification and response modulation are not precise enough. The predictive power of biological and morpholog...BACKGROUND: Although Hodgkin's lymphoma (HL) is a curable cancer, current treatment strategies based on risk stratification and response modulation are not precise enough. The predictive power of biological and morphological parameters is controversial, with prognostic models not reaching wide acceptance. PATIENTS AND METHODS: We analyzed the prognostic relevance of 8 parameters in 85 advanced stage classical HL patients, in order to determine whether tissue-based variables could add prognostic value to standard clinical parameters, thus contributing to better risk stratification at presentation. RESULTS: Univariate analysis confirmed 5 indicators of shorter overall survival (OS): Bcl-2 overexpression; increased CD68+ tumor-associated macrophages (TAM); international prognostic score (IPS) > 2; bulky disease; and total lymph node involvement (TLNI) with regard to neoplastic and inflammatory cells. Apart from TLNI, these parameters influenced lower event-free survival (EFS). Multivariate analysis identified 5 independent factors for OS: Bcl-2 overexpression; increased CD68+ TAM; TLNI; IPS > 2; and bulky disease. Increased CD68+ TAM, IPS > 2, and bulky disease affected the EFS. Utilizing the cumulative score of unfavorable prognostic factors for OS, we designed a prognostic model stratifying patients into 4 risk groups (with 0-1, 2, 3, or 4-5 factors), each with progressively reduced OS (p < 0.001). CONCLUSION: Our findings support the combination of tissue-based variables with clinical parameters at diagnosis, identifying patients who are at higher risk of poor outcome.
Costimulatory molecule B7-H4, a member of the B7 family, negatively regulates the immune response of T cells through inhibiting their proliferation, cytokine production and cell cycle. The overexpression of B7-H4 plays a...Costimulatory molecule B7-H4, a member of the B7 family, negatively regulates the immune response of T cells through inhibiting their proliferation, cytokine production and cell cycle. The overexpression of B7-H4 plays an important role in initiation, progression and regression of tumors by promoting malignant transformation of epithelial cells and protecting epithelial cells from anoikis. B7-H4 expression in malignant tumors is useful for clinical diagnosis, and may provide a novel molecular target for cancer treatment.
BACKGROUND: Myeloid sarcoma rarely presents in the absence of systemic myeloid disease. CASE REPORT: In this study, we present a case of intracerebral myeloid sarcoma with no diagnosis of any hematological disease in a 2...BACKGROUND: Myeloid sarcoma rarely presents in the absence of systemic myeloid disease. CASE REPORT: In this study, we present a case of intracerebral myeloid sarcoma with no diagnosis of any hematological disease in a 22-year-old male patient in whom brain magnetic resonance image revealed a meningioma. However, biopsy showed myeloid sarcoma. No myeloid disease was determined. The mass disappeared following 8 cycles of chemotherapy. In the literature, we determined only 8 similar cases cited between 1970 and 2011. CONCLUSION: Intracerebral myeloid sarcoma has currently no standard treatment and may be confused with a primary brain disease. Chemotherapy and/or radiotherapy are the most viable and widely used treatment modalities. Potential occurrence of hematological disease should also be closely followed due to conversion risks.
BACKGROUND: Philadelphia chromosome-positive chronic myeloid leukemia (CML) in children is very rare. CML occurring as a secondary malignancy in individuals treated for diffuse large B-cell lymphoma (DLBCL) is also rare....BACKGROUND: Philadelphia chromosome-positive chronic myeloid leukemia (CML) in children is very rare. CML occurring as a secondary malignancy in individuals treated for diffuse large B-cell lymphoma (DLBCL) is also rare. CASE REPORT: We present the case of a 5-year-old female patient who developed a right orbital mass that was diagnosed as DLBCL. 9 months after receiving treatment for DLBCL, she presented with a white cell count of 250,000/mm(3). Peripheral blood and bone marrow (BM) evaluation revealed a myeloproliferative disorder. Cytogenetic and molecular studies demonstrated the presence of t(9;22). CML following DLBCL has not been previously described in the younger population. To our knowledge, this is the first report of a child who developed a CML as a second malignancy after DLBCL. Therapy-related CML and non-therapy-related secondary CML are discussed as potential explanations of this highly unusual clinical presentation. CONCLUSION: Hematological disorders such as CML may occur after lymphomas. With the increased use of BM cytogenetic studies during staging for lymphoid malignancies, future studies may be able to clarify the question of whether the CML clone in some of these patients existed before treatment for lymphoma.
BACKGROUND: Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have...BACKGROUND: Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to have prognostic relevance. PATIENTS AND METHODS: In order to elucidate new molecular mechanisms underlying these tumors, we carried out a molecular analysis with a genome-wide human high-density single-nucleotide polymorphism (SNP) array, in 9 patients. RESULTS: Single samples showed numerical aberrations on chromosomes (Chrs) 20 and 6 with either trisomy 20 or monosomy 6. No trisomy 8 could be detected. Recurrent heterozygous deletions were found in Chr 5q (including the APC gene locus, n = 3) and Chr 8p23 (n = 4, containing coding regions for the potential tumor suppressor gene CSMD1). This novel deletion in 8p23 showed an association with local recurrence. In addition, structural chromosomal changes (gain of Chrs 8 and 20) were found in a minority of cases. CONCLUSION: The genomic alteration affecting the candidate gene CSMD1 could be important in the development of desmoid tumors.
BACKGROUND: The purpose of this study was to test the hypothesis that the immunohistochemical expression of ERCC1 and RASSF1A would predict both response to and survival after docetaxel and cisplatin combination chemothe...BACKGROUND: The purpose of this study was to test the hypothesis that the immunohistochemical expression of ERCC1 and RASSF1A would predict both response to and survival after docetaxel and cisplatin combination chemotherapy in inoperable or recurrent head and neck squamous cell carcinoma. PATIENTS AND METHODS: A total of 54 patients were treated with frontline systemic chemotherapy composed of docetaxel (60 mg/m(2)) and cisplatin (65 mg/m(2)), every 3 weeks for up to 6 cycles. The expression levels of ERCC1 and RASSF1A were evaluated in the available 36 prechemotherapy samples. RESULTS: The overall objective response rate was 35% (complete remission 12% and partial remission 23%). The median progression-free survival and overall survival (OS) times were 5.0 months (95% confidence interval (CI), 3.7-6.4 months) and 24.2 months (95% CI, 3.5-45.0 months), respectively. The status of low ERCC1 and high RASSF1A expression was an independent favorable prognostic factor for OS in multivariate analysis (p = 0.043; hazard ratio, 7.224; 95% CI, 1.060-49.217). Toxicities were comparable with those of previously reported trials. CONCLUSIONS: Less intensive doses of cisplatin and docetaxel are active but not effective in reducing toxicity. Also, both ERCC1 and RASSF1A might be useful prognostic markers in this regimen.
BACKGROUND: Published data on the association between mouse double minute 2 (MDM2) 309 T/G single nucleotide polymorphism (SNP) and head and neck cancer (HNC) risk are inconclusive. To derive a more precise estimation of...BACKGROUND: Published data on the association between mouse double minute 2 (MDM2) 309 T/G single nucleotide polymorphism (SNP) and head and neck cancer (HNC) risk are inconclusive. To derive a more precise estimation of the relationship, we performed a meta-analysis. MATERIAL AND METHODS: A systematic computerized search of PubMed was performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between the polymorphism and HNC risk. The pooled ORs were performed for TT versus GG, TG versus GG, dominant model (TT+TG vs. GG) and recessive model (TT vs. TG+GG), respectively. RESULTS: A total of 9 studies including 2,755 cases and 4,121 controls were involved in the final meta-analysis. The results of the overall meta-analysis provided some evidence of an association between the polymorphism and HNC risk (OR = 0.82, 95% CI 0.67-0.99 for TG vs. GG). In the subgroup meta-analysis based on the types of tumor, we detected a significantly decreased NPC risk for all genetic models. CONCLUSION: This meta-analysis suggests that the GG genotype of MDM2 SNP309 is associated with HNC risk. The MDM2 SNP309G allele is a highly penetrant risk factor for developing NPC.
BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy. Due to their long survival and subsequently high cumulative doses of bisphosphonates, multiple myelo...BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy. Due to their long survival and subsequently high cumulative doses of bisphosphonates, multiple myeloma patients have the highest risk of developing BRONJ of all patients treated with bisphosphonates. The purpose of the present study was to evaluate the incidence and risk factors for BRONJ in multiple myeloma patients after high-dose chemotherapy and autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: We retrospectively analyzed the data of 120 multiple myeloma patients after high-dose chemotherapy and ASCT treated with bisphosphonates and assessed the incidence and risk factors of BRONJ. RESULTS: Of the 120 patients, 23 (19%) developed BRONJ. 6 patients suffered several BRONJ events, resulting in a total incidence of 23%. The risk for BRONJ was significantly higher for patients with rheumatism and recent dental manipulations. Furthermore, the number of previous bisphosphonate rotations, the duration of bisphosphonate therapy, and the type and cumulative dose of bisphosphonate used were associated with the incidence of BRONJ. CONCLUSION: Our study is the first to determine the risk of BRONJ in a homogeneous group of multiple myeloma patients treated with high-dose chemotherapy and ASCT.
BACKGROUND: This study addresses the association of matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-C (VEGF-C) expression in esophageal squamous cell carcinoma (SCC) with clinicopathologic chara...BACKGROUND: This study addresses the association of matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-C (VEGF-C) expression in esophageal squamous cell carcinoma (SCC) with clinicopathologic characteristics in the patients. MATERIAL AND METHODS: We profiled the expression of MMP-1 and VEGF-C by cDNA microarray in 4 cases and by reverse transcription-polymerase chain reaction (RT-PCR) in 14 cases of esophageal SCC. Another 90 cases were reviewed by immunohistochemical examination of paraffin-embedded sections. RESULTS: Expression of MMP-1 and VEGF-C mRNA in normal esophageal tissue and tumor tissue was compared. Data were fully consistent with the results of RT-PCR. Immunohistochemistry showed that compared to the normal mucosa MMP-1 and VEGF-C protein expression was upregulated in both esophageal atypical hyperplasia (n = 16) and esophageal SCC. Depth of tumor invasion, lymph node metastasis, and clinical stage were directly associated with prognosis in all cases. Furthermore, median overall survival and disease-free survival were significantly shorter in patients with a higher expression of MMP-1 and VEGF-C than in patients with lower expression levels. CONCLUSION: We demonstrated that the expression of both MMP-1 and VEGF-C mRNA and protein was upregulated in esophageal SCC tissues. Protein expression was associated with progressive tumor stage and poor prognosis in patients with esophageal SCC.