The impact of tamoxifen treatment on voice parameters in premenopausal women with breast cancer.

OBJECTIVE: The study aims to investigate the estrogen-agonistic effects of tamoxifen on voice parameters in premenopausal women diagnosed with breast cancer. METHODS: A total of 108 premenopausal women were included, segmented into distinct treatment groups and a control group. Objective sound analysis was conducted using robust statistical methods, employing SPSS 25.0 for data analysis. RESULTS: The study identified a statistically significant reduction in Jitter values across all treatment groups compared to the control group. No significant changes were observed in other voice quality parameters such as F0, Shimmer, NHR, and HNR. CONCLUSIONS: The findings suggest that tamoxifen may have an estrogen-agonistic effect on voice quality, thereby potentially influencing future treatment protocols. This research fills a critical void in existing literature and sets the stage for more comprehensive studies that consider affects of hormonal therapies to voice.

Brigatinib-associated autoimmune hepatitis: A case report.

INTRODUCTION: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a wide variety of ALK mutations and ROS1 rearrangements. While pancreatic enzyme elevations due to brigatinib are well known, we wanted to present a case that caused liver toxicity. CASE REPORT: ALK and ROS1 translocations were detected in a 58-year-old patient diagnosed with metastatic lung adenocarcinoma. In the patient who had a good response with brigatinib, more than 5-fold elevation was detected in liver enzymes at the fifth month of treatment. MANAGEMENT & OUTCOME: After excluding other hepatitis factors, the patient was thought to have autoimmune hepatitis, and methylprednisolone was started and liver enzymes were decreased. DISCUSSION: Increased creatine kinase and lipase levels are common side effects associated with brigatinib, while liver toxicity is rare. Autoimmune hepatitis due to brigatinib was considered because of hepatic toxicity that developed in the fifth month of treatment and responded well to steroids.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study.

INTRODUCTION: Approximately 20-33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs' solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. RESULTS: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). CONCLUSIONS: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Efficacy of US, MRI, and F-18 FDG-PET/CT for Detecting Axillary Lymph Node Metastasis after Neoadjuvant Chemotherapy in Breast Cancer Patients.

BACKGROUND: The aim of this study was to investigate the efficacy of post-neoadjuvant chemotherapy (NAC) ultrasound (US), magnetic resonance imaging (MRI), and F-18fluorodeoxyglucose positron emission tomography (F-18 FDG-PET/CT) for detecting post-NAC axillary lymph node(ALN) metastasis in patients who had ALN metastasis at the time of diagnosis. METHODS: This study included all breast cancer patients who received NAC for ALN metastasis; underwent axillary assessment with US, MRI, or F18FDG-PET/CT; and then were operated on in the General Surgery Clinic, Adana City Research and Training Hospital, Turkey. Patients' data were recorded, including demographic data, clinicopathological parameters, NAC regimens, and operation types. The axillary response to chemotherapy on post-NAC US, MRI, and F-18 FDG-PET/CT was compared with the postoperative histopathological result of the ALN. RESULTS: The study included a total of 171 female patients. The mean age of the patients was 53.28 ± 10.62 years. The post-NAC assessment revealed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US for detecting ALN metastasis were 59.42%, 82.35%, 82.00%, and 60.00%, respectively, while the same measures regarding MRI for detecting ALN metastasis were 36.67%, 77.78%, 73.33%, and 42.42%, respectively. The sensitivity, specificity, PPV, and NPV of F-18FDG-PET/CT were 47.50%, 76.67%, 73.08%, and 52.27%, respectively. The evaluation of dual combinations of these three imaging techniques showed that the specificity and PPV of the combined use of US and F-18FDG-PET/CT was 100%. CONCLUSIONS: The results showed that US has the highest sensitivity and specificity for detecting ALN metastasis after NAC. Furthermore, ALND may be preferred for these patients instead of SLNB if both examinations simultaneously indicate lymph node metastasis in the post-NAC assessment with US and F-18 FDG-PET/CT. SLNB may be preferred if these two examinations simultaneously show a complete response.

Predictors of Survival in Turkish Patients with Primary Glioblastoma.

AIM: An increasing number of biomarkers of primary glioblastoma (GBM) have recently been described. We aimed to investigate the biological and clinical factors that affect survival in Turkish patients with primary GBM. MATERIAL AND METHODS: The clinical and demographic data of all patients with primary GBM diagnosed between 2007 and 2016 were evaluated. In all the patients? pathological specimens, O6 methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH) 1 mutation were detected retrospectively by immunohistochemistry. Kaplan-Meier survival analysis, log-rank test, and multivariate analyses of the Cox hazard proportional model for all the variables were performed using the SPSS statistical package. The treatment details and other patient-related factors were identified, and their correlations were analyzed. RESULTS: We enrolled 137 primary GBM patients to the study. Median progression free survival (PFS) was 8.57 months (95% CI:6.8-9.5) and median overall survival (OS) was 12 months (95% CI:10.8-13.3). IDH-1 mutations were detected in 21 primary GBMs (15.3%). PFS was 15.43 ± 1.95 months. Survival rates were higher, but no statistically significant difference (p=0.074). MGMT methylation was detected in 40 primary GBMs (29.2%). OS and PFS of MGMT (+) cases were higher than MGMT(-) cases (p=0.001; p=0.001 respectively). Ki67 (%) measurement (10%-90%) average is 32.64 ± 16.56. No statistically significant between higher and lower ki67 levels (p=0.510, p=0.505 respectively). KPS (%) more than 70 at the time of diagnosis statistically significant longer median OS and PFS (p=0.001). PFS and OS were higher in all treatment modalities. CONCLUSION: The most important factors that affected survival were performance score, MGMT methylation status, systemic oncologic therapy, and IDH mutation in the Turkish population with primary GBM. We demonstrated that MGMT methylation and higher KPS levels were associated with significiantly longer OS and PFS.

Extracranial Metastasis of IDH-1 Wild Type Glioblastomas.

AIM: To identify the effects of different immunohistochemical features of glioblastomas with spinal metastases based on the metastatic spread and survival rate. MATERIAL AND METHODS: A total of 214 patients who were diagnosed with and operated for brain tumor in our clinic between 2007 and 2018, and pathologically diagnosed with glioblastoma were retrospectively evaluated. Among them, 141 medical records were reviewed, and 23 of them underwent spinal magnetic resonance imaging postoperatively due to various complaints. RESULTS: All patients with glioblastoma with spinal metastases had negative isocitrate dehydrogenase 1 (IDH-1) in the immunohistochemical examination. The incidence of spinal metastasis is 1.91%. The median Ki-67 index is 30 (range, 4-90; median Ki-67 index: 30+/-18.5). IDH mutation is wild in 55%, mutant in 33%, and not otherwise specified in 12%. Four patients with spinal metastasis has wild-type IDH with mean Ki-67 index of 60, and one of them was a woman (25%) and the remaining three were men (%75), with mean age of 32 years. CONCLUSION: Gliomas with high immunohistochemical proliferation indexes and wild-type IDH with poor prognostic features based on the new classification tended to metastasize to the spine in the early disease stage; therefore, early spinal scanning and radiation therapy might extend the life expectancy. High Ki-67 index and the presence of wild-type isocitrate dehydrogenase may be the predictive factors for spinal screening.

Risk factors for developing cardiotoxicity of trastuzumab in breast cancer patients: An observational single-centre study.

BACKGROUND: Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic. MATERIALS AND METHODS: The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013. RESULTS: A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03). CONCLUSION: The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.

ERCC1 and RRM1 as a predictive parameter for non-small cell lung, ovarian or pancreas cancer treated with cisplatin and/or gemcitabine.

BACKGROUND: We aimed to investigate the impact of RRM1 and ERCC1 expression on response to cisplatin and/or gemcitabine chemotherapy in patients with lung, ovarian or pancreatic cancer. MATERIAL AND METHODS: Patients with lung, ovarian or pancreatic cancer, who used cisplatin and/or gemcitabine therapy were included; hospital files were examined and RRM1 and ERCC1 expression were evaluated with an immunohistochemical method on tissue cross sections from paraffin blocks of the tumour. RESULTS: Out of 89 patients, 51%, 30% and 19% had lung, ovarian and pancreatic cancer, respectively. The response rates to the therapy in patients with lung and ovarian cancer having low ERCC1 expression were 62% and 90%, respectively (p = 0.028 and p = 0.044, respectively). No significant association was found between ERCC1 expression and response to therapy in patients with pancreatic cancer (p = 0.354). Therapeutic response rates in patients with lung and pancreatic cancer with low RRM1 expression were 60% and 82%, respectively. Survival rates were higher in patients with lung cancer in which ERCC1 and RRM1 expressions were low. Median survival duration in patients with ovarian cancer showing low ERCC1 and RRM1 expressions was longer than that seen in patients with high expressions. Although no significant correlation was found between ERCC1 and the survival in ovarian cancer (p = 0.183), there was a significant correlation between RRM1 expression and survival in patients with pancreatic cancer (p = 0.005). CONCLUSIONS: Our results suggest a predictive value of ERCC1 in lung and ovarian cancers, and also RRM1 in lung and pancreatic cancers.

Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the pathogenetic mechanisms and risk factors are not fully understood. The present study evaluated the data of 652 patients with bone metastasis that had undergone treatment with biphosphonates. Subsequently, 24 patients with BRONJ and 20 control patients without BRONJ that were treated with zoledronic acid were enrolled. It was found that BRONJ occurred in 3.6% of patients. The mean age and the administration of dental treatment were found to be significantly associated with BRONJ development (P=0.049 and P=0.013, respectively). The cumulative dose median in the BRONJ group was found to be significantly higher compared with the cumulative dose average in the control group (P=0.037). In addition, at the time of BRONJ development, improvement in the disease was determined to be better in the BRONJ group than in the control group (P=0.031). The present study determined that age, the existence of dental extraction and the cumulative dose of zoledronate were all important risk factors in BRONJ development.

Pancreatic carcinoma, thrombosis and mean platelet volume: single center experience from the southeast region of Turkey.

BACKGROUND: The aim of this study was to investigate the general characteristics of patients with deep vein thrombosis (DVT) and pancreatic cancer as well as evaluate the relationship between mean platelet volume (MPV), DVT and survival. MATERIALS AND METHODS: Seventy-seven patients with pancreatic cancer, who were admitted to Cukurova University Medical Faculty, Department of Medical Oncology, were enrolled in the study RESULTS: The mean age was 59±20. Forty-nine (63.6%) were men and 28 women (36.4%) . Sixty-eight (88.3%) patients had adenocarcinoma and 9 (11.7%) had a malignant epithelial tumor. Thirty-six (46.7%) had liver metastasis at diagnosis. Twenty-six (33.8%) patients were alive, 20 (26%) were dead and in 31 (40.2%) the status was unknown. Only 14 (18.1%) patients had DVT. In 42 (54.5%) patients MPV values were normal, in 28 (36.4%) patients they were above normal, and in 7 (9.1%) patients they were below normal. There was no statistically significant difference between gender, tumour localization, chemotherapy and survival rates (p:0.56, p:0.11, p:0.21). There was no significant difference between DVT, gender, localisation, histological subtype, the presence of metastasis, stage and if the patient had been treated with chemotherapy (p:0.5, p:0.6, p:0.2, p:0.32, p:0.1, p:0.84). There was also no significant difference between MPV and DVT (p:0.57) but there was a significant difference between liver metastasis and DVT (p:0.02). Age, stage, the presence of metastasis and DVT were prognostic in pancreatic cancer patients. CONCLUSIONS: Cases of pancreatic cancer with liver metastasis should be studied more carefully as thrombosis is more common in these patients.

A new approach to the treatment of metastatic paraganglioma: sorafenib.

Paragangliomas are relatively rare chromaffin cell tumors which may be cured through resection. Patients with paragangliomas may develop metastatic diseases. There is no consensus regarding refractory chemotherapy for treatment of metastatic disease. In this report, we presented a case of a 43-year-old woman who was admitted to the hospital with a history of episodic headaches, diaphoresis, and weakness. Elevated plasma catecholamine levels and a right paraaortic mass were observed on computed tomography. The mass was excised, and a diagnosis of paraganglioma was confirmed. After 20 months of follow-up, local recurrence and metastases were detected in the thorax, abdomen, and skeletal system. Plasma and urinary catecholamine levels were high. Chemotherapy was administered, and no improvement was observed. Therefore, following this palliative conventional chemotherapy, sorafenib was administered for three months, and, finally, positron emission tomography showed that the patient's lesions had completely regressed.

Neurofibromatosis type 1, gastrointestinal stromal tumor, leiomyosarcoma and osteosarcoma: four cases of rare tumors and a review of the literature.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1. METHODS: Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section. RESULTS: In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients. CONCLUSIONS: Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1.

Retrospective analysis of neoadjuvant chemotherapy for breast cancer in Turkish patients.

BACKGROUND: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. METHODS: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+, HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. RESULTS: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenopausal and 31 (49.2%) were postmenopausal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. CONCLUSION: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

Retrospective analysis of 498 primary soft tissue sarcomas in a single Turkish centre.

BACKGROUND: Soft tissue sarcomas (STS) must be managed with a team involving pathologists, radiologists, surgeons, radiation therapists and medical oncologists. Treatment modalities and demographic characteristics of Turkish STS were analysed in the current study. MATERIAL-METHODS: Primary adult STS followed between 1999- 2010 in Cukurova University Medical Faculty Department of Medical Oncology were analyzed retrospectively. RESULTS: Of the total of 498 patients, 238 were male and 260 female. The most seen adult sarcomas were leomyosarcoma (23%). Localization of disease was upper extremity (8.8%), lower extremity (24.7%), head-neck 8.2%, thoracic 8%, retroperitoneal 5.6%, uterine 12.4%, abdominal 10%, pelvic region 3.6 and other regions 10%. Some 13.1% were early stage, 10.2% locally advanced, 8.2% metastatic and 12.2% recurrent disease. Patients were treated with neoadjuvant/adjuvant (12%) or palliative chemotherapy (7.2%) and 11.4% patients did not receive chemotherapy. Surgery was performed as radical or conservative. The most preferred regimen was MAID combination chemotherapy in the rate of 17.6%. The most common metastatic site was lung (18.1%). The overall survival was 45 months (95%CI 30-59), 36 months in men and 55 months in women, with no statistically significant difference (p=0.5). The survival rates were not different between the group of adjuvant and palliative chemotherapy (respectively 28 versus 18 months) (p=0.06), but radical surgery at 37 months was better than 22 months for conservative surgery (p=0.0001). No differences were evident for localization (p=0.152). Locally advanced group had higher overall survival rates (72 months) than other stages (p=0.0001). CONCLUSION: STS can be treated successfully with surgery, chemotherapy and radiotherapy. The survival rates of Turkish people were higher in locally advanced group; these results show the importance of multimodality treatment approach and radical surgery.

Capecitabine-induced hypertriglyceridemia and hyperglycemia: two cases.

Capecitabine has shown significant antitumor activity against anthracycline/taxane refractory breast cancer and advanced colorectal carcinoma. The main drug-related adverse effects are palmar-plantar erythrodysesthesia (hand-foot syndrome), diarrhea and stomatitis. Dyslipidemia is a rare but important side effect of this drug. The mechanism of capecitabine-induced hypertriglyceridemia (CI-HTG) is unclear. It may be due to the decreased activities of lipoprotein lipase and hepatic triglyceride lipase. This report is associated with 2 patients who developed severe HTG when receiving capecitabine. Capecitabine was discountinued and antilipemic treatments were given and both cases are in follow-up with normal lipid levels. This report describes CI-HTG and possible pathogenetic mechanisms and the literature is reviewed.

Primary intrapulmonary thymoma associated with myasthenia gravis.

Primary intrapulmonary thymomas are very rare. So far, research in the field has identified only 31 cases. In all databases, a total of two published articles describing primary intrapulmonary thymoma with myasthenia gravis were encountered between 1950 and 2010. We admitted a 58-year-old male patient with a mass in the right lower lobe of his lung. The tumor was excised, and histological findings were found to be consistent with Type AB thymoma. The patient was intubated due to respiratory distress during the postoperative period, and his acetylcholine receptor antibody was determined positive. He was diagnosed with myasthenia gravis. Pyridostigmine therapy and plasmapheresis were scheduled; yet, we could not begin therapy because of rapid deterioration of the patient's respiratory status due to myasthenia gravis and subsequently resulting in intubation-associated pneumonia. The patient's health rapidly worsened, and he died.

Secondary malignancy after imatinib therapy: eight cases and review of the literature.

Chronic myeloid leukemia (CML) is a clonal stem cell disorder, and imatinib is a small molecule inhibitor of Bcr-Abl tyrosine kinase (TK) used in cases with CML. Immediate and short-term side effects of this tyrosine kinase inhibitor (TKI) are well known, but the long-term side effects have not yet been clearly identified. Although an increased risk of secondary cancer in cases treated by imatinib was not found in two large series, secondary malignancies have been reported in some cases using TKIs, and this issue is important in daily clinical practice for clinicians. Here we report eight cases with neoplasias that developed during imatinib therapy and review secondary malignant disorders occurring during/after imatinib treatment.

Analysis of PTEN, VEGF, HER2 and P53 status in determining colorectal cancer benefit from bevacizumab therapy.

BACKGROUND: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. MATERIALS AND METHODS: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. RESULTS: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). CONCLUSIONS: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

Loss of CD20 antigen expression after rituximab therapy of CD20 positive B cell lymphoma (diffuse large B cell extranodal marginal zone lymphoma combination): a case report and review of the literature.

Rituximab (the chimeric anti-CD20 antibody) is widely used in the treatment of CD20 positive non-Hodgkin's lymphoma (NHL). The response rate at relapse after repeated use in prior CD20 positive responders is lower than 50%. Several mechanisms can be responsible for rituximab resistance. CD20 negative relapses which transformed from CD20 positive aggressive and indolent forms of lymphoma can be the one of the reason of secondary resistance to rituximab. The authors report a case with combination of aggressive and indolent form of lymphoma who relapsed after 7 months from the last dose of rituximab therapy. CD20 transformed negative from positive in her relapsed disease. Patients with CD20 positive B cell NHL must rebiopsy after first line rituximab therapy if their disease relapsed or progressed.