Malignant Brenner Tumor of the Ovary: A Systematic Review of the Literature.

BACKGROUND: Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. METHODS: We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. RESULTS: After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. CONCLUSIONS: We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.

Combination of weekly topotecan and gemcitabine as a salvage treatment in patients with recurrent ovarian cancer: a phase I study.

BACKGROUND: Evaluation of safety of the weekly intravenous gemcitabine/topotecan combination as salvage treatment in patients with recurrent epithelial ovarian cancer. METHODS: Twenty-four women with histologically-proven relapsed ovarian cancer (ROC) were enrolled in the study. Topotecan (1.75 mg/m2 IV) along with escalated doses of gemcitabine (starting dose 700 mg/m2 with increments of 100 mg/m2) were administered on days 1, 8, and 15 every 28 days. The maximum tolerated dose (MTD) and the dose-limiting toxicity of the combination were evaluated at the first cycle. RESULTS: Twenty-four ROC patients were enrolled in six dose-levels. Most patients had high-grade serous metastatic ovarian cancer (41.7%) and performance status score of 0-1 (95.8%). For 12 patients (50%) treatment was 2nd line and for 12 >2nd line. Eighty-eight cycles were administered with a median of three cycles per patient. The MTD was not reached and grade 3-4 (3.4% and 2.3% of cycles, respectively) neutropenia and grade 4 (3.4% of cycles) thrombocytopenia were the main adverse events. There was no case of febrile neutropenia. Non-hematologic toxicity was mild with grade 2 fatigue being the most frequent complain. The recommended MTD doses of the combination were topotecan 1.75 mg/m2 and gemcitabine 1200 mg/m2 on days 1, 8, and 15 every 28 days. Two complete (8.3%) and three (12.5%) partial responses were achieved (ORR: 20.8%). CONCLUSIONS: The weekly administration of gemcitabine/topotecan regimen in patients with pretreated metastatic ovarian cancer is an active chemotherapy combination, even in heavily pretreated patients, with a manageable toxicity profile which merits further investigation.

Lymphoepithelioma-like breast carcinoma.

Nasopharyngeal lymphoepithelioma is an undifferentiated carcinoma in a dominated lymphoplasma-histiocyte stroma. Lymphoepithelioma-like carcinoma of the breast is the mammary counterpart of the lymphoepithelioma of the nasopharynx and is characterised by proliferation of poorly differentiated malignant cells within a prominent lymphoid infiltrate. It is a very rare primary carcinoma of the breast first reported in 1994 by Kumar and Kumar. Fewer than 40 cases have been reported in the English literature. In this manuscript a case of lymphoepithelioma-like carcinoma of the breast in a 57-year-old patient is reported along with a literature review on this rare entity.

Real-World Data on Health-Related Quality of Life Assessment in Patients With Breast Cancer Receiving Subcutaneous Trastuzumab.

PURPOSE: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (anti-HER2) antibody delivered intravenously, has revolutionized the treatment of patients with breast cancer overexpressing HER2 protein. Recently, a newer subcutaneous formulation was shown to have comparable efficacy to the initial intravenous trastuzumab. In this study, we aimed to evaluate the impact of subcutaneous trastuzumab on the health-related quality of life (HRQoL) of patients diagnosed with early or metastatic HER2-overexpressing breast cancer. METHODS: Patients were provided with the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) and the BR-23 questionnaires. The scoring of questionnaires and patient's sociodemographic and clinicopathologic characteristics were recorded and analyzed by descriptive and correlation statistics employing t test and 2-way analysis of variance. RESULTS: A total of 163 patients agreed to participate in the study. About 90 of 163 patients (55.21%) received subcutaneous trastuzumab and 21 patients intravenous trastuzumab (12.88%). A control group of 52 HER2+ patients received chemotherapy without trastuzumab (31.90%). Patients receiving subcutaneous trastuzumab were older and of more advanced disease stage compared with those receiving chemotherapy (58.5 vs 51 years, 39.8% vs 28.8% advanced disease). In univariate analysis, subcutaneous trastuzumab was associated with less nausea and vomiting (P = .002) but worse cognitive function (P = .013) and dyspnea (P = .042). Patients who have received >8 cycles of subcutaneous trastuzumab reported less diarrhea (P = .049) and systemic therapy side effects (P = .015). Multivariate analysis showed that patients without comorbidity receiving subcutaneous trastuzumab had less treatment side effects, less upset by hair loss, and higher emotional functioning. Of note, mastectomy and subcutaneous trastuzumab were associated with improved role functioning (P = .021). In metastatic disease, no negative impact of subcutaneous trastuzumab on HRQoL was found. CONCLUSIONS: The administration of subcutaneous trastuzumab improved certain symptoms and did not adversely affect most of the assessed functional scales. Particularly, in the metastatic setting, subcutaneous trastuzumab had no negative impact on HRQoL.

Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity.

Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive.

Distinct patterns of angiogenic factor expression as a predictive factor of response to chemotherapy in stage IIIA non-small-cell lung cancer patients.

The expression of various angiogenic factors was assessed in tumour samples of patients with stage III non-small-cell lung cancer (NSCLC) and further evaluated in terms of response to induction paclitaxel-ifosfamide-cisplatin chemotherapy. Freshly isolated lung tumour specimens obtained by bronchoscopy from 70 stage IIIA NSCLC chemotherapy-naïve patients were sampled and analysed for vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3. Microvessel density was assessed through evaluating the angiogenic markers CD34 and CD105. Immunostaining scores were calculated by multiplying the percentage of labeled cells by the intensity of staining for each examined parameter. The overall mean immunostaining score value from all NSCLC samples was 7.83, 5.56 and 15.86 for VEGFR-1, VEGFR-2 and VEGFR-3, respectively. The overall mean value of the endothelial antigen CD34 was 16.29, whereas the expression of the CD105 antigen in endothelial cells yielded a multivariate distribution. Patients who responded to chemotherapy expressed significantly higher VEGFR-1 and VEGFR-3 mean values compared with non-responders (P<0.001). No significant difference was noted in VEGFR-2 mean values between these two groups (P=0.06). The CD34 mean value was significantly higher in responders (P<0.001), whereas there was no significant difference in CD105 expression between the two groups (P=0.07). Angiogenic marker expression proved to be a potential predictive factor of response to chemotherapy in stage III NSCLC. which merits further investigation.

Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer.

Non-small lung cancer (NSCLC) is a lethal malignancy when diagnosed in advanced stage. The evolution of chemotherapy and the development of agents targeting certain molecular pathways involved in tumor progression improved the prognosis. Nintedanib is a new tyrosine kinase inhibitor, which exerts its activity by blocking VEGF, FGF and PDGF receptors and inhibits the angiogenic signaling by preventing receptor dimerization. Several Phase I and II studies proved its safety and efficacy in diverse solid tumors. In patients with advanced NSCLC, the administration of nintedanib may offer an additional chemotherapy benefit in terms of response rate, progression-free survival and overall survival particularly in patients with adenocarcinoma histology, with manageable toxicity. Here, we present an analytical review of literature regarding nintedanib and we focus on its particular importance in NSCLC treatment.

Advanced epithelial ovarian cancer: from standard chemotherapy to promising molecular pathway targets--where are we now?

Ovarian cancer is the most frequent cause of death from gynaecological malignancy in the Western countries, and differences in outcome among different histological subtypes are being increasingly recognized. It is generally considered as chemosensitive, but resistant clones evolve in the majority of cases, at varying rates. In this brief review, we describe advances in conventional chemotherapy, particularly the use of weekly paclitaxel. We then focus on new promising agents that target certain pathways which drive the genesis and evolution of ovarian cancer; these include poly(ADP-ribose) polymerase (PARP) inhibitors targeting tumor cells deficient in homologous recombination. We also discuss other targets including the folate receptor. Ovarian cancer has also proved to be one of the most sensitive types of cancer to an anti-angiogenic approach and we summarize recent experience using a range of agents.

Treatment of patients with metastatic renal cell carcinoma undergoing hemodialysis: case report of two patients and short literature review.

BACKGROUND: Renal cell carcinoma (RCC) may involve both kidneys. When bilateral nephrectomy is necessary renal replacement therapy is mandatory. Treating such patients with sequential therapy based on cytokines, antiangiogenic factors and mammalian target of rapamycin (mTOR) inhibitors is challenging. CASE PRESENTATION: The first case, a 50-year-old Caucasian female, underwent a radical right nephrectomy for RCC. Twelve years later she underwent a radical left nephrectomy along with total hysterectomy including bilateral salpingo-oophorectomy for RCC involving the right kidney and ovary. Hemodialysis was necessary because of bilateral nephrectomy. She relapsed with pulmonary metastases and enlarged mediastinal lymph nodes and received cytokine based therapy along with bevacizumab. Therapy was discontinued despite the partial response because of hemorrhagic gastritis. Therapy was switched to an antiangiogenic factor but the patient manifested a parietal brain hematoma and stopped therapy. Subsequently disease relapsed with malignant pleural effusion and pulmonary nodules and a mammalian target of rapamycin inhibitor was administered which was withdrawn only at patient's deteriorating performance status. The patient died of the disease 13 years after the initial diagnosis of RCC. CONCLUSION: Patients with RCC are in significant risk to manifest bilateral disease. Renal insufficiency requiring hemodialysis poses therapeutic challenges. Clinicians must be aware of the antiangiogenic factors' adverse effects, especially bleeding, that may manifest in higher frequency and more severe in this setting.

DNA ploidy: a prognostic factor of response to chemotherapy and survival in metastatic gastric adenocarcinoma.

BACKGROUND: Metastatic gastric adenocarcinoma confers a dismal prognosis. Several prognostic factors are needed to distinguish patients that will benefit from chemotherapy. In this setting, the prognostic impact of DNA ploidy is still unclear. MATERIALS AND METHODS: The records of 61 patients with metastatic gastric adenocarcinoma were retrospectively reviewed. Response to chemotherapy and overall survival (OS) were assessed and correlated to tumour DNA ploidy index, which was calculated by cytometric image analysis. RESULTS: The median value of DNA ploidy index was 2.3. Patients with a low index responded better to chemotherapy than those with a higher index (p<0.01). Nevertheless, when the median value was used as a cut-off, no significant correlation of DNA ploidy index with response to chemotherapy (p=0.41) or OS (p=0.09) was observed. CONCLUSION: The prognostic role of DNA ploidy in metastatic gastric adenocarcinoma is still debatable. In this study, a low DNA ploidy index was associated with favorable prognosis; however, a suitable cut-off value is not yet available.

Prolonged survival after sequential multimodal treatment in metastatic renal cell carcinoma: two case reports and a review of the literature.

INTRODUCTION: In this case series and short review of the literature, we underline the impact of nephrectomy combined with sequential therapy based on cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors along with metastasectomy on overall survival and quality of life in patients with metastatic clear cell renal carcinoma. CASE PRESENTATION: In the first of two cases reported here, a 53-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer and relapsed with a bone metastasis in his right humerus. He was treated with closed nailing and cytokine-based chemotherapy. For 5 years, the disease was stable and he had great improvement in quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and thorax soft tissue. He was then treated with antiangiogenic factors and mammalian target of rapamycin inhibitors. The disease progressed until September 2009, when he died of allergic shock during a blood transfusion, 9 years after the initial diagnosis of renal cell cancer.In the second case, a 54-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer. A year later, the disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he underwent a metastasectomy. Nine months later, magnetic resonance imaging of his brain revealed a focal right occipitoparietal lesion, which was resected. After two years of active surveillance, the disease relapsed as a pulmonary metastasis and he was treated with an antiangiogenic factor. Further progressions presenting as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine bone metastases were sequentially observed. He then received a first-generation mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a second-generation mammalian target of rapamycin inhibitor and palliative radiotherapy. Ten years after the initial diagnosis of renal cell cancer, his disease is stable and he is on a third antiangiogenic factor and leads an active life. CONCLUSIONS: One multidisciplinary approach to patients with metastatic renal cell cancer combines nephrectomy, metastasectomy, and radiotherapy (when feasible) with medical therapy based on cytokines and targeted treatment employing agents inhibiting angiogenesis, other receptor tyrosine kinases, and mammalian target of rapamycin. This approach could prolong survival and improve quality of life.

Survival in patients with stage IV noncardia gastric cancer - the influence of DNA ploidy and Helicobacter pylori infection.

BACKGROUND: Palliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit. METHODS: The records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis. RESULTS: The median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60-70 vs. 90-100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis. CONCLUSION: Poor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients.

Pancreatic adenocarcinoma-associated polymyositis treated with corticosteroids along with cancer specific treatment: case report.

BACKGROUND: Adenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment. CASE PRESENTATION: We present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2nd line chemotherapy with gemcitabine. CONCLUSIONS: Polymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment.

Sustained complete remission of human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver during long-term trastuzumab (Herceptin) maintenance therapy in a woman: a case report.

INTRODUCTION: This case report and short review discusses how long trastuzumab should be continued in metastatic breast cancer, the safety issues in case of pregnancy and the risk of relapse with trastuzumab cessation. CASE PRESENTATION: We present the case of a 34-year-old Caucasian woman with human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver who achieved prolonged complete remission within six months of receiving trastuzumab (Herceptin) in combination with vinorelbine and gemcitabine. The patient remains in complete remission seven years later and continues to receive trastuzumab as maintenance therapy. CONCLUSION: Trastuzumab-based therapies have greatly improved the survival rates of patients with human epidermal growth factor receptor 2- positive metastatic breast cancer. Despite such improvements, the safety of trastuzumab administration during pregnancy is yet to be defined.

Predictors of survival in stage IV metastatic colorectal cancer.

UNLABELLED: The aim of this study was to evaluate predictors of survival in stage IV metastatic colorectal cancer (CRC). PATIENTS AND METHODS: A total of 541 patients with histologically proven metastatic CRC (UICC stage IV) were retrospectively analysed and 37 variables were tested for their potential relationship to survival. RESULTS: Mean survival time was recorded at 12.8 months [95% confidence interval (CI) 12.0-13.5]. Three factors were independently associated with improved survival: combination chemotherapy, improved performance status and dermatological complications. Eight factors were independently associated with unfavorable survival: worsened performance status, C-reactive protein >5 mg/dl, anemia, anorexia, weight loss > or =10%, fatigue, hypoalbuminemia and blood transfusions. CONCLUSION: A number of factors could be used as predictors of survival in patients with stage IV metastatic CRC. Patients who are relatively fit, have low CRP levels and tolerate combination chemotherapy appear to have a more favorable survival outcome.

Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study.

BACKGROUND: Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration. PATIENTS AND METHODS: Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment. RESULTS: Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3-10.1%] than the remaining (7/317; 2.3%, 95% CI = 0.8-3.3%) (P < 0.012). Specifically, an increased incidence of cardiac-related events was encountered in patients with continuous 24-h 5FU + LV infusion for 5 days (12.5%, 95% CI = 2.3-22.7%) rather than in patients with the same schedule without LV (5.3%, 95% CI = 1.95-8.67%) (P < 0.027), as well as in patients with short 5FU + LV administration (2.4%, 95% CI = 0.9-3.9%) (P < 0.019). Overall, 3/54 patients (5.5%, 95% CI = -0.6-11.1%) on oral capecitabine developed cardiac-related events. Seven out of the 20 patients suffered an acute myocardial infarction, 6 developed ischemia only, while 4 more patients had ECG consistent with coronary vasospasm and 3 with conduction disturbances, of which one subsequently died. Patients administered oral capecitabine had a similar incidence of cardiac-related events; 1/22 (4.5%) patients with advanced breast cancer and 2/32 (6.2%) with colorectal cancer. CONCLUSIONS: The present study supports the toxic effect of 5-FU on the myocardium, which is largely schedule-dependent, whereas a low but finite risk of such toxicity has been observed with oral capecitabine. A high level of alertness is required when using fluoropyrimidines (i.v. 5FU or oral capecitabine), while their toxic effect on the coronary endothelium and myocardium merits further investigation.