Neuroendocrine Neoplasm of the Breast Presenting as a Liver Metastasis: A Rare Diagnostic Challenge.

We present a case of a 58-year-old female who presented initially to an outside institution with abdominal pain and was diagnosed on liver biopsy with a well-differentiated neuroendocrine tumor of an unknown primary source. She was referred to our academic institution for a second opinion after disease progression on the initial chemotherapy regimen. Through additional evaluation, diagnostics, and multi-disciplinary tumor board discussion she was diagnosed with metastases from a well-differentiated neuroendocrine neoplasm of the breast (NENB). Consequently, her treatment plan was modified leading to significant clinical and radiological improvement.

Acquired Gitelman Syndrome Associated with Systemic Sclerosis.

Gitelman syndrome is an inherited renal disorder characterized by hypomagnesemia, hypokalemia, hypocalciuria and metabolic alkalosis linked to the genes encoding the thiazide sensitive NaCl cotransporter (NCCT) located on the distal convoluted tubule of the kidney. It usually presents in late childhood or early adulthood with electrolyte abnormalities resembling chronic thiazide diuretic use. Acquired Gitelman syndrome is a very rare disorder mostly associated with Sjogren's syndrome.

Role of Poly Adenosine Diphosphate Ribose Polymerase Inhibitors in Advanced Stage Ovarian Cancer.

Ovarian cancer is one of the leading causes of death from gynecologic cancers. In this present era of cancer treatment, therapeutic options for patients with advanced or recurrent ovarian cancer are limited. The present standard of care treatment for advanced ovarian cancer is a platinum-based doublet chemotherapy (paclitaxel and carboplatin with or without bevacizumab) after a maximum attempt of surgical cytoreduction. However, there are no promising options for the management of patients with ovarian cancer refractory to the platinum-based chemotherapy. Therefore, newer, safe, and more effective treatment modalities are required for patients with advanced or recurrent ovarian cancer. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have shown an impressive safety profile and anti-tumor efficacy in patients with breast cancer 1 and 2 (BRCA1 and BRCA2) gene-mutated ovarian cancer who were previously treated with the standard of care chemotherapy. We have done a detailed review of the literature to emphasize the role of PARP inhibitors in the treatment of advanced or relapsed ovarian cancer.

Role of Immune Checkpoint Inhibitors in Advanced or Recurrent Endometrial Cancer.

Currently, treatment options for patients with advanced or recurrent endometrial cancer remain limited. The current standard of care treatment for advanced endometrial carcinoma is a platinum doublet chemotherapy. Second-line treatment options overall are very limited. There is no optimal treatment option for patients who show disease progression with first-line therapy. Therefore, novel and more efficacious therapies for patients with advanced or recurrent disease are needed. Immune checkpoint inhibitors have demonstrated a very impressive safety profile and anti-tumor activity in patients with programmed death-ligand 1 (PD-L1) positive endometrial cancer who were pre-treated with chemotherapy. We have done a detailed review of the literature to emphasize the role of immune checkpoint inhibitors in the treatment of metastatic or recurrent endometrial cancer.

Clinical outcomes of African American patients with advanced or metastatic non-small cell lung cancer on Nivolumab in a single community-based cancer center.

African Americans (AA) have the highest incidence and mortality rates with lung cancer. They are diagnosed at an earlier age with more advanced disease. Programmed cell death protein-1 inhibitor, Nivolumab, was approved as a second-line agent after failure of platinum-based therapy for advanced or metastatic non-small cell lung cancer (NSCLC). The original studies leading to the approval of Nivolumab had insufficient AA patients, thus there is still inadequate knowledge on treatment outcomes among AA patients. Our primary study endpoints were to determine the median overall survival, 1-year overall survival rate, median progression-free survival, and 1-year progression-free survival rate of patients with advanced or metastatic non-small cell lung cancer on Nivolumab. Our secondary study endpoints were to determine the overall tumor response rate, median time to response, median duration of response, and incidence of treatment-related adverse events of grade 3 or 4. In this retrospective study, we reviewed the charts of 38 patients, 29 of which were AA, with advanced or metastatic NSCLC who received Nivolumab from March 1, 2015 until November 30, 2017 from a single community-based cancer center and compared our results with historical data. Adenocarcinoma was the most common histology (71%) among all patients. Seven (18%) continued to use Nivolumab while 21 (55%) discontinued the treatment mainly due to progression of the disease. The median overall survival was 21.4 months (95% CI 13.5-27.4) and 17.6 months (95% CI 11.5-27.6) for all the patients and AA, respectively. Both have statistically significant difference (P < 0.001) compared to the historical studies of Borghaei et al. and Brahmer et al. At 1 year, the overall survival rate was 73% (95% CI 50-86) and 66% (95% CI 40-82) for all patients and AA, respectively. The median progression-free survival was also statistically significant (P < 0.001) between all the patients 6.3 months (95% CI 2.8-8), AA 6.0 months (95% CI 2.3-8.0), and the said historical studies. The 1-year progression-free survival rate was 23% (95% CI 10-39) and 28% (95% CI 12-47) for all patients and AA, respectively. Overall tumor response rate which includes complete and partial responses was 21% (95% CI 10-37) and 24% (95% CI 10-43) for all patients and AA, respectively. The median time to response was 3 and 2.8 months for all patients and AA, respectively. The median duration of response was 3.8 and 4.0 months for all patients and AA, respectively. Treatment-related adverse events of grade 3 or 4 were reported in 8 and 10% in all patients and AA, respectively, similar to the rates previously shown. AA patients with advanced or metastatic NSCLC on Nivolumab had increased overall survival and progression-free survival with similar grade 3 or 4 treatment-related adverse events. Providing adequate access to immunotherapy is indispensable to maximize survival benefit for AA patients.

Chimeric antigen receptor T cell therapy in pancreatic cancer: from research to practice.

Chimeric antigen receptor (CAR) T cell therapy is genetically engineered tumor antigen-specific anticancer immunotherapy, which after showing great success in hematological malignancies is currently being tried in advanced solid tumors like pancreatic cancer. Immunosuppressive tumor microenvironment and dense fibrous stroma are some of the limitation in the success of this novel therapy. However, genetic modifications and combination therapy is the topic of the research to improve its efficacy. In this article, we summarize the current state of knowledge, limitations, and future prospects for CAR T cell therapy in pancreatic cancer.

Prospects of chimeric antigen receptor T cell therapy in ovarian cancer.

Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Immunotherapy provides a promising and novel treatment option for ovarian cancer. Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. CAR T cells are genetically engineered T cells with major histocompatibility complex-independent, tumor-specific, immune-mediated cytolytic actions against cancer cells. Initial studies of CAR T cell therapy have shown promising results in ovarian cancer, but there are some obstacles like impaired T cell trafficking, lack of antigenic targets, cytokine release syndrome and most important immunosuppressive tumor microenvironment. Optimization of design, improving tumor microenvironment and combinations with other therapies may help us in improving CAR T cell efficacy. In this review article, we highlight the current knowledge regarding CAR T cell therapy in ovarian cancer. We have discussed basic functioning of CAR T cells, their rationale and clinical outcome in ovarian cancer with limitations.

Metastatic Sternal Osteosarcoma: A Rare Tumor.

Osteosarcoma is the most common primary malignant tumor of the long bones. However, primary osteosarcoma of the chest wall, particularly the sternum, is an extremely rare occurrence. We report a 36-year-old male presenting with a hard, immobile, palpable, anterior chest wall mass. A computed tomographic (CT) scan showed a large destructive anterior mediastinal mass involving the manubrium and sternum with multiple bilateral calcified lung masses, pleural effusions and partially calcified aortopulmonary, right hilar and subcarinal lymphadenopathy. Incisional biopsy of the mass revealed grade 2 chondroblastic osteosarcoma. The patient underwent one cycle of chemotherapy with ifosfamide and palliative radiation. Unfortunately, the patient was unable to tolerate ifosfamide and developed severe nausea and vomiting requiring the discontinuation of chemotherapy. Given his metastatic disease and inability to tolerate standard chemotherapy, he was referred to a comprehensive cancer center for advanced clinical trials.

New drugs and new toxicities: pembrolizumab-induced myocarditis.

Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction. Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis. The treatment was initiated with corticosteroids and guideline-conform heart failure therapy. He demonstrated a marked clinical response with resolution of congestive heart failure symptoms. This article summarises the clinical evidence regarding the epidemiology, pathophysiology, clinical features, diagnostic modalities and management of patients with pembrolizumab-associated myocarditis. In addition, it highlights that programmed death receptor-1 inhibition can cause a spectrum of autoimmune adverse events requiring clinical monitoring and periodic screenings.

Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea.

INTRODUCTION: Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. METHODS: This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. DISCUSSION: Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. FUTURE DIRECTIONS: The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.

Anal Squamous Cell Carcinoma in a Patient with Myasthenia Gravis: Is Immunosuppression the Main Underlying Etiology?

Patients who are immunocompromised by diseases such as human immunodeficiency virus (HIV) infection are more prone to develop some malignancies such as Kaposi's sarcoma and central nervous system (CNS) lymphomas. Historically, anal squamous cell carcinoma (SCC) was also included on the list as an acquired immunodeficiency syndrome (AIDs)-defining cancer.  Similarly, compromised immune disorders including severe immunosuppression, haematologic malignancies, and solid organ transplantation have been identified as important risk factors for the development of anal SCC. Review of the medical literature showed only sporadic cases of anal SCC in patients with pre-existing myasthenia gravis (MG), with or without thymoma.  We present here a case of anal SCC in a patient with several years history of MG who was receiving intravenous immunoglobulin (IVIG).  We believe this association is explained by the autoimmune nature of the disease and the use of immunosuppressive medications to treat it. To further support our case, we also present a review of the literature associating anal SCC with MG.

Lethargy and vision loss: successful management of rhinocerebral mucormycosis.

Rhinocerebral mucormycosis (RCM) is an angioinvasive fungal infection most often caused by Rhizopus oryzae It is usually associated with an underlying risk factor and is associated with a poor prognosis. There are no consensus guidelines on the optimal management of this aggressive disease; most management decisions are based on case reports and expert opinion. We report a successfully managed case of RCM in an insulin-dependent diabetic, initially presenting with a change in mental status, rapidly progressing to complete right eye blindness and ophthalmoplegia and complicated by multiple cerebral infarctions and abscesses. We describe the diagnostic approach and various therapeutic interventions undertaken to successfully manage our patient.