Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population.

A review of obesity, insulin resistance, and the role of exercise in breast cancer patients.

Breast cancer, the most common female malignancy in the world, has a strong association with obesity and insulin resistance. The importance of these risk factors goes up significantly in patients already affected by this cancer as they negatively affect the prognosis, recurrence rate, and survival by various mechanisms. The literature on the role of physical activity and aerobic exercise on modifying the above risks is debatable with data both for and against it. In this article, we have reviewed the risks of obesity and insulin resistance in breast cancer patients and the controversy associated with the impact of exercise. Ultimately, we have concluded that a randomized control trial is necessary with an individualized aerobic exercise program for a minimum duration of 20 wk on breast cancer patients, who are undergoing or recently completed chemotherapy, to study its effects on insulin resistance, weight, and clinical outcome.

CML in pregnancy: A case report using leukapheresis and literature review.

Chronic myelogenous leukemia (CML) complicating pregnancy is uncommon. Literature search demonstrates only a few case reports and some case series but large studies are lacking due to its uncommon presentation. Management of these patients is particularly challenging due to limited available options as several chemotherapy drugs could potentially lead to adverse outcomes and fetal malformations. Leukapheresis has been used in these situations; however paucity of data exists regarding the outcome and complications associated with the procedure. Using leukapheresis alone for extended period to manage CML during pregnancy is also rare. Here we report a case of CML complicating pregnancy which was successfully managed utilizing leukapheresis, followed by a review of literature addressing this controversial issue.

Serotonin syndrome after the use of tramadol and ziprasidone in a patient with a deep brain stimulator for Parkinson disease.

Serotonin syndrome (SS) is a life-threatening adverse reaction that can result from the therapeutic use of serotonergic drugs or accidental drug interactions. Tramadol is a drug that is widely prescribed because of its low abuse potential, but physicians need to be aware of its significant potential to cause SS because it inhibits serotonin reuptake. Ziprasidone is an atypical antipsychotic that can also cause dangerous interactions to cause SS because it is not only a potent 5-HT1A agonist but also has been reported to inhibit serotonin reuptake with an affinity similar to tricyclic antidepressants, in addition to inhibiting reuptake of norepinephrine. We are describing the clinical characteristics of a gentleman with bipolar disorder and Parkinson disease who presented with SS, despite having a deep brain stimulator in the subthalamic nucleus, which decreases central serotonin levels, and a discussion of the factors that contributed to his presentation.

Age old dapsone in the treatment of idiopathic thrombocytopenic purpura--a case report with review.

Idiopathic thrombocytopenic purpura (ITP) is characterized by premature platelet destruction in the reticuloendothelial system due to the presence of autoantibodies against the platelet membrane proteins. Patients who are resistant to the traditional treatment options that include the administration of steroids, IV immunoglobulin, and antirhesus D immunoglobulin and the performance of a splenectomy are diagnosed to have refractory chronic ITP. Management options in these patients are not well defined. Long-term steroids, rituximab, danazol, azathioprine, and cyclophosphamide have variable efficacy and at the same time carry significant side effects. We present the case of a patient treated effectively with dapsone, a drug that is much safer than other drugs and which can be used before resorting to splenectomy; we also include a review of the literature establishing its role in the management of ITP.

Comparing newer oral anti-platelets prasugrel and ticagrelor in reduction of ischemic events-evidence from a network meta-analysis.

The two newer antiplatelet drugs, prasugrel and ticagrelor have both been incorporated in various national guidelines and are both under consideration for approval or have already been approved by various drug regulatory authorities. Mortality benefits with clopidogrel were comparable to newer anti-platelets, and prasugrel had great anti-ischemic potency than ticagrelor. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2012 that assessed clinical outcomes with prasugrel or ticagrelor. The comparator was standard dosage of clopidogrel. Outcomes assessed were the risk of all causes mortality, TIMI non-CABG major bleeding, and a composite of stent thrombosis, recurrent ischemia and serious recurrent ischemia in the intervention groups versus the comparator groups. Event rates were compared using a forest plot of relative risk using a random effects model (Mantel-Haenszel); and Odd's ratio was calculated in the absence of significant heterogeneity. Prasugrel was indirectly compared with ticagrelor using network meta-analysis. Four studies (total N = 34,126) met the inclusion/exclusion criteria. Both drugs had improved mortality and greater risk of bleeding compared to clopidogrel; but outcomes were comparable for both (p = NS). However a composite of recurrent ischemic events, including rates of stent thrombosis (p = 0.045) was reduced to a modest degree with prasugrel compared with ticagrelor. This systematic review suggests greater clinical efficacy of both prasugrel and ticagrelor compared with clopidogrel and an indirect comparison indicates prasugrel may be more effective than ticagrelor for preventing stent thrombosis and recurrent ischemic events.

Treatment of multidrug resistant advanced alveolar soft part sarcoma with sunitinib.

Sunitinib is a tyrosine kinase/angiogenesis inhibitor with proven efficacy in gastrointestinal stromal tumor and advanced renal cell carcinoma. We are presenting the case report of a patient with aggressive alveolar soft part sarcoma with lung and bone metastases, who had failed multiple chemotherapy regimens showing significant response to sunitinib. There was not only complete regression of the primary tumor, stabilization of his bone metastases and significant improvement in the quality of life. Our report shows that sunitinib has the capability of playing a pivotal role in the management of non-gastrointestinal stromal tumors like alveolar soft part sarcoma. Further research and trials must be encouraged over the use of this drug as it is most definitely promising.

Metastatic renal extraskeletal Ewing sarcoma in complete remission for the last 8 years.

Primary renal extraskeletal Ewing sarcoma (EES) is rare but well known to be aggressive, less responsive to the treatment, and has early predilection for metastases. Metastases at the time of diagnosis to the lungs or bones are associated with poor outcome. We present a case of primary renal EES in 57-year-old woman with multiple metastases to the lungs at the time of diagnosis with complete remission of the disease for the last 8 years following multimodality treatment Multidisciplinary approach for the management of EES has definitely improved the quality of life and the survival of the patients.

A case report of complete remission of pulmonary metastases from epithelioid sarcoma to navelbine chemotherapy.

Management of soft tissue sarcomas can be very challenging because they have a high rate of metastasis, especially to the lungs, and respond very poorly to the currently available chemotherapeutic drugs. We present a case of epithelioid sarcoma in which complete remission of pulmonary metastases was observed after treatment with a single agent, navelbine, a vinca alkaloid, and a potential therapeutic agent. The patient has been persistently free of metastases for 4 years since treatment with navelbine. Further studies are warranted to establish the role of navelbine for the treatment of soft tissue sarcoma and their metastases.

Chemotherapy versus surgery in primary B-cell lymphoma masquerading as Klatskin tumor-a diagnostic and therapeutic dilemma.

Primary lymphoma in the region of the liver bed mimicking hilar cholangiocarcinoma or Klatskin tumor is very rare. A patient presented with obstructive jaundice along with right upper quadrant pain, weight loss, and decreased appetite. Apart from altered liver function, her lactate dehydrogenase was significantly elevated, and imaging studies showed prominent lesion close to the liver bed with localized lymphadenopathy. The diagnosis ultimately reached at by biopsy and immunohistochemical staining was diffuse large B-cell lymphoma. Such cases are very infrequent, but demand awareness. The sooner the diagnosis can be reached by minimally invasive procedures, the earlier chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone can be initiated and laparotomy can be avoided as chemotherapy is the mainstay of treatment, even in the presence of jaundice.

Acute dyspnea from treatment of AL amyloidisis with bortezomib.

Bortezomib with or without dexamethasone has been reported to be very effective and well tolerated in the treatment of AL amyloidosis. Commonly reported adverse effects are fatigue, nausea, vomiting, diarrhea, constipation, postural hypotension from autonomic neuropathy, peripheral neuropathy, thrombocytopenia and anemia. Dyspnea has been rarely reported as an adverse effect of bortezomib therapy in AL amyloidosis. We are reporting three case reports of patients suffering from AL amyloidodis, who had new onset acute dyspnea secondary to bortezomib treatment that required drug discontinuation. There might be some correlation between the AL amyloidosis disease and bortezomib associated dyspnea, but the pathophysiology is poorly understood.

Gastrointestinal stromal tumor with primary resistance to imatinib and extensive bone metastases.

Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial tumors of gastrointestinal tract characterized by mutations activating c-KIT or platelet-derived growth factor receptor alpha. GISTs frequently metastasize to liver and peritoneum, but rarely to the bones. Imatinib, a tyrosine kinase inhibitor, has revolutionized the treatment of advanced and metastasized GISTs by both slowing down the disease progression and prolonging the survival. Occasionally, patients with GISTs can develop primary or secondary resistance to imatinib monotherapy. We are presenting an interesting case of metastatic GISTs with extensive bone lesions and primary resistance to imatinib. Efforts to identify bone metastases using appropriate imaging modalities are highly recommended in patients diagnosed with GISTs. Also, alternate strategies to overcome the emerging resistance with single agent imatinib chemotherapy are warranted.

CNS Hemangiopericytoma: A Systematic Review of 523 Patients.

BACKGROUND: Central nervous system (CNS) hemangiopericytomas are rare mesenchymal tumors of the brain. In the absence of randomized clinical trials or large studies, the only information we have about the natural history and the management is from isolated clinical case series. They have suggested that surgery is beneficial, with conflicting results on the role of complete resection and adjuvant radiation. We have conducted a systematic review of clinical case series of CNS hemangiopericytoma analyzing the biology of the tumor and the best follow-up and management strategy. METHODS: Fifteen pertinent clinical case series on newly diagnosed CNS hemangiopericytoma were selected by a review of literature. A total of 523 patients were analyzed for age, sex, mode of recurrence and metastases, and survival after complete/incomplete resection with or without radiation. RESULTS: The mean age was found to be 44.17 (±3.59) years. The incidence was higher in male individuals younger than 45 years and in older female individuals. Complete resection and adjuvant radiation significantly improved survival in comparison with incomplete resection and no radiation, respectively (P<0.0001). Furthermore, a significant trend of the tumor to recur locally compared with extraneural and neural axis metastases was noted (P<0.0001). The mean time for distant metastases was seen to be 91.33 (±12.66) months. CONCLUSIONS: Complete resection followed by adjuvant radiation improves survival. Extraneural metastases, especially to lung, bone, and liver, are not uncommon and can occur late in the disease course for which continued follow-up is required. There is also a need to establish a systemic treatment regimen to control the distant metastases.

Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States.

BACKGROUND: Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC) based on the outcomes in ABC-02 trial. Multiple factors can affect outcomes in these patients. This retrospective review evaluates the University of Cincinnati experience with GC in advanced intrahepatic (IHC)/extrahepatic cholangiocarcinoma (EHC) and gall bladder carcinoma (GBC). METHODS: In this study approved by University of Cincinnati IRB, retrospective analysis of advanced BTC patients seen between 01/2008 and 01/2015 was done. Kaplan Meyer method was used to calculate progression free survival (PFS), and overall survival (OS). Cox model was used to test the association between baseline variables and OS/PFS, adjusting for gender and age at diagnosis. Patients were identified using ICD code for BT tumors, 26 patients met inclusion criteria: histologically proven advanced BTC that received GC as their initial chemotherapy. GC was given as per ABC-02 protocol with appropriate modifications until disease progression or unacceptable toxicities. RESULTS: Median age at diagnosis was 62 years (range, 31-81 years). Eighteen (69%) were IHC, 5 EHC, 3 GBC, 61% male, 73% whites. Performance status (PS): 0-1: 69%, PS 2: 31%. Baseline CA19-9 data was available for 21 patients, (range 1 to 69,543), and abnormal CA19-9 was seen in 14 patients (54%). PFS was 4.5 months (95% CI: 3.1-8.9 months) and OS was 10.5 months (95% CI: 7.9-18.8 months). OS at 6 and 12 months was 69% (18/26) and 42% (11/26). Thirty-eight percent (10/26) received 2nd line chemotherapy, of these 9/10 received 5FU based chemotherapy. Eleven percent (3/26) received 3rd line chemotherapy. Increase in baseline carcinoembryonic antigen (CEA), alanine aminotransferase, alkaline phosphatase (ALP) and total bilirubin was associated with increased risk of death while increase in baseline CEA and ALP was associated with increased risk of progression (P valve <0.05). In the group of patients who had all three major risk factors (PS ≥2, CEA >3, and stage IVb), the median survival was 2.9 months (95% CI: 2.6-9.3 months), which was significantly worse compared to rest of the population [median 18 months (95% CI: 5.4-19.5 months), P<0.01]. CONCLUSIONS: Our data supports the use of GC as a first line regimen for advance BTC in a non-clinical trial setting. Results are comparable to those reported in ABC-02 trial, despite inclusion of PS 2 patients whom constituted 31% of our population. In the patient population studied, baseline CEA and liver function test appeared able to predict response to GC in advanced BTC. Patients with all three high risk factors (PS ≥2, CEA >3, and stage IVb) did poorly and may need careful selection prior to initiating chemotherapy.

Influence of Rituximab on Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma and Role of Prophylaxis--A Systematic Review of Prospective Studies.

Despite the improvement in overall survival in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, the occurrence of central nervous system (CNS) relapse heralds a very poor prognosis. The evidence is conflicting on the incidence and pattern of CNS relapse in the rituximab era compared with before the rituximab era and on the role of CNS prophylaxis. We conducted a systematic analysis of the data from 7 prospective studies, studying the incidence and type of CNS relapse, the role of prophylaxis, and survival after CNS relapse, with and without rituximab-based chemotherapy. No statistically significant difference was found in the incidence of CNS relapse with the use of rituximab-based chemotherapy compared with CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], prednisone) chemotherapy. Leptomeningeal disease was more common and the survival after CNS disease was better in the rituximab era. No difference was found in the incidence of isolated CNS relapse. Chemoprophylaxis significantly decreased the incidence of CNS recurrence. The use of rituximab has not influenced the incidence of CNS relapse compared with the use of CHOP. Chemoprophylaxis plays a significant role in high-risk patients with DLBCL in decreasing CNS recurrence. Large randomized clinical trials are warranted to differentiate between intrathecal and systemic chemoprophylaxis.

Prophylactic CNS directed therapy in systemic diffuse large B cell lymphoma.

Overall survival in diffuse large B-cell lymphoma (DLBCL) has significantly improved in the last decade, especially after the incorporation of rituximab. Involvement of the central nervous system (CNS) at presentation or at recurrence is an uncommon event, but carries a dismal prognosis with median survival of less than 6 months. Although prophylactic CNS directed therapy is a widely used approach to prevent this complication, randomized clinical trials have been very limited. CNS prophylaxis has inherent toxicities; therefore, identifying the population of patients who would receive most benefit is of utmost importance. From an extensive review of current literature, we report the incidence of CNS relapse in DLBCL and describe the role of CNS prophylaxis in the post-rituximab compared to the pre-rituximab era. We also review the current modalities of CNS prophylaxis and attempt to identify the high-risk patients who would benefit. Lastly, we present a treatment algorithm that defines the role of CNS prophylaxis in the management of patients with DLBCL.

A case of multiple myeloma with metachronous chronic myeloid leukemia treated successfully with bortezomib, dexamethasone, and dasatinib.

The coexistence of multiple myeloma and chronic myeloid leukemia in a single patient is a very rare event that has been reported very infrequently in the literature. We report a case of a patient who developed chronic myeloid leukemia four years after his diagnosis with multiple myeloma. Historically, no link between the two malignancies has been identified. This synchronous existence complicates the treatment plan for these patients, and there is a lack of evidence on the best therapeutic approach. Our patient was successfully treated with a combination of bortezomib, dexamethasone, and dasatinib, which he tolerated well for eleven months until he eventually succumbed to cardiac complications and pulmonary hypertension leading to his death.

Durable response with a combination of imatinib and sorafenib in KIT exon 17 mutant gastrointestinal stromal tumor.

Imatinib, a selective KIT tyrosine-kinase inhibitor is considered standard first line therapy in metastatic gastrointestinal stromal tumors (GISTs). However, up to 40-50% of patients develop resistance to imatinib resulting in progression of disease. Other kinase inhibitors such as sunitinib, and most recently regorafenib have been approved as second and third line options respectively. Sorafenib has also been used following progression on standard therapies. Here we present the case of a patient with stage IV GIST of the rectum who had a rare exon 17 mutation treated prior to the approval of regorafenib. Therapy initially consisted of single agent imatinib, followed by sunitinib then sorafenib. Following continued progression of disease, the patient went on to develop stable disease for close to two years on a combination of sorafenib and imatinib.

Medulloblastoma in an Adult With Late Extraneural Metastases to the Mediastinum.

Background. Medulloblastoma, although the most common brain tumor of childhood, is exceedingly rare in adults. These tumors have a propensity for local recurrence and to metastasize along the leptomeninges; however, extraneural metastases are very rare and typically occur in the bone or bone marrow. We have not come across any case in literature of medulloblastoma with mediastinal metastases in an adult. Case Presentation. We report a case of medulloblastoma in a 38-year-old lady who was treated with surgery followed by craniospinal radiation. Ten years later she presented with hoarseness from true vocal cord paralysis. She was diagnosed to have infiltrating metastases of her medulloblastoma to the mediastinum, which was confirmed by biopsy. There was no local recurrence. This was treated with chemotherapy followed by stem cell rescue, and she remained progression free for 2 years. Conclusion. Medulloblastomas are rare in adults and can present with late extraneural metastases following treatment. Although most common reported sites are bone and bone marrow, late metastases to other unexpected areas like the mediastinum are possible too and warrant awareness. This can be treated with chemotherapy followed by high-dose chemotherapy and stem cell rescue in a young patient with good performance status.