Hereditary Thrombophilia Testing Among Hospitalized Patients: Is It Warranted?

Background Hereditary thrombophilias (HTs) are a group of inherited disorders that predispose the carrier to venous thromboembolism (VTE). It is estimated that 7% of the population has some form of HT. Although testing for HT has become routine for many hospitalized patients, knowing when to order the tests and how to interpret the results remains challenging. In the United States, there are no clear guidelines regarding testing for HT. We conducted a study to evaluate the utilization of HT testing among hospitalized patients to examine its impact on immediate management decisions and overall cost burden. In addition, we discuss the common reasons for healthcare providers to order these tests and review the data behind these reasons in the literature. Methodology A retrospective analysis of 2,402 patients who underwent HT testing between February 1, 2016, and January 31, 2018, was conducted. Eligible patients had at least one HT test ordered during hospitalization. The primary outcome was to determine the incidence of positive actionable tests. A positive actionable test was defined as a positive result that changed the anticoagulation intensity, type, or duration. Patients with a history of previous VTE, ongoing medical conditions requiring life-long anticoagulation, or unprovoked VTE were considered non-actionable. Results Among the 2,402 patients, 954 patients met the inclusion criteria with a mean age of 54 years. A total of 397 (41.6%) tests were ordered for acute VTE, while the rest were for non-VTE conditions, such as stroke, pregnancy complications, peripheral artery diseases, and others. Only 89 positive tests were actionable (14% of the positive tests, and 9.3% of the total ordered tests). There was a statistically significant association between increasing age and having both a positive test result (p = 0.006) and an actionable test (p = 0.046). The total cost of ordering these tests was estimated to be $566,585. Conclusions HT testing in the inpatient setting did not alter management in many cases and was associated with increased healthcare costs. The decision to order these tests should be individualized based on the clinical scenario.

Prognostic Impact of Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma: Data from a Large Population-Based Database.

PURPOSE: Cytoreductive nephrectomy (CN) was considered a well-established treatment modality for patients with metastatic renal cell carcinoma (RCC) in the interferon era. However, its role after the introduction of multiple targeted therapies is less well established. Herein, We evaluated the effect of CN on overall survival (OS) on patients with RCC who were identified through the Surveillance, Epidemiology, and End Results database (SEER). MATERIALS AND METHODS: A total of 5,483 patients with metastatic RCC were identified from 2010 to 2016 using the SEER database. Factors pertaining to the following variables were collected: presence or absence of CN; age; gender; grade; status of metastasis to bone, liver, lung and brain; tumor stage; nodal status; histological subtypes; and chemotherapy status. Subjects who had CN were matched with those who did not in all previously mentioned covariates using inverse probability weighting. These weights were then used in adjusted Cox regression models to report doubly robust estimates. RESULTS: CN was associated with 67% reduction in the hazards of death. Advanced T-stage, N1 disease, advanced tumor grade, non-clear histology and metastasis to bone, liver, lung or brain are independent risk factors for death. Patients with T4 disease benefited less of CN compared to those with T1 disease, while higher number of metastatic sites didn't predict worse outcome among those who had CN. CONCLUSION: CN could provide a survival advantage in favorable risk patients with RCC in the era of targeted therapy.

Prostate Adenocarcinoma with Brain Metastasis: A Surveillance, Epidemiology, and End Results Database Analysis 2010-2015.

BACKGROUND Prostate adenocarcinoma rarely metastasize to the brain. The aim of this study was to understand the risk association and survival outcomes comparing prostate cancer with brain metastasis (group 1) with prostate cancer without brain metastasis (group 2) at the time of initial diagnosis. MATERIAL AND METHODS We searched the Surveillance, Epidemiology, and End Results (SEER) statewide cancer registries for all cases of stage IV prostate cancer adenocarcinoma diagnosed between 2010 and 2015. We used the Kaplan-Meier method and Cox regression to analyze survival outcomes and logistic regression to study the association between the presence of brain metastasis and potential risk variables. Exclusion criteria were the presence of neuroendocrine and small cell histology. RESULTS The study included 14 753 patients. Of these, 187 patients were in group 1 (with brain metastasis) and 14 566 were in group 2 (without brain metastasis). When comparing the metastases distribution at the time of initial presentation between group 1 and group 2, the occurrence of bone metastasis was similar in the 2 groups (87% vs 90%); however, liver metastasis (13% vs 4%) and lung metastasis (29% vs 7%) were significantly higher in group 1. We found a strong association between brain metastasis and visceral metastasis. There was no association between age, race, and grade and having brain metastasis. CONCLUSIONS Our analysis shows that visceral metastasis is associated with a higher risk of brain metastasis. Presence of a visceral metastasis can be a useful parameter to consider early magnetic resonance imaging of the brain to facilitate diagnosis of asymptomatic brain metastasis.

Prognostic impact of Philadelphia chromosome in mixed phenotype acute leukemia (MPAL): A cancer registry analysis on real-world outcome.

Mixed phenotype acute leukemia (MPAL) is thought to have poor outcome, and presence of the Philadelphia chromosome (Ph+) has been considered to be an adverse prognostic marker. However, most of these reports were in the pre-tyrosine kinase inhibitors (TKIs) era. Recent limited reports indicate improved outcomes for MPAL with the addition of TKIs. We examined the outcomes of 241 cases of MPAL according to the 2008 WHO classification from the Surveillance, Epidemiology, and End Results registry. The MLL+ patients had a median age of 6 years while other subtypes occurred mostly in adults and had comparable age. On multivariate analyses and after adjustment for age, year of diagnosis and chemotherapy status, Ph+ MPAL patients had reduced risk of death in comparison to Ph(-) MPAL patients (hazard ratio [HR] = 0.28, P = .002). So, MLL+ MPAL had the worst outcome with a 10-fold increased risk of death in comparison to Ph+ MPAL patients (HR = 10.2, P < .001). Importantly, the outcome of Ph+ MPAL was comparable to Ph+ acute lymphoblastic leukemia in a 1:1 matched case-control analysis. In conclusion, this is the largest registry study which examines the outcomes of MPAL subtypes. We confirm that MPAL is a heterogenous disease. Note, Ph+ MPAL nowadays has a better OS in comparison to other subtypes and is comparable to Ph+ ALL patients. This is most likely secondary to changes in practice and more utilization of TKIs. On the other hand, MLL rearrangement is associated with infantile MPAL and has a dismal prognosis.

Factors Associated with Worse Outcome in Early Stage Gastric Cancer Using the Surveillance, Epidemiology, and End Results (SEER) Database.

Background The benefit of adjuvant treatment in gastric adenocarcinoma patients with involvement of the muscularis propria but not beyond is unclear. We aim to establish a model that identifies the factors that adversely affect the prognosis in these patients. Methods We used the Surveillance, Epidemiology, and End Results (SEER) database to identify subjects with stage T2aN0M0 gastric adenocarcinoma who had tumor resection between 2004 and 2015. Data pertaining to the following variables were collected: age, gender, ethnicity, tumor size, grade, site, number of lymph nodes (LNs) being examined, and extent of surgery. Results A total of 1307 patients met our inclusion criteria. The five-year overall survival (OS) was 65%. The following factors were significantly associated with a shorter OS in univariate analysis. Age > 60 years, non-Hispanic whites and non-Hispanic blacks, patients with less than 15 lymph nodes examined at the time of surgery, tumors at the fundus and cardia of the stomach, and those who underwent endoscopic resection or had partial esophagectomy. On multivariate Cox regression, the following factors were predictors for worse OS: age > 60 years with a hazards ratio (HR) = 2.03 (95% CI: 1.49-2.76), patients with less than 15 lymph nodes examined with HR = 1.72 (95% CI: 1.34-2.20), non-Hispanic whites and non-Hispanic blacks with HR = 1.62 (95% CI: 1.26-2.08), and tumors within the cardia and fundus of the stomach with HR = 1.51 (95% CI: 1.21-1.89). Conclusion Patients with stage T2aN0M0 gastric cancer who had their tumor located at the cardia or fundus of the stomach or those with inadequate lymph nodes resection had inferior survival and could potentially benefit from adjuvant chemotherapy.

Acute undifferentiated leukemia: data on incidence and outcomes from a large population-based database.

Acute undifferentiated leukemia (AUL) is rare and defined by the absence of bona fide myeloid and lymphoid markers. Little is known about its incidence, survival and optimal management in the recent time period. Based on a case observed in our clinic, we queried the Surveillance, Epidemiology, and End Results database between 2000 and 2016. A total of 1,888 cases of AUL were diagnosed (1.34 per million person-years). The incidence of AUL has significantly decreased over time. Compared to other acute leukemias, patients with AUL have the highest median age (74 years); in contrast to acute myeloid leukemia (AML, 65) and acute lymphoblastic leukemia (ALL, 12). Excluding patients with preexisting malignancies, 1,444 patients with AUL were analyzed for survival. Only 35% of AUL patients had received chemotherapy. Comparatively, 94% of ALL and 71% of AML cases received chemotherapy. Among AUL patients who received chemotherapy, the median survival was 12 months as opposed to 1 month in the group who did not receive chemotherapy (or unknown status). Among adults, AUL patients had the worst prognosis, with a median overall survival (OS) of 9 months, compared to 27 months in ALL and 13 months in AML. Among children, the median OS was superior for all three groups of leukemias, the OS of AUL patients being better than in AML and very similar to ALL. On multivariate analysis, older age and time period were associated with worse outcome. We describe here the largest series of cases with AUL published to date.

Erratum to "Association of Tissue Transglutaminase Antibody Titer with Duodenal Histological Changes in Children with Celiac Disease".

[This corrects the article DOI: 10.1155/2016/6718590.].

Cladribine in the remission induction of adult acute myeloid leukemia: where do we stand?

The combination of cytarabine and an anthracycline has been the standard of care for the induction of remission in acute myeloid leukemia (AML). The response to treatment and survival of adult patients with AML are still variable and depend on multiple factors. Therefore, there have been many efforts to improve the response to treatment and survival rates by either increasing the cytarabine dose or adding a third agent to the standard induction chemotherapy regimen. Unfortunately, attempts to improve response and survival have been mostly unsuccessful. Recent clinical trials and retrospective studies explored the addition of cladribine to standard induction chemotherapy for AML. Some of these studies showed higher rates of complete remission, and one showed improved survival. In this review, we will discuss the antileukemic properties of cladribine and summarize the recent clinical data regarding its incorporation into the induction therapy for adult AML.

Posterior reversible encephalopathy syndrome while receiving irinotecan with fluorouracil and folinic acid for metastatic gastric cancer.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome with seizures, headache, altered mental status and visual disturbances. It is typically associated with posterior cerebral white matter oedema on neuroimaging. There is an increasing number of cases of PRES reported with different chemotherapeutic protocols. However, PRES is rarely reported in association with irinotecan, fluorouracil and folinic acid (FOLFIRI). We report a 28-year-old female patient with a history of Stage IV gastric cancer who presented with abdominal pain and recurrent vomiting that was thought to be related to a partial intestinal obstruction secondary to peritoneal metastasis. Eventually, she was treated with FOLFIRI. A few hours after initiation of the fluorouracil infusion in the second cycle, she developed a tonic-clonic seizure. MRI of the brain showed multiple bilateral T 2 and flair hyperintense cortical and subcortical lesions suggestive of PRES. Other causes of PRES were excluded, as well as brain metastasis. Unfortunately, the patient developed septic shock and died a few days after her presentation.

Clostridium difficile infection in oncology patients: epidemiology, pathophysiology, risk factors, diagnosis, and treatment.

Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. Its incidence has been increasing in the recent years despite preventative measures. CDI increases annual expenses by 1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, as explained by their frequent exposure to risk factors. CDI in cancer patients is associated with higher mortality rates and prolonged hospitalization. Furthermore, CDI affects the course of the disease by delaying treatments such as chemotherapy. Chemotherapeutics drugs are considered independent risk factors for CDI. This review discusses Clostridium difficile infection in cancer patients, including those who are receiving chemotherapy. Herein, we summarize recent data regarding the epidemiology, risk factors, including chemotherapy regimens, pathogenesis, diagnostic techniques and treatment options, including newer agents. Method: A literature search was performed using the PubMed and Google Scholar databases. The MeSH terms utilized in different combinations were 'clostridium difficile', 'neoplasia/cancer/oncology', 'chemotherapy', 'diagnosis', and 'treatment', in addition to looking up each treatment option individually to generate a comprehensive search. The articles were initially screened by title alone, followed by screening through abstracts. Full texts of pertinent articles (including letters to editors, case reports, case series, cohort studies, and clinical trials) were included in this review.

Hemophagocytic Lymphohistiocytosis Complicating Systemic Sarcoidosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by histiocyte proliferation and hemophagocytosis. Primary HLH is caused by genetic defects, whereas secondary HLH occurs in the setting of underlying diseases, such as infections, malignancies, or rheumatic diseases. Rheumatic diseases, such as systemic juvenile arthritis or systemic lupus erythematosus, have been associated with HLH. However, the association between sarcoidosis and HLH has been rarely reported in the literature. Herein, we report a case of a 36-year-old female who was recently diagnosed with sarcoidosis, and she developed fatal HLH that was not responsive to high-dose steroids.

Trastuzumab-associated Posterior Reversible Encephalopathy Syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome that presents with neurological manifestations, including seizures, headache, or confusion, and is associated with posterior cerebral white matter edema on imaging. PRES is typically a benign and reversible condition. However, PRES can be fatal or associated with permanent deficits. Numerous conditions are associated with PRES, including hypertensive encephalopathy, renal diseases, and cytotoxic or immunosuppressant drugs. Recently, many case reports described the association between PRES and chemotherapeutic agents. However, trastuzumab-associated PRES is rarely reported. Herein, we report a case of a 51-year-old female with a history of metastatic gastric cancer who developed seizures while being treated with trastuzumab, and neuroimaging confirmed the diagnosis of PRES.

A Case of Multiple Myeloma Associated with Extramedullary Plasmacytoma of the Gallbladder Manifesting as Acute Cholecystitis.

Multiple myeloma (MM) is a common hematological malignancy that represents 1% of all cancers. MM is distinguished from other plasma cell disorders by prominent bone marrow involvement and systemic organ damage. Extramedullary plasmacytomas of the gall bladder (GB) or biliary ducts, whether solitary or in association with MM, are very rare. We report a case of a 66-year-old female with a history of refractory MM who presented with right upper quadrant abdominal pain. Her laboratory evaluation revealed an abnormal liver panel and lactic acidosis. Abdominal ultrasonography was consistent with acute cholecystitis with no evidence of biliary obstruction or abnormal liver parenchyma. An open cholecystectomy with liver biopsy was performed. The histological evaluation revealed involvement of the GB submucosa and serosa, as well as the liver parenchyma by abnormal plasma cells with lambda light chain restriction. Congo red stain for the GB sample was positive. The patient declined further treatment for MM and was discharged home with comfort measures.

Intrahepatic Cholangiocarcinoma Masquerading as Acute Fatty Liver of Pregnancy: A Case Report and Review of the Literature.

Cholangiocarcinoma (CCA) is an uncommon cancer and accounts only for 3% of all gastrointestinal malignancies. In this report, we present a case of an intrahepatic cholangiocarcinoma masquerading as acute fatty liver of pregnancy (AFLP). A 38-year-old female who is 36-week pregnant presented with a 1-week history of headache, nausea, vomiting, and right upper abdominal pain, along with hepatomegaly. Laboratory investigations were remarkable for mild leukocytosis, hyperbilirubinemia, proteinuria, and elevated transaminases and prothrombin time. Ultrasound of the liver revealed hepatomegaly, fatty infiltration, and a right hepatic lobe mass. Based on the overall picture, AFLP was suspected, and the patient underwent delivery by Cesarean section. However, bilirubin and liver enzyme levels gradually increased after delivery. MRI revealed a large dominant hepatic mass along with multiple satellite lesions in both lobes. Biopsy revealed the presence of intrahepatic CCA. CCA presenting during pregnancy is extremely rare with only 9 other cases reported in the literature. Therefore, the signs and symptoms can be easily confused with other more common disorders that occur during pregnancy.

Achalasia after bariatric Roux-en-Y gastric bypass surgery reversal.

Achalasia is a rare esophageal motility disorder that is characterized by a loss of peristalsis in the distal esophagus and failure of lower esophageal sphincter relaxation. The risk of developing esophageal motility disorders, including achalasia, following bariatric surgery is controversial and differs based on the type of surgery. Most of the reported cases occurred with laparoscopic adjustable gastric banding. To our knowledge, there are only three reported cases of achalasia after Roux-en-Y gastric bypass and no reported cases after revision of the surgery. We present a case of a 70-year-old female who had a previous history of Roux-en-Y gastric bypass with revision. She presented with persistent nausea and regurgitation for one month. Esophagogastroduodenoscopy showed a dilated esophagus without strictures or stenosis. A barium study was performed after the endoscopy and was suggestive of achalasia. Those findings were confirmed by a manometry. The patient was referred for laparoscopic Heller's myotomy.

Gastric Metastasis from Renal Cell Carcinoma, Clear Cell Type, Presenting with Gastrointestinal Bleeding.

Renal cell carcinoma (RCC) accounts for 80-85% of all primary renal neoplasms. Although RCC can metastasize to any organ, gastric metastases from RCC are exceedingly rare. A 67-year-old male presented with melena and acute blood loss anemia. The patient had a history of RCC that had been treated with a radical nephrectomy. He had a recent myocardial infarction and was receiving double antiplatelet therapy. After hemodynamic stabilization, esophagogastroduodenoscopy showed a polypoid mass in the gastric fundus. The mass was excised. Histological and immunohistochemical evaluation were consistent with clear cell RCC. The polypoid lesion is consistent with a late solitary metastasis.

BRAF V600Q-mutated lung adenocarcinoma with duodenal metastasis and extreme leukocytosis.

Driver mutations in patients with non-small cell lung cancer (NSCLC) can lead to distinct behaviors and patterns of metastasis. Mutations in the proto-oncogene B-raf (BRAF) occur in approximately 3% of NSCLC cases. In the literature, reports of patients with lung adenocarcinomas metastasizing to the duodenum are rare, and most of the only 21 cases reported were from before the advent of next-generation sequencing. We present here a case involving a 57-year-old female who had a lytic lesion in her lesser trochanter. Biopsy showed metastatic adenocarcinoma of lung origin. Chest X-ray showed a large left upper lobe mass. Next-generation sequencing analysis confirmed the presence of BRAF V600Q mutation. The patient presented with persistent anemia and melena. Esophagogastroduodenoscopy confirmed the presence of duodenal metastasis. She also had suspected paraneoplastic leukemoid reaction. To our knowledge, this is only the second well-documented case of gastrointestinal metastasis from BRAF-mutated lung cancer.

Gastric Metastases from Lung Adenocarcinoma Causing Gastrointestinal Bleeding.

Metastases to the stomach are rare. They are commonly asymptomatic, and the diagnosis is usually established during autopsy. We present a patient known to have stage IV lung adenocarcinoma who presented with melena and shock. Endoscopy revealed multiple gastric nodules, which were proved to be metastatic deposits from her lung cancer. The possibility of gastric metastases should be kept in mind in patients presenting with gastrointestinal bleeding. Endoscopy and biopsy remain the gold standard for diagnostic testing in such patients.

Intussusception: a rare complication in a patient with acute leukaemia after consolidation chemotherapy.

Intussusception is telescoping of one segment of the gastrointestinal tract into an adjacent one. It is more common in children than adults. When it occurs in adults, it is usually associated with a lead point. Intussusception is very rare in acute leukaemia and has only been reported in few cases. We present a case of an adult woman who presented with intussusception after a cycle of consolidation chemotherapy with high-dose cytarabine for acute myeloid leukaemia. Other causes of acute abdominal pain were excluded, and the diagnosis was established by CT scan of the abdomen and barium enema. No pathological lead points were found intraoperatively. She underwent a right-sided hemicolectomy with complete recovery. To the best of our knowledge, this is only the fourth case of intussusception that has been reported in an adult patient with acute myeloid leukaemia.