90Yttrium Ibritumomab Tiuxetan (Zevalin) for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Report of 5 Cases.

Radioimmunotherapy (RIT) with radio-labeled monoclonal antibodies to CD20 produces a high response rate in patients with low-grade B-cell lymphomas. The use of this modality in patients with chronic lymphocytic leukemia (CLL) has been sporadic in clinical trials and was hampered by the extensive marrow involvement seen commonly in patients with CLL, which would produce a high risk for marrow aplasia after treatment with RIT. Herein, we report our experience with RIT in 5 patients with CLL or SLL showing short-lived responses and significant myelosuppression. After 90Y-ibritumomab tiuxetan treatment, the median time to relapse was 65 days, and no cases of MDS or AML were observed during follow-up. All patients experienced grade ≥3 thrombocytopenia and neutropenia, with median durations of 39.5 days and 107 days, respectively.

Overall survival of patients with cHL who progress after autologous stem cell transplant: results in the novel agent era.

In the pre-novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time from posttransplant progression to death or last follow-up. Of 1158 patients who underwent ASCT, 367 had progressive disease. Median age was 34 years (range, 27-46) and 192 were male. Median PPS was 114.57 months (95% confidence interval [CI], 91-not achieved) or 9.5 years. In multivariate analysis, increasing age, progression within 6 months, and pre-ASCT positive positron emission tomography scan were associated with inferior PPS. When adjusted for these features, patients who received CPI, but not BV, as first treatment for post-ASCT progression had significantly higher PPS than the no CPI/no BV group (hazard ratio, 3.5; 95% CI, 1.6-7.8; P = .001). Receipt of allogeneic SCT (Allo-SCT) did not improve PPS. In the era of novel agents, progressive cHL after ASCT had long survival that compares favorably with previous reports. Patients who receive CPI as first treatment for progression had higher PPS. Receipt to Allo-SCT was not associated with PPS in this population.

Impact of perioperative chemotherapy on survival outcomes among patients with metastatic colorectal cancer to the liver.

Aim: Compare overall survival (OS) between adjuvant and neoadjuvant chemotherapy and analyze the effect of chemotherapy on OS. Materials & methods: National Cancer Database was queried for patients diagnosed with metastatic colorectal adenocarcinoma with isolated liver metastases between 2004 and 2016. We evaluated the OS and chemotherapy effect using Kaplan-Meier estimates and multivariable cox regression analyses. Results: Total 6883 patients with metastatic colorectal cancer and liver metastases were included, of which 6042 patients were treated with surgery and chemotherapy and 841 patients were treated with surgery only. Patients who received neoadjuvant chemotherapy had better OS compared with patients who received adjuvant chemotherapy. Conclusion: Patients with colorectal cancer with isolated liver metastases who were treated with neoadjuvant chemotherapy had better OS compared with adjuvant chemotherapy.

The role of surgery in small differentiated thyroid cancer.

INTRODUCTION: The incidence of small, differentiated thyroid cancer (DTC) cases has been increasing in the United States and the world mainly due to incidental detection because of widespread use of diagnostic modalities. While the option of active surveillance instead of surgical resection is getting more popular, there is still an open discussion about the best approach in these cases. MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with non-metastatic small T1/N0 DTC between 2004 and 2016, who have known surgical status and Charlson comorbidity index of two or less. We evaluated the overall survival (OS) based on the surgery status using Kaplan-Meier estimates and multivariable cox regression analyses. RESULTS: A total of 98,501 patients with non-metastatic small DTC were included, within which 96,612 (98.1%) were treated with surgery, and 1889 (1.9%) were not treated with surgery or other ablative modalities. We found that patients who were treated with surgery had better OS compared to patients who were not treated with surgery (mean OS 171 months vs 134.1 months, P < 0.001, median OS was not reached). This difference was still statistically significant even after we used propensity score matching for age, gender, race, Charlson-Deyo score, tumor size, and histology. On multivariate analysis, surgery was associated with better OS (HR 0.218; 95% CI: 0.196-0.244; P < 0.001). Same trend was found in subgroup analysis when we split the cohort according to tumor size (<1 and ≥1 cm), histology (follicular, papillary and Hurthle cell carcinoma), and age (<55 years vs ≥55 years). CONCLUSION: Patients with non-metastatic small DTC who were treated with surgery had significant improvement in OS compared to patients who were not treated with surgery. Notwithstanding the limitations of the current analysis, these results call for caution prior to recommending routine surveillance for all patients with small DTC.

Clinical Characteristics and Survival Outcomes of Primary Effusion Lymphoma: A National Cancer Database Study.

INTRODUCTION: Primary effusion lymphoma (PEL) is a rare HHV8(+) non-Hodgkin lymphoma associated with HIV infection or other causes of immunosuppression. Large-scale studies describing the natural history of this entity are lacking. MATERIALS AND METHODS: National cancer database (NCDB) was queried for patients diagnosed with PEL between 2004 and 2016. All patients age ≥ 18 years diagnosed with PEL were included. We excluded patients with multiple primary malignancies or lost follow-up. Kaplan-Meier and multivariate cox regression were used in the analyses. RESULTS: Of the 219 PEL patients included in the analysis, 179 (82%) were males, 161 (74%) Caucasian and 49 (22%) African American. Median age at diagnosis was 60 ± 19 years and median OS (mOS) was 8.5 months. One hundred and fifteen were HIV+, 63 HIV-, 111 received chemotherapy, and 101 did not. Patients who received chemotherapy had better mOS compared to patients who did not receive chemotherapy (13 vs. 3 months, P < .001). This difference was observed in HIV+ patients (22.97 vs. 1.97 months, P = .006), but not in HIV- patients (6.24 vs. 8.20 months, P = .752). On multivariate analysis, chemotherapy treatment was associated with better OS (HR 0.502 95% CI 0.324-0.777; P = .002), whereas HIV status did not affect the OS (HR 0.6 95% CI 0.3-1.4; P = .258). CONCLUSION: This largest retrospective analysis on PEL revealed that current chemotherapeutic approach is significantly beneficial for HIV+ patients but not for HIV- patients. The rapid advancement in HIV treatment might be playing a role in survival improvement among HIV+ patients. Novel therapies are needed to improve the survival of patients with PEL, especially in HIV- patients. MICROABSTRACT: PEL is a rare HHV8(+) non-Hodgkin lymphoma. Using national cancer database, we studied clinical characteristics, and outcomes of 219 PEL patients. We found that chemotherapy significantly improved overall survival in HIV+ patients. However, a similar survival improvement was not seen in HIV- patients. Significant improvement in efficacy of antiretroviral therapy is likely contributing to the survival improvement in HIV+ patients.

Controversial risk factors for cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma is a rare malignancy accounting for 3% of gastrointestinal cancers in the USA. While multiple risk factors for cholangiocarcinoma are established, other potential risk factors are still controversial. Herein, we used a large national database to investigate possible risk factors and associations. METHOD: We used the National Inpatient Sample database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of cholangiocarcinoma. Using multivariate logistic regression analysis, we assessed the association between obesity, alcohol abuse, smoking, diabetes mellitus and cholangiocarcinoma. RESULTS: Out of 30 9552 95 admissions, 20 030 had cholangiocarcinoma. Cholangiocarcinoma patients were older (67 ± 12.8 vs. 57 ± 20.6; P < 0.001) and had fewer female patients (48 vs. 59%; P < 0.001). Multivariate logistic regression analysis showed that diabetes mellitus was associated with cholangiocarcinoma (OR, 1.04; 95% CI, 1.01-1.08; P < 0.001). On the other hand, alcohol, smoking and obesity were all inversely associated with cholangiocarcinoma (OR, 0.75; 95% CI, 0.69-0.81; P < 0.001), (OR, 0.75; 95% CI, 0.71-0.79; P < 0.001) and (OR, 0.71; 95% CI, 0.67-0.75; P < 0.001), respectively. In addition, compared to Whites, Hispanic and Asian/Pacific Islander races were more associated with cholangiocarcinoma (OR, 1.27; 95% CI, 1.21-1.34) and (OR, 1.79; 95% CI, 1.67-1.92) (P < 0.001 for all), respectively, whereas African American race was inversely associated with cholangiocarcinoma (OR, 0.85; 95% CI, 0.81-0.89; P < 0.001). CONCLUSION: Patients with a diagnosis of diabetes mellitus or from certain ethnic groups (Hispanic and Asian/Pacific Islander) are associated with increased risk for cholangiocarcinoma.

Studying the association between breast cancer and renal cell carcinoma.

PURPOSE: There are case reports of patients with both primary breast cancer (BC) and renal cell carcinoma (RCC). We explore the association between these two malignancies using SEER population data and our institutional records. METHODS: We studied the association between BC and RCC in the 2000-2016 Surveillance, Epidemiology, and End Results (SEER) database. We then reviewed our hospital records of patients with both BC and RCC and collected information including personal and family history of cancers, genetic testing, and patient outcomes. RESULTS: Of the 813,477 females diagnosed with BC in the SEER database, 1914 later developed RCC. The risk of developing RCC was significantly increased within the first 6 months, 7-12 months, and 1-5 years following BC diagnosis with standardized incidence ratios (SIRs) of 5.08 (95% CI 4.62-5.57), 2.09 (95% CI 1.8-2.42), and 1.15 (95% CI 1.06-1.24), respectively. Of 56,200 females with RCC, 1087 later developed BC. The risk of developing BC following RCC was elevated within the first 6 months (SIR of 1.45 [95% CI 1.20-1.73]). For our hospital patients, 437 had both BC and RCC. 427 (97.71%) were female, and 358 (81.92%) were white, and breast cancer was diagnosed before RCC in 246 (56.3%) patients. There were 15 germline mutations in those with genetic testing. CONCLUSION: Our findings suggest that BC patients are at higher risk of developing RCC and vice versa. BC tended to precede RCC, and patients frequently had personal histories of other malignancies and a family history of cancer, particularly, BC.

Prognostic and predictive value of microsatellite instability status among patients with colorectal cancer.

Objectives: Compare overall survival (OS) between microsatellite instability (MSI) high and MSI-stable and analyze the effect of chemotherapy on OS. Methods: National cancer database was queried for patients diagnosed with colorectal adenocarcinoma between 2010 and 2016. We evaluated the OS and the chemotherapy effect using Kaplan-Meier estimates and multivariate Cox regression analyses. Results: Total of 30,436 stage II patients and 30,302 stage III patients were included. In stage II with high-risk features and MSI-high, patients who received chemotherapy had better OS compared to patients who didn't receive chemotherapy. The same was found in stage II with no high-risk features and MSI-high group. Conclusion: Stage II colorectal cancer patients with high-risk features and MSI-high who received chemotherapy have better OS compared to patients who didn't receive chemotherapy.

The impact of gender and HPV status on anal squamous cell carcinoma survival.

BACKGROUND: Anal cancer is a rare entity and the effect of gender and HPV status on survival is controversial. We aimed to evaluate the difference in overall survival (OS) according to gender and analyzed the effect of HPV status on OS. PATIENTS AND METHODS: The National Cancer Database (NCDB) was queried for patients with anal squamous cell carcinoma between 2004 and 2016. We evaluated the OS based on gender and HPV status using Kaplan-Meier estimates and we used multivariate Cox regression analyses to evaluate factors associated with overall survival. RESULTS: A total of 6133 patients with known HPV status were included for analysis. In the non-metastatic group, male gender was associated with worse OS (HR 1.50, 95% CI 1.32-1.70; P<0.001) whereas HPV status did not affect the OS (HR 1.08, 95% CI 0.96-1.22; P=0.213). In the metastatic group, there was no difference in OS based on gender (HR 1.29, 95% CI 0.91-1.82; P=0.148), whereas HPV-negative status was associated with worse OS (HR 1.52, 95% CI 1.09-2.12; P=0.014). CONCLUSION: Females had better OS only in non-metastatic anal squamous cell carcinoma (ASCC). HPV-negative status was associated with worse OS only in metastatic ASCC.

Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related deaths in the world with an estimated number of 1.8 million new cases and about 881,000 deaths worldwide in 2018. The epidemiology of CRC varies significantly between different regions in the world as well as between different age, gender and racial groups. Multiple factors are involved in this variation, including risk factor exposure, demographic variations in addition to genetic susceptibility and genetic mutations and their effect on the prognosis and treatment response. In this mini-review, we discuss the recent epidemiological trend including the incidence and mortality of colorectal cancer worldwide and the factors affecting these trends.

The Epidemiology of Pancreatic Cancer and the Association With Acetylsalicylic Acid in the United States: A Population-Based Study.

OBJECTIVES: Pancreatic cancer (PaC) is the third leading cause of cancer-related death in the United States. Multiple studies have investigated the epidemiology and the association between PaC and acetylsalicylic acid (ASA) use, revealing mixed results. Using a large database, we sought to investigate the epidemiology of PaC. METHODS: Using a commercial database (Explorys Inc, Cleveland, Ohio), which includes electronic health record data from 26 major integrated US health care systems, all patients 18 years and older diagnosed with PaC for 5 years were identified based on Systematized Nomenclature Of Medicine-Clinical Terms. We determined the prevalence of PaC and the potential associated factors using univariable and multivariable analysis. RESULTS: Of the 32,970,850 individuals, we identified 30,250 individuals with PaC with an overall prevalence of 0.08%. Individuals with PaC were more likely to be males, seniors (age, >65 years), and White, compared with patients without PaC. In subgroup analysis of chronic pancreatitis, individuals on ASA, individuals >65 years, White, and White males were less likely to have PaC, and non-White females were more likely to have PaC. CONCLUSIONS: This is the largest population-based study evaluating the epidemiology of PaC. We observed a protective association of ASA on a subgroup of patients with PaC and chronic pancreatitis.

Association of non-alcoholic fatty liver disease and polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women. Women with PCOS have androgen excess as a defining feature. They also have increased insulin resistance and obesity, which are also risk factors for non-alcoholic fatty liver disease (NAFLD). However, published data regarding PCOS as independent risk factor for NAFLD remain controversial. Therefore, we conducted this study to evaluate the association between PCOS and NAFLD using a large national database. METHODS: We identified adult female patients (≥18 years) with PCOS using the National Inpatient Sample database between 2002 and 2014. The control group included patients who did not have a diagnosis of PCOS. Multivariate logistic regression analysis was performed to study the association of NAFLD with PCOS. RESULTS: Out of a total of 50 785 354 women, 77 415 (0.15%) had PCOS. These patients were younger (32.7 vs 54.8; p<0.001) and more likely to be obese (29.4% vs 8.6%; p<0.001) compared with non-PCOS patients. However, the PCOS group had less hypertension (23.2% vs 39.8%), dyslipidaemia (12% vs 17.8%) and diabetes mellitus (18.1% vs 18.3%) (p<0.001 for all). Using multivariate logistic regression, patients with PCOS had significantly higher rate of NAFLD (OR 4.30, 95% CI 4.11 to 4.50, p<0.001). CONCLUSION: Our study showed that patients with PCOS have four times higher risk of developing NAFLD compared with women without PCOS. Further studies are needed to assess if specific PCOS treatments can affect NAFLD progression.

New paradigms in the treatment of low-risk thyroid cancer.

INTRODUCTION: Thyroid cancer is the most common endocrine malignancy. Multiple different staging systems have been introduced and used for differentiated thyroid carcinoma (DTC). AREAS COVERED: In this literature review we provide an overview of the standard options for management of patients with low risk differentiated thyroid cancer. EXPERT OPINION: Surgery is considered the first and most important step in managing DTC with goal to remove all the malignant foci in order to achieve cure and increase the survival with least chance of recurrence. Many studies have been conducted to determine the best surgical approaches and how aggressive surgeries should be in order to achieve the best outcomes regarding efficacy as well as safety. Radioactive iodine (RAI) therapy has also been a part of the treatment regimen and is used for different purposes with three main goals: post-surgical ablation, adjuvant therapy and persisted/recurrent disease treatment. Radiation therapy, on the other hand, is still not recommended to be used routinely in DTC because of the conflicting data of its benefit.

Clinical outcome of patients diagnosed with myelodysplastic syndrome-unclassifiable (MDS-U): single center experience.

Myelodysplastic syndrome unclassifiable (MDS-U) is a small subtype of myelodysplastic syndromes (MDS). However, rare literature exists in terms of natural progression and clinical outcome of patients with MDS-U. In the present study, we investigated the characteristics and the clinical outcomes of patients categorized as MDS-U based on 2008 World Health Organization criteria (WHO) in a single center comparing to other MDS groups. Out of eight hundred and two patients who met WHO criteria for MDS at our institution, ninety patients (11%) were initially classified as MDS-U. Upon pathological review, only half of the cases were confirmed to be MDS-U. With follow up, half of the MDS-U cases were reclassified to another subtype. We found neither significant difference in median overall survival nor in risk of transformation to acute myeloid leukemia when comparing MDS-U to other MDS groups. Additional larger studies are needed to confirm our results.

A Curious Case of Proximal Muscle Weakness with Eosinophilic Polymyositis.

Eosinophilic polymyositis (EPM) is part of a rare disorder, eosinophilic myopathies (EM), which is a form of polymyositis characterized by the presence of eosinophils in muscle biopsy sections and occasionally blood eosinophilia. Herein, we are presenting an interesting case of eosinophilic polymyositis presenting with muscle pain with no other organ systems involved.

Challenges in Treating Secondary Syphilis Osteitis in an Immunocompromised Patient with a Penicillin Allergy: Case Report and Review of the Literature.

Syphilis is a sexually transmitted infection that remains fairly commonplace. The introduction of penicillin aided in curbing the incidence of disease; however, with the advent of the human immunodeficiency virus (HIV), syphilis is now on a resurgence with sometimes curious presentations. We present a case of a 36-year-old Caucasian gentleman with untreated HIV who complained of a skin eruption and joint pains for 6 weeks, prompting the diagnosis of secondary syphilis osteitis. Skin lesions were reminiscent of "malignant" syphilis. CD4 count was 57 cells/µL. RPR was elevated with 1 : 64 titer and positive confirmatory TP-PA. Radiography of the limbs revealed polyostotic cortical irregularities corroborated on bone scintigraphy. The patient had an unknown penicillin allergy and was unwilling to conduct a trial of penicillin-based therapy. He was subsequently treated with doxycycline 100 mg twice daily for 6 weeks and commenced antiretroviral therapy, noting dramatic improvement in both the skin lesions and joint pains. Unfortunately, he defaulted on follow-up, precluding serial RPR and bone imaging. Penicillin allergies have proven to be quite a conundrum in such patients, without much recourse for alternative therapy. Doxycycline with/without azithromycin is other options worth considering.

Prior hypomethylating agent use lacks impact on clinical outcome in patients with secondary acute myeloid leukemia arising from myelodysplastic syndromes treated with standard induction chemotherapy.

Patients with secondary acute myeloid leukemia (sAML) arising from prior myelodysplastic syndromes have poor prognosis. Anthracycline plus cytarabine (7 + 3) is a standard treatment option for patients who are fit for intensive therapy. In the present study, 22 of 96 sAML patients (23 %) were treated with 7 + 3 and achieved median overall survival (OS) of 9.8 months. Hypomethylating agents (HMA) were given for MDS in 6/22 (28 %) of the patients. When evaluating the prior HMA group, CR/CRi was 50 % for those with prior HMA exposure and 63 % for those without HMA exposure (P = 0.6). Median OS was 14 months for prior HMA exposure vs 10 months for no prior HMA (P = 0.9). The outcome of sAML patients who were treated with 7 + 3 continues to be poor. No statistical significant difference was found between response rates and mOS between prior HMA exposure or not. Additional larger studies are needed to confirm our results.

Acute Unilateral Blindness from Superior Ophthalmic Vein Thrombosis: A Rare Presentation of Nephrotic Syndrome from Class IV Lupus Nephritis in the Absence of Antiphospholipid or Anticardiolipin Syndrome.

Patients with systemic lupus erythematosus (SLE) are at high risk of arterial and venous thrombosis secondary to anti-phospholipid antibodies. Herein, we are presenting an interesting case of venous thrombosis in a patient with SLE in the absence of anti-phospholipid antibodies.