Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma: a single-institution experience.

Extranodal marginal zone lymphoma (EMZL) encompasses 70% of cases of marginal zone lymphoma. Frontline bendamustine and rituximab (BR) were derived from trials involving other indolent non-Hodgkin's lymphomas. Only one trial has evaluated frontline BR prospectively in EMZL. This retrospective study reports outcomes among EMZL patients receiving frontline BR. Twenty-five patients were included with a median age of 69 years (40-81). Five (20.0%) patients had stage I/II disease, and 20 (80.0%) had stage III/IV disease. The median number of cycles was 6.0 (3.0-6.0). Maintenance rituximab was administered to 10 (41.7%) individuals. Overall response rate (ORR) was 100.0% (60.0% complete response, 40.0% partial response). Medians of overall survival and progression-free survival were not reached. The estimated 2-year progression-free survival was 85.2% and overall survival was 100.0%. Four (16.6%) patients had infections related to treatment; 3 (12.0%) transformed to diffuse large B-cell lymphoma; 5 (20.8%) had a relapse or progression of EMZL; and 3 (12.0%) died unrelated to BR. BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality.

PURPOSE: Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have shown CD83 chimeric antigen receptor (CAR) T cells prevent GVHD and kill myeloid leukemia cell lines. In this pilot study, we investigate CD83 expression on GVHD effector cells, correlate these discoveries with clinical outcomes, and evaluate critical therapeutic implications for transplant recipients. EXPERIMENTAL DESIGN: CD83 expression was evaluated among circulating CD4+ T cells, B-cell subsets, T follicular helper (Tfh) cells, and monocytes from patients with/without acute or chronic GVHD (n = 48 for each group), respectively. CD83 expression was correlated with survival, TRM, and relapse after alloHCT. Differential effects of GVHD therapies on CD83 expression was determined. RESULTS: CD83 overexpression on CD4+ T cells correlates with reduced survival and increased TRM. Increased CD83+ B cells and Tfh cells, but not monocytes, are associated with poor posttransplant survival. CD83 CAR T eliminate autoreactive CD83+ B cells isolated from patients with chronic GVHD, without B-cell aplasia as observed with CD19 CAR T. We demonstrate robust CD83 antigen density on human acute myeloid leukemia (AML), and confirm potent antileukemic activity of CD83 CAR T in vivo, without observed myeloablation. CONCLUSIONS: CD83 is a promising diagnostic marker of GVHD and warrants further investigation as a therapeutic target of both GVHD and AML relapse after alloHCT.

Standardization of the Discharge Process for Inpatient Hematology and Oncology Using Plan-Do-Study-Act Methodology Improves Follow-Up and Patient Hand-Off.

BACKGROUND: Hematology and oncology patients represent a complex population that requires timely follow-up to prevent clinical decompensation and delays in treatment. Previous reports have demonstrated that follow-up within 14 days is associated with decreased 30-day readmissions, and the magnitude of this effect is greater for higher-risk patients. This project was designed to standardize the discharge process with the primary goal of reducing average time to hematology and oncology follow-up to < 14 days. METHODS: Using Plan-Do-Study-Act (PDSA) quality improvement methodology, a multidisciplinary team of hematology and oncology staff developed and implemented a standardized discharge process. Rotating resident physicians were trained through online and in-person education. Additional interventions included the development of a discharge checklist handout, and a clinical decision support tool including a note template and embedded order set. All patients discharged during the 2-month period before and after the implementation of the standardized process were evaluated. Follow-up appointment scheduling data and communication between inpatient and outpatient providers were reviewed. RESULTS: A total of 142 consecutive patients were reviewed. The primary endpoint of time to hematology and oncology follow-up appointment improved from a mean 17 days prior to intervention to 13 days in PDSA cycles 1 and 2 and 10 days in PDSA cycle 3. The target of 14-day average time to follow-up was achieved. Furthermore, the upper control limit decreased from 58 days at baseline to 21 days in PDSA cycle 3, demonstrating a decrease in variation. Electronic alerting of outpatient hematology and oncology providers to discharge summary increased from 20% before the intervention to 62% after the intervention (P = .01). CONCLUSIONS: This quality initiative to standardize the discharge process for the hematology and oncology service decreased time to hematology and oncology follow-up appointments, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population will prevent clinical decompensation and delays in treatment.

Impact of Pharmacist-Psychiatrist Collaborative Patient Education on Medication Adherence and Quality of Life (QOL) of Bipolar Affective Disorder (BPAD) Patients.

Background: Bipolar Affective Disorder (BPAD) is one of the leading causes of disability globally. Medication non-adherence and low quality of life (QOL) are the major challenges associated with the treatment of BPAD patients. Objective: Aim of this study was to assess the impact of pharmacist-psychiatrist collaborative patient education on medication adherence and QOL of BPAD patients. Methodology: A prospective randomized control study was conducted in the psychiatry outpatient department in a tertiary care setting. The eligible patients were enrolled and randomized into test (collaborative care) and control (usual care) groups. Patient education was provided by pharmacists to the test group patients, along with the usual care provided to all the patients. Patients were followed for three follow-ups of nearly 1 month intervals. Medication adherence and QOL were assessed by Medication Adherence Rating Scale and WHOQOL-BREF questionnaire, respectively. T-test was used and P-values < 0.05 were considered statistically significant. Results: Out of 75 patients enrolled, 73 patients were followed for all the three follow-ups and completed the study. Thirty-eight patients belonged to test and 35 were in control group. The mean age of patients was 34.21 ± 10.91 years. Forty-eight (65.75%) patients belonged to age group of 18-39 years. There were 41 males (56.16%) and 32 female patients (43.83%) in the study. Mean improvement in medication adherence and QOL of the test and control groups were found to be 2.06 ± 0.15 (<0.001) and 13.8 ± 10.5 (<0.05), respectively. Conclusion: This study concluded that pharmacist-psychiatrist collaborative patient education can significantly improve the medication adherence and QOL of the BPAD patients. Statistically significant results indicating improved patient care and outcomes were possible when pharmacists worked as a team with psychiatrists.

Predictors of Postoperative Complications in Patients Who Undergo Radical Nephrectomy and IVC Thrombectomy: A Large Contemporary Tertiary Center Analysis.

UNLABELLED: In an analysis of a large single-institution experience in the surgical management of renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus, the authors present the effect of RCC characteristics on survival, and aim to identify potential preoperative variables predictive of intraoperative complexity with regard to estimated blood loss, transfusion volume, surgical time, length of stay, and postoperative complication rates. Age, American Society of Anesthesiologists score, Charlson Comorbidity Index, preoperative calcium, preoperative creatinine, and IVC wall invasion were significantly related to complication rates. INTRODUCTION: Preoperative laboratory values are commonly used as markers of health and potential disease burden, however, their effect on perioperative complexity has not previously been assessed. The authors aimed to evaluate the effect of renal cell carcinoma and inferior vena cava (IVC) thrombus characteristics on cancer-specific survival (CSS), and identify potential preoperative variables predictive of intraoperative complexity. MATERIALS AND METHODS: In a retrospective chart review we identified 144 patients who underwent nephrectomy and IVC thrombectomy. Univariate and multivariate analyses were used to assess the effect of disease characteristics on CSS and postoperative complications. Linear regression analysis was used to determine the association between preoperative laboratory values and intraoperative complexity characterized by estimated blood loss (EBL), transfusion volume (TV), operative time, and length of hospital stay (LOS). RESULTS: Analysis of intraoperative complexity revealed a significant correlation between preoperative creatinine (Cr) and EBL (P = .022), TV (P = .041), and LOS (P = .005), and preoperative hemoglobin (Hgb) was associated with increased EBL (P < .001) and TV (P < .001). Multivariate analyses showed a significant relationship between overall complication rates and preoperative calcium (Ca; P = .012), American Society of Anesthesiologists (ASA) score (P = .003), and IVC wall invasion (P = .005), and a significant association between major complications and preoperative Ca (P = .011), preoperative Cr (P = .041), age (P = .050), and Charlson Comorbidity Index (CCI; P = .002). CONCLUSION: With regard to intraoperative complexity and postoperative complications, preoperative Cr and Hgb were significantly associated with increased EBL, TV, and LOS, and ASA score, preoperative Ca, preoperative Cr, IVC wall invasion, age, and CCI were found to have significant relationships with complication rates.

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy.

PURPOSE: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. MATERIALS AND METHODS: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. RESULTS: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. CONCLUSION: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy

ABSTRACT Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. Results: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. Conclusion: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.

Caval tumor thrombus volume influences outcomes in renal cell carcinoma with venous extension.

INTRODUCTION: Surgery for renal cell carcinoma with tumor thrombus has a high potential morbidity rate, and the current classification system based on proximal tumor thrombus level (TTL) has not been shown to consistently predict outcomes. AIM: To assess the prognostic value of inferior vena cava tumor thrombus volume (IVC-TV) for determining the perioperative complications as well as with survival end points. METHODS: From June 2001 to June 2012, we identified 147 patients who underwent radical nephrectomy with venous thrombi. In total, 66 patients had IVC involvement and available imaging for review. IVC-TV was measured by cross-sectional area and height measurement for each axial slice. Linear, logistic models and Cox proportional hazard was used for analysis. RESULTS: Median IVC-TV was 16.5 cm(3), and 18 patients had TTL≥III. In total, 57 Clavien I-V complications were documented in 32 patients including 3 deaths. On multivariate analysis, age>65 years, American Society of Anesthesiologists>3, and IVC-TV>15 cm(3) were independent predictors for perioperative complications. Disease progression (PoD) occurred in 78% of patients, and metastatic disease (hazard ratio [HR] = 3.33, P<0.01) and non-clear cell histology (HR = 2.98, P = 0.02) were independent predictors of PoD. Median time to death was 16 months (interquartile range: 5.2-42.9). On Cox regression analysis, metastatic disease, non-clear cell histology, IVC-TV>15 cm(3), and TTL III/IV were significantly associated with overall survival. As a preoperative variable, IVC-TV>15 cm(3) was shown to be an independent predictor of PoD (HR = 2.3, P = 0.01) and overall survival (HR = 2.21, P = 0.03). CONCLUSION: IVC-TV has value as a prognostic indicator, which is superior to TTL in the setting of renal cell carcinoma with IVC venous thrombus.

Margin status impacts survival after pancreaticoduodenectomy but negative margins should not be pursued.

Negative margins are the goal with pancreaticoduodenectomy for pancreatic adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen section analysis and negative margins are pursued. This study was undertaken to determine the impact of margin status with pancreaticoduodenectomy for pancreatic adenocarcinoma and the value of extending resections to achieve negative margins. The intraoperative frozen section analysis and final margins for 448 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed and their impact on survival was determined. Median data are presented. Two hundred ninety-eight (67%) patients had negative margins (R0), an additional 110 (25%) patients had microscopically positive and macroscopically negative margins (R1), and an additional 40 (9%) patients had initially positive microscopic margins, which became negative with further resection (R1 → R0). R0 resections were more likely to have smaller tumors, earlier T grade, earlier N grade, lower American Joint Committee on Cancer stage, and less frequent extrapancreatic extension (P ≤ 0.03 for each). Survival was better with R0 resections than R1 resections (20 vs 12 months, P < 0.001); extending resections to achieve negative margins (i.e., R1 → R0) did not improve survival beyond R1 resections (14 vs 12 months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing. Patients with initial negative margins do best. Positive microscopic margins reflect more aggressive tumor-specific factors and lead to abbreviated survival even with extended resections to achieve negative margins (i.e., R1 → R0). With an initial positive margin, pursuing negative margins does not improve survival and, thereby, negative margins should not be "chased."

Defining the learning curve of laparoendoscopic single-site Heller myotomy.

Initial outcomes suggest laparoendoscopic single-site (LESS) Heller myotomy with anterior fundoplication provides safe, efficacious, and cosmetically superior outcomes relative to conventional laparoscopy. This study was undertaken to define the learning curve of LESS Heller myotomy with anterior fundoplication. One hundred patients underwent LESS Heller myotomy with anterior fundoplication. Symptom frequency and severity were scored using a Likert scale (0 = never/not bothersome to 10 = always/very bothersome). Symptom resolution, additional trocars, and complications were compared among patient quartiles. Median data are presented. Preoperative frequency/severity scores were: dysphagia = 10/8 and regurgitation = 8/7. Additional trocars were placed in 12 patients (10%), of whom all were in the first two quartiles. Esophagotomy/gastrotomy occurred in three patients. Postoperative complications occurred in 9 per cent. No conversions to "open" operations occurred. Length of stay was 1 day. Postoperative frequency/severity scores were: dysphagia = 2/0 and regurgitation = 0/0; scores were less than before myotomy (P < 0.001). There were no apparent scars, except where additional trocars were placed. LESS Heller myotomy with anterior fundoplication well palliates symptoms of achalasia with no apparent scar. Placement of additional trocars only occurred early in the experience. For surgeons proficient with the conventional laparoscopic approach, the learning curve of LESS Heller myotomy with anterior fundoplication is short and safe, because proficiency is quickly attained.

Important surgical considerations in the management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus.

UNLABELLED: What's known on the subject? and What does the study add? Historically, the surgical management of renal tumours with intravascular tumour thrombus has been associated with high morbidity and mortality. In addition, few cases are treated, and typically at tertiary care referral centres, hence little is known and published about the ideal surgical management of such complex cases. The present comprehensive review details how a multidisciplinary surgical approach to renal tumours with intravascular tumour thrombus can optimise patient outcomes. Similarly, we have developed a treatment algorithm in this review that can be used in the surgical planning of such cases. OBJECTIVES: To detail the perioperative and technical considerations essential to the surgical management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus, as historically patients with RCC and IVC tumour thrombus have had an adverse clinical outcome. • Recent surgical and perioperative advances have for the most part optimized the clinical outcome of such patients. MATERIALS AND METHODS: A comprehensive review of the scientific literature was conducted using MEDLINE from 1990 to present using as the keywords 'renal cell carcinoma' and 'IVC tumor thrombus'. • In all, 62 manuscripts were reviewed, 58 of which were in English. Of these, 25 peer-reviewed articles were deemed of scientific merit and were assessed in detail as part of this comprehensive review. • These articles consist of medium to large (≥25 patients) peer-reviewed studies containing contemporary data pertaining to the surgical management of RCC and IVC tumour thrombus. • Many of these studies highlight important surgical techniques and considerations in the management of such patients and report on their respective clinical outcomes. RESULTS: Careful preoperative planning is essential to optimising the outcomes within this patient cohort. High quality and detailed preoperative imaging studies help delineate the proximal extension of the IVC tumour thrombus and possible caval wall direct invasion while determining the potential necessity for intraoperative vascular bypass. • The surgical management of RCC and IVC tumour thrombus (particularly for level III or IV) often requires the commitment of a multidisciplinary surgical team to optimise patient surgical outcomes. • Despite significant improvements in surgical techniques and perioperative care, the 5-year overall survival remains only between 32% and 69%, highlighting the adverse prognosis of such locally advanced tumours. • Important prognostic factors within this patient cohort include pathological stage, nuclear grade, tumour histology, lymph node and distant metastatic status, preoperative performance status, Charlson comorbidity index, and nutritional status. CONCLUSIONS: The multidisciplinary surgical care of RCC and IVC tumour thrombus (particularly high level thrombi) is pivotal to optimising the surgical outcome of such patients. • Similarly, important preoperative, perioperative, and postoperative considerations can improve the surgical outcome of patients.

Preoperative metastatic status, level of thrombus and body mass index predict overall survival in patients undergoing nephrectomy and inferior vena cava thrombectomy.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known about the prognostic impact of body mass index (BMI) and obesity on patients with locally advanced kidney cancer. Previous studies suggest that clinical/pathological stage, the proximal extent of the tumour thrombus, direct vascular wall invasion, and preoperative performance status may all constitute important prognostic factors within this patient population. The present study shows that a patient's metastatic status, higher level of tumour thrombus, and lower BMI all constitute adverse predictors of overall survival in patients who have RCC with inferior vena cava tumour thrombus. OBJECTIVE: • To determine which clinical variables, including body mass index (BMI), predict overall survival (OS) after nephrectomy with inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC) with tumour thrombus. PATIENTS AND METHODS: • After institutional review board approval, a retrospective analysis of all patients (N= 100) undergoing nephrectomy and IVC thrombectomy for RCC from 1989 to 2010 were reviewed. One patient was excluded owing to missing clinical information leaving 99 patients in the study cohort. • Patients were placed into one of two subgroups, based on their preoperative BMI (BMI ≤30 kg/m(2) or BMI >30 kg/m(2) ). • Complications, blood loss, level of tumour thrombus, side of tumour and follow-up data were tabulated. RESULTS: • Fifty-six patients had a BMI ≤30 kg/m(2) and 43 patients had a BMI >30 kg/m(2) . Intraoperative complications occurred in 14% of those with BMI >30 kg/m(2) and 5.4% of those with a BMI ≤30 kg/m(2) (P= 0.171). • On multivariate analysis, a higher thrombus level (III/IV vs I/II) and the presence of metastatic disease at time of diagnosis was associated with a worse OS (P= 0.041 and P < 0.001, respectively). • The subgroup with a higher preoperative BMI had a significantly better OS (hazard ratio 0.42; 95% confidence interval 0.22-0.80, P= 0.009). • Similarly, our Kaplan-Meier survival analysis showed an improved OS in the patient cohort with a BMI >30 kg/m(2) (P= 0.016). CONCLUSION: • Important predictors of outcome in patients undergoing nephrectomy with IVC thrombectomy for RCC with tumour thrombus include preoperative BMI, level of IVC tumour thrombus, and metastatic status at time of surgery.