Somashekar G. Krishna

Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4–6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080–2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065–2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease

Complete response (CR) is still considered an important surrogate marker for outcome in multiple myeloma (MM). Long‐term survival after transplantation, however, has been observed in a substantial proportion of patients who never achieved CR. The tandem transplant trial, Total Therapy 2, enrolled 668 patients, who were randomised up‐front to thalidomide (THAL) or no THAL; 56 patients were identified as having had, for at least 6 months prior to initiation of therapy, monoclonal gammopathy of undetermined significance (MGUS, n = 21), smouldering MM (SMM, n = 22) or solitary plasmacytoma of bone (SPC, n = 13). The clinical characteristics and outcomes of patients with such ‘evolved’ MM (E‐MM) and of those with ‘unknown’ prior history (U‐MM) were compared. Fewer patients with MGUS/SMM‐E‐MM had anaemia or renal failure; CR was lower (22% vs. 48%) but 4‐year estimates of event‐free survival (54% vs. 56% with U‐MM) and overall survival (65% vs. 70% with U‐MM) were similar to those with SPC‐E‐MM or U‐MM. In the latter group, achieving CR was associated with prolonged survival. In comparison with U‐MM, E‐MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting survival. In contrast, CR was an independent favourable feature for survival in U‐MM.

Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT

BACKGROUND Diagnosis of pancreatic neoplasm is challenging in patients with inconclusive findings on pancreatic multidetector row CT (MDCT). OBJECTIVE To determine the diagnostic accuracy and to identify predictors of pancreatic neoplasm by EUS with FNA in this setting. DESIGN Retrospective chart review during the study period of January 2002 to December 2010. SETTING Tertiary referral center. PATIENTS Of the 1046 patients who underwent pancreatic EUS, 116 patients were selected because their clinical presentation was suspicious for pancreatic malignancy, but their MDCT findings were inconclusive. INTERVENTION EUS with FNA. MAIN OUTCOME MEASUREMENTS Diagnostic yield of malignancy and significance of clinical variables. RESULTS When surgical pathology or subsequent clinical course was used as the criterion standard, EUS with FNA had a sensitivity, specificity, positive predictive value, and accuracy of 87.3%, 98.3%, 98.5%, and 92.1%, respectively, in diagnosing a pancreatic neoplasm that was indeterminate on MDCT. Factors significantly associated with EUS detection of pancreatic ductal adenocarcinoma were total bilirubin level greater than 2 mg/dL (P < .001), CT finding of pancreatic duct dilation (P < .001), bile duct stricture (P < .001), and tumor size 1.5 cm or larger detected by EUS (P = .004). Among them, pancreatic duct dilation on CT (odds ratio 4.10; 95% confidence interval, 1.52-11.05), and tumor size 1.5 cm or larger detected by EUS (odds ratio 8.46; 95% confidence interval, 2.02-35.45) were independent risk factors. LIMITATIONS Retrospective design and patient referral bias. CONCLUSIONS When MDCT is indeterminate, EUS is a highly sensitive and accurate modality for the detection of pancreatic neoplasm, especially when the tumor is smaller than 2.0 cm.

Morbid Obesity Is Associated With Adverse Clinical Outcomes in Acute Pancreatitis: A Propensity-Matched Study.

OBJECTIVES:Morbid obesity may adversely affect the clinical course of acute pancreatitis (AP); however, there are no inpatient, population-based studies assessing the impact of morbid obesity on AP-related outcomes. We sought to evaluate the impact of morbid obesity on AP-related clinical outcomes and health-care utilization.METHODS:The Nationwide Inpatient Sample (2007–2011) was reviewed to identify all adult inpatients (≥18 years) with a principal diagnosis of AP. The primary clinical outcomes (mortality, renal failure, and respiratory failure) and secondary resource outcomes (length of stay and hospital charges) were analyzed using univariate and multivariate comparisons. Propensity score-matched analysis was performed to compare the outcomes in patients with and without morbid obesity.RESULTS:Morbid obesity was associated with 3.9% (52,297/1,330,302) of all AP admissions. Whereas the mortality rate decreased overall (0.97%0.83%, P<0.001), it remained unchanged in those with morbid obesity (1.02%1.07%, P=1.0). Multivariate analysis revealed that morbid obesity was associated with increased mortality (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.3, 1.9), prolonged hospitalization (0.4 days; P<0.001), and higher hospitalization charges (

Adenoma detection in patients undergoing a comprehensive colonoscopy screening

5,067; P<0.001). A propensity score-matched cohort analysis demonstrated that the primary outcomes, acute kidney failure (10.8 vs. 8.2%; P<0.001), respiratory failure (7.9 vs. 6.4%; P<0.001), and mortality (OR 1.6, 95% CI 1.2, 2.1) were more frequent in morbid obesity.CONCLUSIONS:Morbid obesity negatively influences inpatient hospitalization and is associated with adverse clinical outcomes, including mortality, organ failure, and health-care resource utilization. These observations and the increasing global prevalence of obesity justify ongoing efforts to understand the role of obesity-induced inflammation in the pathogenesis and management of AP.

Incidence and Risk Factors for Lower Alimentary Tract Mucositis After 1529 Courses of Chemotherapy in a Homogenous Population of Oncology Patients: Clinical and Research Implications

Measures shown to improve the adenoma detection during colonoscopy (excellent bowel preparation, cecal intubation, cap fitted colonoscope to examine behind folds, patient position change to optimize colon distention, trained endoscopy team focusing on detection of subtle flat lesions, and incorporation of optimum endoscopic examination with adequate withdrawal time) are applicable to clinical practice and, if incorporated are projected to facilitate comprehensive colonoscopy screening program for colon cancer prevention. To determine adenoma and serrated polyp detection rate under conditions designed to optimize quality parameters for comprehensive screening colonoscopy. Retrospective analysis of data obtained from a comprehensive colon cancer screening program designed to optimize quality parameters. Academic medical center. Three hundred and forty‐three patients between the ages of 50 years and 75 years who underwent first screening colonoscopy between 2009 and 2011 among 535 consecutive patients undergoing colonoscopy. Comprehensive colonoscopy screening program was utilized to screen all patients. Cecal intubation was successful in 98.8% of patients. The Boston Bowel Preparation Scale for quality of colonoscopy was 8.97 (95% confidence interval [CI]; 8.94, 9.00). The rate of adenoma detection was 60% and serrated lesion (defined as serrated adenomas or hyperplastic polyps proximal to the splenic flexure) detection was 23%. The rate of precancerous lesion detection (adenomas and serrated lesions) was 66%. The mean number of adenomas per screening procedure was 1.4 (1.2, 1.6) and the mean number of precancerous lesions (adenomas or serrated lesions) per screening procedure was 1.6 (1.4, 1.8). Retrospective study and single endoscopist experience. A comprehensive colonoscopy screening program results in high‐quality screening with high detection of adenomas, advanced adenomas, serrated adenomas, and multiple adenomas.

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

Lower alimentary tract mucositis is a serious complication of chemotherapy. The aim of the study was to determine the incidence, risk factors, and mortality of lower alimentary tract mucositis in a homogeneous population of patients with newly diagnosed myeloma receiving similar antineoplastic therapy and standardized supportive care.

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions

The duration of neutropenia (absolute neutrophil count (ANC) ⩽100/μl) identifies cancer patients at risk for infection. A test that precedes ANC⩾100/μl would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANC⩾100/μl in 99% of patients after the first Mel-ASCT by (mean±s.d.) 4.23±1.96 days and in 97% of the patients after the second Mel-ASCT by 4.11±1.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte count⩾100/μl to the time to ANC⩾100/μl. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC⩾100/μl.

Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium difficile infection in cancer patients

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss’ kappa) and IOR (Cohen’s kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was “substantial” (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was “substantial” (κ = 0.78 ± 0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were “substantial” for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ± 0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ± 0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ± 0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events. Study registration: NCT02516488

Intrapancreatic Accessory Spleen: Investigative Dilemmas and Role of EUS-Guided FNA for Diagnostic Confirmation

Clostridium difficile infection (CDI) is a serious complication of chemotherapy including high‐dose regimens with autologous stem cell transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and preemptive CDI therapy is not recommended. We assessed the incidence, risk factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma (MM) receiving similar antineoplastic therapy and supportive care including antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea.