Publications

2017

Kharfan-Dabaja, Mohamed A, Monzr M Al Malki, Uday Deotare, Renju Raj V, Najla El-Jurdi, Navneet Majhail, Mohamad A Cherry, et al. (2017) 2017. “Haematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A North American Multicentre Collaborative Study.”. British Journal of Haematology 179 (5): 781-89. https://doi.org/10.1111/bjh.14954.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is incurable with conventional therapies. Limited retrospective data have shown durable remissions after haematopoietic cell transplantation (HCT) [allogeneic (allo) or autologous (auto)]. We conducted a multicentre retrospective study in BPDCN patients treated with allo-HCT and auto-HCT at 8 centres in the United States and Canada. Primary endpoint was overall survival (OS). The population consisted of 45 consecutive patients who received an allo-HCT (n = 37) or an auto-HCT (n = 8) regardless of age, pre-transplant therapies, or remission status at transplantation. Allo-HCT recipients were younger (50 (14-74) vs. 67 (45-72) years, P = 0·01) and had 1-year and 3-year OS of 68% [95% confidence interval (CI) = 49-81%] and 58% (95% CI = 38-75%), respectively. Allo-HCT in first complete remission (CR1) yielded superior 3-year OS (versus not in CR1) [74% (95% CI = 48-89%) vs. 0, P < 0·0001]. Allo-HCT outcomes were not impacted by regimen intensity [3-year OS for myeloablative conditioning = 61% (95% CI = 28-83%) vs. reduced-intensity conditioning = 55% (95% CI = 28-76%)]. One-year OS for auto-HCT recipients was 11% (95% CI = 8-50%). These results demonstrate efficacy of allo-HCT in BPDCN, especially in patients in CR1. Pertaining to auto-HCT, our results suggest lack of efficacy against BPDCN, but this observation is limited by the small sample size. Larger prospective studies are needed to better define the role of HCT in BPDCN.

Shiani, Ashok, Seth Lipka, Andrew Lai, Andrea C Rodriguez, Christian M Andrade, Ambuj Kumar, and Patrick Brady. (2017) 2017. “Carbon Dioxide versus Room Air Insufflation During Balloon-Assisted Enteroscopy: A Systematic Review With Meta-Analysis.”. Endoscopy International Open 5 (1): E67-E75. https://doi.org/10.1055/s-0042-118702.

Background and study aims Carbon dioxide (CO2) insufflation has been suggested to be an ideal alternative to room air insufflation to reduce trapped air within the bowel lumen after balloon assisted enteroscopy (BAE). We performed a systematic review and meta-analysis to assess the safety and efficacy of utilizing CO2 insufflation as compared to room air during BAE. Patients and methods The primary outcome is mean change in visual analog scale (VAS; 10 cm) at 1, 3, and 6 hours to assess pain. Secondary outcomes include insertion depth (anterograde or retrograde), adverse events, total enteroscopy rate, diagnostic yield, mean anesthetic dosage, and PaCO2 at procedure completion. We searched MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until May 2015. Multiple independent extractions were performed, the process was executed as per the standards of the Cochrane collaboration. Results Four randomized controlled trials (RCTs) were included in the meta-analysis. VAS at 6 hours favored CO2 over room air (MD 0.13; 95 % CI 0.01, 0.25; p = 0.03). Anterograde insertion depth (cm) was improved in the CO2 group (MD, 58.2; 95 % CI 17.17, 99.23; p = 0.005), with an improvement in total enteroscopy rate in the CO2 group (RR 1.91; 95 % CI 1.20, 3.06; p = 0.007). Mean dose of propofol (mg) favored CO2 compared to air (MD, - 70.53; 95 % CI - 115.07, - 25.98; P = 0.002). There were no differences in adverse events in either group. Conclusions Despite the ability of CO2 to improve insertion depth and decrease amount of anesthesia required, further randomized control trials are needed to determine the agent of choice for insufflation in balloon assisted enteroscopy.

Caire, Thure, Ambuj Kumar, Todd Stravitz, and Nyingi Kemmer. (2017) 2017. “Preliver Transplant Red Cell Distribution Width Predicts Postliver Transplant Mortality.”. Clinical Transplantation 31 (3). https://doi.org/10.1111/ctr.12908.

PURPOSE: Prognostication following liver transplantation is limited. Red cell distribution width (RDW) has been associated with morbidity and mortality in a variety of diseases. We hypothesize RDW is predictive of mortality postliver transplantation.

METHODS: We performed a retrospective cohort study of all consecutive liver transplantation recipients at a tertiary care center from January 1, 2012 to December 31, 2012. The primary end point was association of RDW with one-year mortality. Statistical analysis was performed using the Mann-Whitney test, independent samples t test, and regression analysis. Discrimination was assessed by calculating area under receiver operating curves (AUC). A P-value <.05 was considered significant.

RESULTS: RDW was positively associated with one-year mortality (P<.001). The mean difference for survivors compared to nonsurvivors was 3.9% (95% CI 1.9%-5.9%). The AUC for RDW was 0.831 (95% CI 0.727-0.935), compared to 0.723 (0.539-0.908) for total bilirubin and 0.704 (0.479-0.929) for the international normalized ratio.

CONCLUSIONS: To our knowledge, this is the first report of an association of RDW with post-LT mortality and the results show the predictive value of pre-LT RDW for one-year mortality.

Zimmerman, Amanda L, Bugra Tugertimur, Paul D Smith, Ambuj Kumar, and Deniz Dayicioglu. (2017) 2017. “In the Age of Breast Augmentation, Breast Reconstruction Provides an Opportunity to Augment the Breast.”. Cancer Control : Journal of the Moffitt Cancer Center 24 (4): 1073274817729064. https://doi.org/10.1177/1073274817729064.

BACKGROUND: Augmentation mammoplasty remains the most common cosmetic surgery procedure performed. The objective of this article is to evaluate the impact of augmented volume of the reconstructed breast in patients that undergo nipple-sparing mastectomy and patients previously augmented who undergo mastectomy with tissue expander/implant-based reconstruction.

METHODS: Patients undergoing skin-sparing mastectomy, nipple-sparing mastectomy, and mastectomy after previous augmentation followed by tissue expander/implant-based reconstruction between June 2011 and April 2015 by 2 surgeons at the same institution were included. Retrospective chart review of the patients identified using these criteria was performed to record patient characteristics, complications, breast volume, implant volume, and percentage change in volume at the time of reconstruction. Percentage change of breast volume was calculated using the formula (implant breast weight)/(breast weight) for skin-sparing and nipple-sparing mastectomy patients and (final breast implant weight - [breast weight + augmentation breast implant weight])/([breast weight + augmentation breast implant]) for patients undergoing mastectomy following previous augmentation.

RESULTS: A total of 293 patients were included in the study with 63 patients who underwent nipple-sparing mastectomy, 166 patients who underwent skin-sparing mastectomy, and 64 patients who underwent previous augmentation with subsequent mastectomy. Mean percentage change in breast volume was 66% in the nipple-sparing mastectomy group, 15% for the right breast and 18% for the left breast in the skin-sparing mastectomy group, and 81% for the right breast and 72% for the left breast in the mastectomy following previous augmentation group. Complication rate for nipple-sparing mastectomy was 27%, mastectomy following previous augmentation was 20.3%, and skin-sparing mastectomy group was 18.7%.

CONCLUSION: Patients who undergo nipple-sparing mastectomy or mastectomy following previous augmentation have the ability to achieve greater volume in their reconstructed breast via tissue expander/implant-based reconstruction.

Andrade, Christian M, Brijesh Patel, Meghana Vellanki, Ambuj Kumar, and Gitanjali Vidyarthi. (2017) 2017. “Safety of Gastrointestinal Endoscopy With Conscious Sedation in Obstructive Sleep Apnea.”. World Journal of Gastrointestinal Endoscopy 9 (11): 552-57. https://doi.org/10.4253/wjge.v9.i11.552.

AIM: To perform a systematic review and meta-analysis to assess the safety of conscious sedation in patients with obstructive sleep apnea (OSA).

METHODS: A comprehensive electronic search of MEDLINE and EMBASE was performed from inception until March 1, 2015. In an effort to include unpublished data, abstracts from prior gastroenterological society meetings as well as other reference sources were interrogated. After study selection, two authors utilizing a standardized data extraction form collected the data independently. Any disagreements between authors were resolved by consensus among four authors. The methodological quality was assessed using the Newcastle Ottawa tool for observational studies. The primary variables of interest included incidence of hypoxia, hypotension, tachycardia, and bradycardia. Continuous data were summarized as odds ratio (OR) and 95%CI and pooled using generic inverse variance under the random-effects model. Heterogeneity between pooled studies was assessed using the I2 statistic.

RESULTS: Initial search of MEDLINE and EMBASE identified 357 citations. A search of meeting abstracts did not yield any relevant citations. After systematic review and exclusion consensus meetings, seven studies met the a priori determined inclusion criteria. The overall methodological quality of included studies ranged from moderate to low. No significant differences between OSA patients and controls were identified among any of the study variables: Incidence of hypoxia (7 studies, 3005 patients; OR = 1.11; 95%CI: 0.73-1.11; P = 0.47; I2 = 0%), incidence of hypotension (4 studies, 2125 patients; OR = 1.10; 95%CI: 0.75-1.60; P = 0.63; I2 = 0%), incidence of tachycardia (3 studies, 2030 patients; OR = 0.94; 95%CI: 0.53-1.65; P = 0.28; I2 = 21%), and incidence of bradycardia (3 studies, 2030 patients; OR = 0.88; 95%CI: 0.63-1.22; P = 0.59; I2 = 0%).

CONCLUSION: OSA is not a significant risk factor for cardiopulmonary complications in patients undergoing endoscopic procedures with conscious sedation.

Kuykendall, Lauren, V, Bugra Tugertimur, Corin Agoris, Sara Bijan, Ambuj Kumar, and Deniz Dayicioglu. (2017) 2017. “Unilateral Versus Bilateral Breast Reconstruction: Is Less Really More?”. Annals of Plastic Surgery 78 (6S Suppl 5): S275-S278. https://doi.org/10.1097/SAP.0000000000001030.

OBJECTIVE: Over the recent years, there has been an increase in prophylactic mastectomies with an associated increase in bilateral breast reconstruction. We aimed to compare outcomes in terms of patient satisfaction with unilateral versus bilateral breast reconstruction after deep inferior epigastric perforator (DIEP) flap and implant-based reconstruction.

METHODS: Patients who underwent breast reconstruction by a single surgeon between July 2011 and July 2015 were surveyed using the independently validated BREAST-Q questionnaire. Mean satisfaction scores between patients undergoing unilateral versus bilateral breast reconstruction were compared and stratified based on the type of reconstruction [eg, DIEP flap, tissue expander to implant (TE/I)]. Groups were further categorized by age (patients <55 years and ≥55 years of age) and body mass index (<24.9 and >24.9). Complications were recorded.

RESULTS: Of the 308 patients included, 118 (38%) had unilateral reconstruction (42 TE/I and 76 DIEP) and 190 (62%) had bilateral reconstruction (124 TE/I and 66 DIEP). A total of 95 patient surveys were included (31% response rate). Overall, patients receiving unilateral reconstruction demonstrated increased satisfaction with outcome (P = 0.028), psychosocial well-being (P = 0.043), and sexual well-being (P = 0.002). Complication rates were similar between unilateral and bilateral reconstruction. No significant differences for satisfaction were found in the TE/I group (N = 58; unilateral, 10; bilateral, 48).In the DIEP group (N = 37; unilateral, 20; bilateral, 17), those receiving unilateral reconstruction had higher satisfaction with outcome (P = 0.013) and sexual well-being (P = 0.014).Additionally, younger patients (<55 years) were more likely to undergo bilateral reconstruction (P = 0.018). Body mass index did not have a significant association with unilateral or bilateral reconstruction.

CONCLUSIONS: Patients undergoing DIEP flap reconstruction showed higher satisfaction with unilateral reconstruction, whereas patients receiving TE/I reconstruction, either unilateral or bilateral, were equally satisified. Additionally, younger women were more likely to undergo bilateral reconstruction, which is consistent with current data trends. When considering surgical options, unilateral DIEP flap reconstruction may provide improved outcomes in terms of patient satisfaction when compared with bilateral reconstruction in select patients.

Elston, Joshua B, Sangeetha Prabhakaran, Amina Lleshi, Brianna Castillo, Weihong Sun, Ambuj Kumar, Zhenjun Ma, Paul D Smith, and Deniz Dayicioglu. (2017) 2017. “Complications and Recurrence in Implant-Sparing Oncologic Breast Surgery.”. Annals of Plastic Surgery 78 (6S Suppl 5): S269-S274. https://doi.org/10.1097/SAP.0000000000001039.

BACKGROUND: Patients with a history of prior breast augmentation and newly diagnosed breast cancer represent a rapidly expanding and unique subset of patients. Prior studies have described changes in breast parenchyma and characteristic body habitus of previously augmented patients, as well as increased rates of capsular contracture associated with breast conservation therapy. In our current study, we aimed to study the risk factors contributing to morbidity and whether recurrence rates are higher in patients with prior breast augmentation undergoing lumpectomy or mastectomy for breast cancer and identify differences in complications between these 2 groups.

METHODS: Retrospective analysis approved by institutional review board was performed on patients with prior breast augmentation undergoing lumpectomy (N = 52) and mastectomy (N = 64) for breast cancer.

RESULTS: Patients with prior breast augmentation undergoing mastectomy had a higher rate of complications compared with those undergoing lumpectomy (20.3% vs 5.9% respectively, P = 0.031), after adjusting for patient-specific factors including body mass index [odds ratio (OR), 0.242; 95% confidence interval (CI), 0.063-0.922; P = 0.0376], tumor stage (OR, 0.257; 95% CI, 0.064-1.036; P = 0.0562), smoking status (OR, 0.244; 95% CI, 0.065-0.918; P = 0.0370), and chemotherapy (OR, 0.242; 95% CI, 0.064-0.914; P = 0.0364). Four patients (7.7%) developed late complications in the lumpectomy group with 2 developing capsular contractures, 1 had fat necrosis and 1 needed complex reconstruction because of flattening of the nipple-areolar complex. There was no difference in recurrence or tumor margins between lumpectomy and mastectomy groups.

CONCLUSIONS: Patients with prior breast augmentation undergoing mastectomy have higher complication rates compared with lumpectomy even after adjusting for tumor stage. There appears to be no increased oncologic risk associated with either procedure given our current follow-up. Understanding these operative risks may help in patients' decision-making process with regards to type of oncologic surgery.

Buttermore, Stephanie T, Mitchel S Hoffman, Ambuj Kumar, Anne Champeaux, Santo Nicosia V, and Patricia A Kruk. (2017) 2017. “Increased RHAMM Expression Relates to Ovarian Cancer Progression.”. Journal of Ovarian Research 10 (1): 66. https://doi.org/10.1186/s13048-017-0360-1.

BACKGROUND: Elevated hyaluronan-mediated motility receptor (RHAMM) has been reported to contribute to disease progression, aggressive phenotype and poor prognosis in multiple cancer types, however, RHAMM's role in ovarian cancer (OC) has not been elucidated. Therefore, we sought to evaluate the role for RHAMM in epithelial OC.

RESULTS: Despite little to no expression in normal ovarian surface epithelium, western immunoblotting, immunohistochemical staining and enzyme linked immunosorbent assay showed elevated RHAMM levels in clinical tissue sections, omental metastasis and urine specimens of serous OC patients, as well as in cell lysates. We also found that RHAMM levels increase with increasing grade and stage in serous OC tissues and that RHAMM localizes to the apical cell surface and inclusion cysts. Apical localization of RHAMM suggested protein secretion which was validated by detection of significantly elevated urinary RHAMM levels (p < 0.0001) in OC patients (116.66 pg/mL) compared with normal controls (8.16 pg/mL). Likewise, urinary RHAMM levels decreased following cytoreductive surgery in OC patients suggesting the source of urinary RHAMM from tumor tissue. Lastly, we validated RHAMM levels in OC cell lysate and found at least 12× greater levels compared to normal ovarian surface epithelial cells.

CONCLUSION: This pilot study shows, for the first time, that RHAMM may contribute to OC disease and could potentially be used as a prognostic marker.

Reljic, Tea, Ambuj Kumar, Farina A Klocksieben, and Benjamin Djulbegovic. (2017) 2017. “Treatment Targeted at Underlying Disease versus Palliative Care in Terminally Ill Patients: A Systematic Review.”. BMJ Open 7 (1): e014661. https://doi.org/10.1136/bmjopen-2016-014661.

OBJECTIVE: To assess the efficacy of active treatment targeted at underlying disease (TTD)/potentially curative treatments versus palliative care (PC) in improving overall survival (OS) in terminally ill patients.

DESIGN: We performed a systematic review and meta-analysis of randomised controlled trials (RCT). Methodological quality of included RCTs was assessed using the Cochrane risk of bias tool.

DATA SOURCES: Medline and Cochrane databases were searched, with no language restriction, from inception to 19 October 2016.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any RCT assessing the efficacy of any active TTD versus PC in adult patients with terminal illness with a prognosis of <6-month survival were eligible for inclusion.

RESULTS: Initial search identified 8252 citations of which 10 RCTs (15 comparisons, 1549 patients) met inclusion criteria. All RCTs included patients with cancer. OS was reported in 7 RCTs (8 comparisons, 1158 patients). The pooled results showed no statistically significant difference in OS between TTD and PC (HR (95% CI) 0.85 (0.71 to 1.02)). The heterogeneity between pooled studies was high (I2=62.1%). Overall rates of adverse events were higher in the TTD arm.

CONCLUSIONS: Our systematic review of available RCTs in patients with terminal illness due to cancer shows that TTD compared with PC did not demonstrably impact OS and is associated with increased toxicity. The results provide assurance to physicians, patients and family that the patients' survival will not be compromised by referral to hospice with focus on PC.