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BACKGROUND - Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.
METHODS - Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.
RESULTS - Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.
CONCLUSIONS - In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.
© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
PURPOSE - Multiple choroidal melanomas arising in the same eye is a very rare entity, usually leading ophthalmologists to entertain other diagnoses. Historically, the only available treatment reported for this rare entity was enucleation. In this study we demonstrate in a series of patients with multiple simultaneous choroidal melanomas that eye salvage is possible using a variety of radiotherapy techniques.
OBSERVATIONS - Both patients presented with two simultaneous choroidal melanomas in one eye. The first patient was only 30 years old and presented with two largely amelanotic tumours with large exudative retinal detachment. Cytology from fine needle aspiration biopsies from both tumours with immunohistochemistry confirmed two separate melanomas. Sequential radioactive iodine plaque brachytherapy led to regression of both tumours. The second, older patient's two tumours both had the typical appearance of choroidal melanoma and he underwent proton beam irradiation to the entire field leading to tumour regression.
CONCLUSIONS - Multiple choroidal melanomas can rarely arise simultaneously in the same eye, and despite their variable appearance, a definitive diagnosis can be aided by cytology and immunohistochemistry in atypical-appearing cases. While all other previously reported cases have necessitated enucleation, we demonstrate that globe salvage is possible using either proton beam irradiation to the entire tumour field, or with sequential radioactive plaque brachytherapy.
© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
OPINION STATEMENT - Despite decades of high-quality research, the treatment of rectal cancer remains a work in progress. The interplay between chemotherapy, radiotherapy, and surgery is under constant rearrangement and refinement. Through this all, the desire to preserve the anal sphincters and quality of life remains at the forefront. In the past decade, standard of care for stage II or III rectal cancers in the USA has been neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection of the rectum. While timing and sequence of the CRT continues to evolve, surgical resection has remained essential in treatment. This stands in contrast to anal cancer, where surgery is reserved purely for salvage. This article describes a treatment strategy that attempts to treat rectal adenocarcinoma with CRT alone, reserving surgery for failure or salvage. Of the studies performed to date, a number are methodologically sound and show promise. However, the body of evidence has yet to reach a size to sway practitioners from the established trinity of chemotherapy, radiotherapy, and surgery. Interestingly, few trials administer post treatment full-dose systemic chemotherapy, which is the standard of care in patients undergoing surgical resection. Better identification of patients that will have complete cure from this approach, combined with long-term outcome data on salvage patients, is necessary for this therapy to be universally embraced.
INTRODUCTION - To determine the time to progression (TTP), response rate (RR), and toxicity for North American patients with relapsed small-cell lung cancer (SCLC) treated with bendamustine in the second- or third-line setting.
METHODS - Patients with relapsed, histologically confirmed SCLC were eligible for enrollment on study. The study population included patients with both chemotherapy-sensitive and chemotherapy-resistant disease treated with up to two prior lines of chemotherapy. Patients were treated with 120 mg/m of bendamustine on days 1 and 2 of a 21-day cycle for up to six cycles. Primary end point was TTP; secondary end points included toxicity, RR, and overall survival.
RESULTS - Fifty-nine patients were accrued, 50 patients met eligibility for enrollment. The median age of patients was 62, and 56% were men. Twenty-nine patients (58%) had chemotherapy-sensitive disease. Median TTP was 4.0 months (95% confidence interval [CI], 3.3-5.4), median overall survival was 4.8 months (95% CI, 3.8-6.3), and the RR was 26% (95% CI, 13.3%-39.5%). Patients with chemosensitive disease had a median TTP of 4.2 months (95% CI, 3.3-6.0) compared with 3.4 months (95% CI, 2.7-∞) for chemotherapy-resistant disease. The RR was 33% (95% CI, 14.2%-51.8%) in patients with chemosensitive disease and 17% (95% CI, 0%-34.4%) in those with chemoresistant disease. The most common grade 3/4 adverse events were fatigue (20%), dyspnea (12%), and anemia (12%).
CONCLUSION - Bendamustine has modest activity in relapsed SCLC similar to other agents evaluated in this patient population.
PURPOSE - Salvage robotic assisted laparoscopic prostatectomy is a treatment option for certain patients with recurrent prostate cancer after primary therapy. Data regarding patient selection, complication rates and cancer outcomes are scarce. We report the largest, single institution series to date, to our knowledge, of salvage robotic assisted laparoscopic prostatectomy.
MATERIALS AND METHODS - We reviewed our database of 4,234 patients treated with robotic assisted laparoscopic prostatectomy at Vanderbilt University and identified 34 men who had surgery after the failure of prior definitive ablative therapy. Each patient had biopsy proven recurrent prostate cancer and no evidence of metastases. The primary outcome measure was biochemical failure.
RESULTS - Median time from primary therapy to salvage robotic assisted laparoscopic prostatectomy was 48.5 months with a median preoperative prostate specific antigen of 3.86 ng/ml. Most patients had Gleason scores of 7 or greater on preoperative biopsy, although 12 (35%) had Gleason 8 or greater disease. After a median followup of 16 months 18% of patients had biochemical failure. The positive margin rate was 26%, of which 33% had biochemical failure after surgery. On univariable analysis there was a significant association between prostate specific antigen doubling time and biochemical failure (HR 0.77, 95% CI 0.60-0.99, p = 0.049) as well as between Gleason score at original diagnosis and biochemical failure (HR 3.49, 95% CI 1.18-10.3, p = 0.023). There were 2 Clavien II-III complications, namely a pulmonary embolism and a rectal laceration. Postoperatively 39% of patients had excellent continence.
CONCLUSIONS - Salvage robotic assisted laparoscopic prostatectomy is safe, with many favorable outcomes compared to open salvage radical prostatectomy series. Advantages include superior visualization of the posterior prostatic plane, modest blood loss, low complication rates and short length of stay.
Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
BACKGROUND - The clinical activity of allosteric inhibitors of mammalian target of rapamycin (mTOR) inhibitors in renal cell carcinoma (RCC) may be limited by upstream activation of phosphatidylinositol 3 (PI3)-kinase/Akt resulting from mTOR1 inhibition. On the basis of this rationale, 2 independent phase 2 trials (Perifosine 228 and 231) were conducted to assess the efficacy and safety of the novel Akt inhibitor perifosine in patients with advanced RCC who had failed on previous vascular endothelial growth factor (VEGF)-targeted therapy.
METHODS - In the Perifosine 228 trial, 24 patients with advanced RCC received oral perifosine (100 mg daily). Perifosine 231 enrolled 2 groups that received daily oral perifosine (100 mg daily): Group A comprised 32 patients who had received no prior mTOR inhibitor, and Group B comprised 18 patients who had received 1 prior mTOR inhibitor.
RESULTS - In the Perifosine 228 trial, 1 patient achieved a partial response (objective response rate, 4%; 95% confidence interval, 0.7%-20%), and 11 patients (46%) had stable disease as their best response. The median progression-free survival was 14.2 weeks (95% confidence interval, 7.7-21.6 weeks). In the Perifosine 231 trial, 5 patients achieved a partial response (objective response rate, 10%; 95% confidence interval, 4.5%-22.2%) and 16 patients (32%) had stable disease as their best response. The median progression-free survival was 14 weeks (95% confidence interval, 12.9, 20.7 weeks). Overall, perifosine was well tolerated, and there were very few grade 3 and 4 events. The most common toxicities included nausea, diarrhea, musculoskeletal pain, and fatigue.
CONCLUSIONS - Although perifosine demonstrated activity in patients with advanced RCC after failure on VEGF-targeted therapy, its activity was not superior to currently available second-line agents. Nonetheless, perifosine may be worthy of further study in RCC in combination with other currently available therapies.
Copyright © 2012 American Cancer Society.
PURPOSE - The purpose of this study was to examine factors associated with the presence of secondary external and internal lymphedema in patients with head-and-neck cancer (HNC).
METHODS AND MATERIALS - The sample included 81 patients ≥3 months after HNC treatment. Physical and endoscopic examinations were conducted to determine if participants had external, internal, and/or combined head-and-neck lymphedema. Logistic regression analysis was used to examine the factors associated with the presence of lymphedema.
RESULTS - The following factors were statistically significantly associated with presence of lymphedema: (1) location of tumor associated with presence of external (P=.009) and combined lymphedema (P=.032); (2) time since end of HNC treatment associated with presence of external (P=.004) and combined lymphedema (P=.005); (3) total dosage of radiation therapy (P=.010) and days of radiation (P=.017) associated with the presence of combined lymphedema; (4) radiation status of surgical bed was associated with the presence of internal lymphedema, including surgery with postoperative radiation (P=.030) and (salvage) surgery in the irradiated field (P=.008); and (5) number of treatment modalities associated with external (P=.002), internal (P=.039), and combined lymphedema (P=.004). No demographic, health behavior-related, or comorbidity factors were associated with the presence of lymphedema in the sample.
CONCLUSIONS - Select tumor and treatment parameters are associated with increased occurrence of lymphedema in patients with HNC. Larger and longitudinal studies are needed to identify adjusted effects and causative risk factors contributing to the development of lymphedema in patients with HNC.
Copyright © 2012 Elsevier Inc. All rights reserved.
Complete pancreatic transection (CPT) in children is managed commonly with distal pancreatectomy (DP). Alternatively, Roux-en-Y distal pancreaticojejunostomy (RYPJ) may be performed to preserve pancreatic tissue. The purpose of this study was to review our experience using either procedure in the management of children sustaining CPT after blunt abdominal trauma. We retrospectively reviewed the records of all children admitted to our institution during the last 15 years who were confirmed at operation to have CPT after blunt mechanisms. Summary statistics of demographic data were performed to describe children receiving either RYPJ or DP. CPT occurred in 28 children: 15 had DP, 10 had RYPJ, and three had cystogastrostomy. RYPJ children, compared with DP, were younger (7.5 vs. 12.3 years, P = 0.039) and sustained more grade IV pancreatic injuries (70% vs. 14%, P = 0.01). DP patients were 5.63 times more likely to tolerate full enteral feeds (P = 0.009). Nevertheless, when controlling for age, injury severity score, and pancreatic injury grade, procedure type did not statistically affect total and postoperative lengths of stay and postoperative complications. In the operative management algorithm of children sustaining CPT, DP may afford an earlier return to full enteral feeds. RYPJ seems otherwise equivalent to DP and preserves significant pancreatic glandular tissue and the spleen.
BACKGROUND - 25-hydroxyvitamin D insufficiency is common in healthy children and adolescents. There have been limited studies of the 25-hydroxyvitamin D status of survivors of pediatric and adolescent acute lymphoblastic leukemia (ALL).
PROCEDURE - In a cohort of 78 ALL survivors (52 chemotherapy-treated and 26 HCT-treated), we determined the prevalence of, and host, treatment and environmental risk factors for 25-hydroxyvitamin D insufficiency and deficiency.
RESULTS - There were no differences in serum 25-hydroxyvitamin D levels between ALL survivors treated with conventional chemotherapy and those treated with HCT (median 26.0 vs 25.5 ng/ml). Fifty-three percent of pediatric ALL survivors were 25-hydroxyvitamin D insufficient (15-29 ng/dl), and 12% were deficient (<15 ng/dl). Younger age, higher reported dietary vitamin D intake, use of vitamin D supplementation, and increased ambient ultraviolet light were associated with higher serum 25-hydroxyvitamin D levels. There was not enough evidence to suggest treatment type, gender, race, years since diagnosis or BMI were associated with serum 25-hydroxyvitamin D levels. Only 27% of conventional chemotherapy-treated ALL survivors and 8% of HCT-treated ALL survivors met RDA for dietary vitamin D intake.
CONCLUSIONS - The prevalence of vitamin D deficiency and insufficiency in ALL survivors is similar to that of the general pediatric population in the United States, and there is no difference in serum 25-hydroxyvitamin D status between chemotherapy-treated and HCT-treated ALL survivors. ALL survivors rarely meet the RDA requirements for vitamin D. Further studies are needed to determine whether dietary and behavioral interventions can improve the vitamin D status of ALL survivors.
Copyright © 2010 Wiley-Liss, Inc.
INTRODUCTION - Concurrent signal transduction inhibition with the epidermal growth factor receptor (EGFR) inhibitor gefitinib and the mammalian target-of-rapamycin inhibitor everolimus has been hypothesized to result in enhanced antitumor activity in patients with non-small cell lung cancer (NSCLC). This phase II trial assessed the efficacy of the combination of gefitinib and everolimus in patients with advanced NSCLC.
METHODS - Two cohorts of 31 patients with measurable stage IIIB/IV NSCLC were enrolled: (1) no prior chemotherapy and (2) previously treated with cisplatin or carboplatin and docetaxel or pemetrexed. All patients received daily everolimus 5 mg and gefitinib 250 mg. Response was assessed after 1 month and then every 2 months. Pretreatment tumor specimens were collected for mutation testing.
RESULTS - Sixty-two patients were enrolled (median age: 66 years, 50% women, 98% stage IV, all current/former smokers, and 85% adenocarcinoma). Partial responses were seen in 8 of 62 patients (response rate: 13%; 95% confidence interval: 5-21%); five responders had received no prior chemotherapy. Three partial responders had an EGFR mutation. Both patients with a KRAS (G12F) mutation responded. The median time to progression was 4 months. Median overall survival was 12 months, 27 months for no prior chemotherapy patients, and 11 months for patients previously treated with chemotherapy.
CONCLUSIONS - The 13% partial response rate observed did not meet the prespecified response threshold to pursue further study of the combination of gefitinib and everolimus. The response rate in patients with non-EGFR mutant tumors was 8%, likely reflecting activity of everolimus. Further investigation of mammalian target-of-rapamycin inhibitors in patients with NSCLC with KRAS G12F-mutated tumors is warranted.