Aline Charabaty

Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety.

BackgroundConcurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC.MethodsPatients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires.ResultsBetween September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment.ConclusionsSBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.

Short- and long-term risk of colorectal adenoma recurrence among whites and blacks.

BACKGROUND It is unclear whether the higher burden from colorectal cancer among blacks is due to an increased biological susceptibility. OBJECTIVE To determine whether non-Hispanic blacks (blacks) have a higher risk of adenoma recurrence than non-Hispanic whites (whites) after removal of colorectal adenoma. DESIGN Secondary analysis of the Polyp Prevention Trial (PPT) data. SETTING United States. PATIENTS Patients were 1668 self-identified whites and 153 blacks who completed the 4-year trial. Of these, 688 whites and 55 blacks enrolled in a posttrial, passive Polyp Prevention Trial Continued Follow-up Study (PPT-CFS) and underwent another colonoscopy. MAIN OUTCOME MEASUREMENTS Recurrence and location of the adenoma and advanced adenoma by race-ethnicity during PPT and cumulative recurrence over a mean follow-up of 8.3 years (range, 4.9-12.4 years) among PPT-CFS enrollees. RESULTS Blacks had similar risk of recurrence of adenoma (39.2% vs 39.4%; incidence risk ratio [RR] = .98; 95% CI, .80-1.20) and advanced adenoma (8.5% vs 6.4%; RR = 1.18; 95% CI, .68-2.05) as whites at the end of PPT. Recurrence risk did not differ by colon subsite. Among PPT-CFS enrollees, the cumulative recurrence rate over a maximal follow-up period of 12 years was similar for blacks and whites for adenoma (67.3% vs 67.0%; RR = 1.01; 95% CI, .84-1.21) and advanced adenoma (14.5% vs 16.9%; RR = 1.03; 95% CI, .60-1.79). LIMITATION There were few blacks in the long-term follow-up study. CONCLUSIONS Adenoma and advanced adenoma recurrence did not differ by race. Our study does not support more frequent surveillance colonoscopies for blacks with a personal history of adenoma as an intervention to reduce colorectal cancer disparity.

Stereotactic Body Radiation Therapy (sbrt) Combined With Chemotherapy for Unresected Pancreatic Adenocarcinoma.

Objectives: The role of radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, stereotactic body radiation therapy (SBRT) delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here, we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer. Materials and Methods: Thirty-eight patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable pancreatic cancer at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over 5 days. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 3. Survival was calculated using the Kaplan-Meier method. Results: The median age was 70 years (range, 45 to 90 y). Eastern Cooperative Oncology Group performance status ranged from 0 to 3. Thirty-four patients received concurrent chemotherapy. Four patients received sequential chemotherapy. Median overall survival was 14.3 months and median progression-free survival was 9.2 months from diagnosis. From radiation, overall survival and progression-free survival were 12.3 and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included 1 grade 3 gastric outlet obstruction, 1 grade 4 biliary stricture, and 1 grade 5 gastric hemorrhage. Conclusions: SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with chemotherapy compare favorably to results obtained with chemotherapy and conventional radiation therapy.

Human Pancreatic Cancer-Associated Stellate Cells Remain Activated after in vivo Chemoradiation

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibrotic reaction or desmoplasia and complex involvement of the surrounding tumor microenvironment. Pancreatic stellate cells are a key mediator of the pancreatic matrix and they promote progression and invasion of pancreatic cancer by increasing cell proliferation and offering protection against therapeutic interventions. Our study utilizes human tumor-derived pancreatic stellate cells (HTPSCs) isolated from fine needle aspirates of pancreatic cancer tissue from patients with locally advanced, unresectable pancreatic adenocarcinoma before and after treatment with full-dose gemcitabine plus concurrent hypo-fractionated stereotactic radiosurgery. We show that HTPSCs survive in vivo chemotherapy and radiotherapy treatment and display a more activated phenotype post-therapy. These data support the idea that stellate cells play an essential role in supporting and promoting pancreatic cancer and further research is needed to develop novel treatments targeting the pancreatic tumor microenvironment.

One Year Recurrence of Aberrant Crypt Foci

Aberrant crypt foci (ACF) are putative precursors of colorectal adenomas and have been postulated as a potential biomarker for colorectal cancer. Few studies have followed subjects after ACF removal to monitor recurrence. Subjects enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were recruited for a study of ACF. A standardized protocol using magnified endoscopy and mucosal staining with methylene blue was implemented to detect rectal ACF. After removal of all baseline ACF, subjects returned 1 year later and recurrent ACF were observed and biopsied. A total of 434 of 505 (86%) subjects observed at baseline returned for the year 1 exam. The mean number of ACF at year 1 was strongly correlated with the number at baseline; subjects with 0, 1, 2 to 3, 4 to 6, and 7+ ACF at baseline had a mean of 1.2, 1.4, 1.7, 3.0, and 5.5 ACF, respectively, at year 1. ACF prevalence and mean count at year 1 (61% and 1.93, respectively), were only slightly lower than the corresponding values at year 0 (69% and 2.25, respectively). The locations of ACF at year 1 and baseline were significantly correlated. Of 96 ACF assessed for histology, 70 (73%) were hyperplastic and none were dysplastic. After removal of ACF at baseline, ACF counts 1 year later were only slightly reduced and were significantly correlated with the baseline ACF count. The results of this study do not support a role for ACF in clinical practice. Cancer Prev Res; 3(7); 839–43. ©2010 AACR.

Diagnosis and Management of Common Gastrointestinal Tract Infectious Diseases in Ulcerative Colitis and Crohnʼs Disease Patients

Abstract:Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohns disease, stretches beyond control of flares. Some infections of the gastrointestinal tract are more commonly seen in patients with IBD. Work from the Human Microbiome Project has been instrumental in our understanding of the interplay between the vast gut microbiota and host immune responses. Patients with IBD may be more prone to infectious complications based on their underlying inflammatory disease and variations in their microbiome. Immunosuppressant medications commonly used to treat patients with Crohns and colitis also play a role in predisposing these patients to acquire these infections. Here, we present a detailed review of the data focusing on the most common infections of the gastrointestinal tract in patients with IBD: Clostridium difficile infections (CDI) and cytomegalovirus (CMV). We will discuss appropriate diagnostic tools and treatment options for these infections. Other less common infections will also be reviewed briefly. Studying the various infections of the gastrointestinal tract in these patients could enhance our understanding of the pathophysiology of IBD.

EBV-associated plasmablastic lymphoma in a patient with Crohn's disease after adalimumab treatment.

Dear Sir, Adalimumab is a third tumor necrosis factor (TNF) inhibitor approved in the US for the treatment of Crohns disease. However, sporadic cases of lympho-proliferative disorders have been reported in association with adalimumab therapy.1,2 In order to fully assess the long-term safety associated with adalimumab and anti-TNF in general, it is necessary to report any drug-associated malignancy, especially when these occur in unusual locations; a prompt diagnosis is crucial to start treatment and increase the chance of patient survival. Herein we report a rare case of EBV-associated plasmablastic lymphoma in a patient with Crohns disease after treatment …

Monitoring inflammatory bowel disease during pregnancy: Current literature and future challenges

Inflammatory bowel disease has a high prevalence in women of childbearing age and can have a significant impact on pregnancy, from conceiving to carrying the pregnancy. Active disease during pregnancy is known to have negative effects on pregnancy outcomes; therefore, careful monitoring during this period is an important but challenging aspect of care and is crucial as it affects important management decisions. Recent data seems to suggest that endoscopy is a relatively safe procedure during all trimesters of pregnancy. Serum biomarkers such as C-reactive protein and fecal calprotectin are helpful non-invasive markers, but have shown conflicting results for correlation with disease activity in some initial studies. Further work is necessary to establish standard of care monitoring during pregnancy.

Emerging Role of Vedolizumab in Managing Refractory Immune Checkpoint Inhibitor–Induced Enteritis

We report a 62-year-old white woman with metastatic choroidal melanoma who developed immune checkpoint inhibitor (ICI)-induced enteritis and grade 3 diarrhea refractory to steroids and infliximab. Her diarrhea quickly resolved after infusion of vedolizumab, and the patient was able to taper down steroids. Vedolizumab’s mechanism of action and its gut specificity have the potential to reverse immune-induced enterocolitis without neutralizing or reversing the therapeutic benefit of ICI on the malignancy.