Ammar B. Nassri

The role of Botulinum toxin injection in the management of achalasia.

Purpose of review Botulinum toxin injection into the lower esophageal sphincter is an established therapy for the treatment of achalasia. This review will highlight recent studies that shed light on the role of Botulinum toxin injection in the management of achalasia. Recent findings Recent studies have shown that Botulinum toxin injection is the most common initial endoscopic therapy for achalasia, most likely due to its safety and ease of administration. However, this trend represents a deviation from recent guidelines which consider Botulinum toxin injection less efficacious than alternative treatments like pneumatic dilation and laparoscopic Heller myotomy. Over the past decade, multiple commercial formulations of Botulinum toxin injection have been introduced, but the techniques, indications, and therapeutic efficacy for Botulinum toxin have largely remained unchanged. This review will evaluate recent guidelines, consensus articles, meta-analyses, and landmark studies to expound on the short and long-term efficacy of Botulinum toxin, injection dosages, and technique, as well as its efficacy compared to pneumatic dilation, myotomy, and combination therapy. Summary Despite its relatively poor long-term efficacy, Botulinum toxin injection continues to play an important role in elderly patients with comorbidities and as salvage therapy for achalasia.

Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

Due to a wide range of clinical response in patients undergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment. Despite extensive research in this field, the exact mechanisms still remain elusive. Data raging from DNA-repair to specific molecules leading to cell survival as well as resistance to apoptosis have been investigated. Individually, or in combination, there is no single pathway that has become clinically applicable to date. In the following review, we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer.

The use of imaging and biomarkers in diagnosing Barrett’s esophagus and predicting the risk of neoplastic progression

Long-standing gastroesophageal reflux disease can result in transformation of the normal squamous lining of the esophagus into columnar epithelium (with goblet cells). This condition, Barrett’s esophagus (BE), is considered a risk factor for esophageal cancer (EAC) and may be the cause of the increased incidence of EAC over the last few decades. Currently, endoscopy with biopsies revealing dysplasia is the best predictor for neoplastic progression in patients with BE. However, the use of more sophisticated imaging techniques and biomarkers with or without histological assessment may be helpful in more accurate prediction of malignant transformation in these patients. New approaches to the evaluation of BE such as epigenetics, miRNA analysis, detection of DNA content abnormalities and loss of heterozygosity have great potential to shed light on the complex gastroesophageal reflux disease –BE–EAC sequence.

Survival analysis of veteran patients with pancreatic cancer

For patients with pancreatic cancer, the identification of reliable predictors of their outcomes could be invaluable for directing the managements. This study aimed to identify clinical and laboratory factors that could be used to predict early (≤6 months) or late (>6 months) mortality.

Lymphocyte-to-monocyte ratio can predict mortality in pancreatic adenocarcinoma

AIM To determine if the lymphocyte-to-monocyte ratio (LMR) could be helpful in predicting survival in patients with pancreatic adenocarcinoma. METHODS We retrospectively reviewed the medical records of all patients diagnosed with pancreatic adenocarcinoma in the VA North Texas Healthcare System from January 2005 to December 2010. The LMR was calculated from peripheral blood cell counts obtained at the time of diagnosis of pancreatic cancer by dividing the absolute lymphocyte count by the absolute monocyte count. A Univariable Cox regression analysis was performed using these data, and hazard ratios (HR) and 95%CI were calculated. The median LMR (2.05) was used to dichotomize patients into high-LMR and low-LMR groups and the log rank test was used to compare survival between the two groups. RESULTS We identified 97 patients with pancreatic adenocarcinoma (all men, 66% white, 30% African-American). The mean age and weight at diagnosis were 66.0 ± 0.9 (SEM) years and 80.4 ± 1.7 kg respectively. Mean absolute lymphocyte and monocyte values were 1.50 ± 0.07 K/μL and 0.74 ± 0.03 K/μL respectively. Mean, median and range of LMR was 2.36, 2.05 and 0.4-12 respectively. In the univariable Cox regression analysis, we found that an increased LMR was a significant indicator of improved overall survival in patients with pancreatic adenocarcinoma (HR = 0.83; 95%CI: 0.70-0.98; P = 0.027). Kaplan-Meier analysis revealed an overall median survival of 128 d (95%CI: 80-162 d). The median survival of patients in the high-LMR (> 2.05) group was significantly greater than the low-LMR group (≤ 2.05) (194 d vs 93 d; P = 0.03), validating a significant survival advantage in patients with a high LMR. CONCLUSION The LMR at diagnosis is a significant predictor for survival and can provide useful prognostic information in the management of patients with pancreatic adenocarcinoma.

Epidemiology and Survival of Esophageal Cancer Patients in an American Cohort

Objectives This study seeks to delineate trends in esophageal cancer patients in an American cohort and, in particular, examine the impact of race and histology on survival. Methods The association between over 50 variables between histology and race subgroups was evaluated. Survival was calculated using Kaplan-Meier curves and a multivariable Cox regression analysis (MVA) was performed. Results Poorer survival was noted in black vs. white (193 ± 65 days vs. 254 ± 39, 95% CI 205-295, p=0.07) and squamous cell cancer (SCC) vs. adenocarcinoma (AC) (233 ± 24 days vs. 303 ± 48, 95% CI 197-339, p=0.01) patients. In patients with resectable cancer, blacks had poorer survival than whites (253 ± 46 days vs. 538 ± 202, 95% CI 269-603, p=0.03), and SCC had poorer survival than AC (333 ± 58 vs. 638 ± 152 days, 95% CI 306-634, p=0.006). A higher percentage of white patients received surgery compared to black patients (36% vs. 8%, p=0.08). MVA revealed that only surgery was an independent predictor of mortality (p=0.001). Conclusion Black race and SCC were associated with poorer survival. On MVA, surgery was an independent predictor of mortality. Clinicians should be aggressive in offering potentially curative procedures to patients and eliminating socioeconomic barriers.

Pharmacotherapy for the management of achalasia: Current status, challenges and future directions

This article reviews currently available pharmacological options available for the treatment of achalasia, with a special focus on the role of botulinum toxin (BT) injection due to its superior therapeutic effect and side effect profile. The discussion on BT includes the role of different BT serotypes, better pharmacological formulations, improved BT injection techniques, the use of sprouting inhibitors, designer recombinant BT formulations and alternative substances used in endoscopic injections. The large body of ongoing research into achalasia and BT may provide a stronger role for BT injection as a form of minimally invasive, cost effective and efficacious form of therapy for patients with achalasia. The article also explores current issues and future research avenues that may prove beneficial in improving the efficacy of pharmacological treatment approaches in patients with achalasia.

Tu1952 Survival Analysis of Veteran Patients With Resectable Pancreatic Tumors With and Without Surgery

INTRODUCTION: Treatment of pancreatic cancer depends on the stage of disease. For patients with tumors deemed resectable, the best chance for prolonged survival is with early curative resection. However, it is not clear that this is the best general approach because of the high morbidity and mortality of pancreatic resection, and because tumors often are found to be unresectable at the time of surgery. The aim of this study was to compare survivals of patients who had early curative resection of their pancreatic tumors with those who did not. METHODS: We reviewed medical records of all patients diagnosed with pancreatic cancer at our VA Medical Center from 2005 through 2010, and gathered data on multiple demographic and clinical variables. Survivals of patients with and without tumor resection were compared using Kaplan Meier analysis. RESULTS: We identified 116 patients with pancreatic cancer (all men, 66% white, 29% black, 90% adenocarcinoma, 8% neuroendocrine tumor). Tumor location was head (66%), body (10%), tail (16%) and body/tail of pancreas (4%). Stage at presentation was: I (3%); II (22%); III (12%); IV (63%). 28 patients had tumors deemed resectable (group R) (mean age 64±1.7 years [SEM], 64% white, 81% adenocarcinoma), and 88 had non-resectable (group NR) tumors (mean age 67.1±9.7 years, 66% white, 92% adenocarcinoma). Ultimate treatments overall included surgery (21%), neoadjuvant therapy (4%), adjuvant therapy (10%) and palliative chemotherapy (35%). Kaplan-Meier analysis demonstrated an overall median survival of 153 days (95% CI 93195) for the total group of patients with pancreatic cancer. A total of 17 (14.7%) patients underwent surgery with curative intent (group R+) including 13 Whipple procedures and 4 pancreatic tail resections. 11 patients initially deemed resectable did not undergo tumor resection (group R-) because they were later deemed unfit for surgery (n=4), declined surgery (n=1) or were found to have unresectable disease with intraoperative metastases during surgery (n=6). Both groups (R+ and R-) had similar mean ages (63.6±2.2 vs. 64.5±2.7 years, p=0.80), weight at diagnosis (85.7±5.4 vs. 81.2±3.9, p=0.56), race, stage, tumor size, Ca 19-9 and serum albumin levels. Median survival of the R+ group (401±95 days) was significantly longer than that of the Rgroup (162±70, p =0.03) and the NR group (112±33, p=0.0009). Survival for the 6 patients who had surgery revealing unresectable tumors was poorer than that for the 17 patients who had tumor resections with curative intent (R+), but did not reach significance (246.5 days vs. 401 days, p=0.18). CONCLUSIONS: Early surgery for patients with resectable pancreatic cancer is associated with improved survival. The finding of unresectable disease at surgery is a poor prognostic sign, but the surgery itself does not appear to be the factor influencing the shortened survival.