Zeeshan Ramzan

Chronic idiopathic constipation: more than a simple colonic transit disorder.

Background: Constipation affects up to 28% of Americans in 4 pathophysiologic patterns: slow transit constipation, dyssynergic defecation, a combination of both, and normal colon transit with normal pelvic floor function. Constipation may be a part of a generalized gastrointestinal (GI) tract transit disorder. The purposes of this study were to determine the percentage of constipated patients with the different pathophysiologic subtypes and and to evaluate what percentage of constipated patients has a diffuse GI tract transit disorder. Methods: This was a retrospective analysis of 212 patients who underwent anorectal manometry for intractable constipation. Results of anorectal manometry, electromyography, balloon expulsion testing, defecography, and whole-gut transit scintigraphy were reviewed. Results: Of 212 patients included in the analysis, 91 (42%) had slow transit constipation, 25 (12%) had dyssynergic defecation, 53 (25%) had both, and 43 (20%) had neither. Of patients (91) with slow transit constipation alone, 31 (34%) had delayed gastric emptying, 9 (10%) had delayed small bowel transit, 7 (8%) had a delay in both, and 41 (48%) had normal upper GI tract transit. A similar distribution of upper GI tract transit disorders was observed for patients with dyssynergic defecation, slow transit constipation and dyssynergic defecation, and normal colon transit with normal pelvic floor function. Conclusions: Patients with chronic idiopathic constipation have a range of colonic motor disorders. The majority (80%) had slow transit constipation, dyssynergic defecation, or a combination of slow transit constipation and dyssynergic defecation. In addition, many patients (51%) with chronic idiopathic constipation have a concurrent upper GI tract transit disorder.

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying.

Background  Symptoms of gastroparesis based on patient recall correlate poorly with gastric emptying. The aim of this study is to determine if symptoms recorded during gastric emptying scintigraphy (GES) correlate with gastric emptying and with symptoms based on patient recall.

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.

Use of Endoluminal Ultrasound to Evaluate Gastrointestinal Motility

The use of high-frequency ultrasound transducers in the gastrointestinal tract (GI) has already yielded remarkable findings concerning the anatomy, physiology and pathophysiology of the GI tract and of various motility disorders. These transducers have made completely invisible portions of the GI tract (the longitudinal smooth muscle, muscles of the upper esophageal sphincter, components of the gastroesophageal junction high-pressure zone, and the muscle of the anal sphincter complex) accessible to investigation. Use of simultaneous ultrasound and manometry has allowed the exploration of the normal physiology of peristaltic contraction. The components of the high-pressure zone of the distal and proximal esophagus have been isolated and the movement of these components has been studied individually and as a group. Various esophageal motility disorders have been investigated including achalasia, scleroderma, Barrett’s esophagus and diffuse esophageal spasm. The possible etiology of the symptoms of esophageal chest pain and heartburn (sustained esophageal contractions of the longitudinal smooth muscle), have been studied. The possible underlying pathophysiology of GERD (the missing gastric clasp and sling fiber pressure profile) has been explored. Three-dimensional high-frequency ultrasound imaging has allowed the peristaltic contraction sequence to be viewed in a completely new and unique manner. The biomechanics of both esophageal contraction and the gastroesophageal junction high-pressure zone have been investigated and the mechanical advantage of esophageal shorting has been studied. The mechanism of action of standard surgical and newer endoscopic therapies for GERD has been defined. Future applications of this technology are limited only by our imagination.

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.

Serum Albumin at Diagnosis is an Independent Predictor of Early Mortality in Veteran Patients with Esophageal Cancer

Abstract Aims: To identify independent factors that could predict mortality within 6 months in a cohort of patients with esophageal cancer. Methods: Esophageal cancer patients were grouped into early (≤6 months, n = 41) and late (>6 months, n = 81) mortality groups. 52 variables were analyzed by univariable analysis (UA). A multivariable (MVA) regression model was created to identify predictors of early mortality. Results: When comparing early and late mortality groups, there was no difference in age, BMI, race, histology, or anatomic location between the two groups. UA demonstrated that the early mortality group had a lower mean albumin level (3.3 ± 0.1 g/dl vs. 3.8 ± 0.1 g/dl; P < 0.001), poorer ECOG performance status (1.9 ± 0.2 vs. 1.1 ± 0.1, P = 0.02), higher WBC count (9.6 ± 0.7 K/µL vs. 8.2 ± 0.3 K/µL, P = 0.04), and were less likely to receive surgery (2.4% vs. 22.2%; P = 0.003), neoadjuvant treatment (4.9% vs. 28.4%; P = 0.009) and definitive chemoradiation (7.3% vs. 27.2%; P = 0.01). MVA revealed that only low albumin at diagnosis was an independent predictor of survival (P = 0.016). Conclusion: Albumin level at diagnosis is an independent predictor of early mortality and might be used with other variables to provide prognostic information for patients and to guide treatment.

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.