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

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.

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.

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.

A Hybrid Approach to Tea Crop Yield Prediction Using Simulation Models and Machine Learning.

Tea (Camellia sinensis L.) is one of the most highly consumed beverages globally after water. Several countries import large quantities of tea from other countries to meet domestic needs. Therefore, accurate and timely prediction of tea yield is critical. The previous studies used statistical, deep learning, and machine learning techniques for tea yield prediction, but crop simulation models have not yet been used. However, the calibration of a simulation model for tea yield prediction and the comparison of these approaches is needed regarding the different data types. This research study aims to provide a comparative study of the methods for tea yield prediction using the Food and Agriculture Organization (FAO) of the United Nations AquaCrop simulation model and machine learning techniques. We employed weather, soil, crop, and agro-management data from 2016 to 2019 acquired from tea fields of the National Tea and High-Value Crop Research Institute (NTHRI), Pakistan, to calibrate the AquaCrop simulation model and to train regression algorithms. We achieved a mean absolute error (MAE) of 0.45 t/ha, a mean squared error (MSE) of 0.23 t/ha, and a root mean square error (RMSE) of 0.48 t/ha in the calibration of the AquaCrop model and, out of the ten regression models, we achieved the lowest MAE of 0.093 t/ha, MSE of 0.015 t/ha, and RMSE of 0.120 t/ha using 10-fold cross-validation and MAE of 0.123 t/ha, MSE of 0.024 t/ha, and RMSE of 0.154 t/ha using the XGBoost regressor with train test split. We concluded that the machine learning regression algorithm performed better in yield prediction using fewer data than the simulation model. This study provides a technique to improve tea yield prediction by combining different data sources using a crop simulation model and machine learning algorithms.

Continuous glucose monitoring in gastroparesis.

BACKGROUND: Delayed gastric emptying can alter glucose levels in diabetic patients; hyperglycemia can delay gastric emptying. Continuous glucose monitoring (CGM) may be useful to assess the relationship between gastric emptying and blood glucose levels. AIMS: The aims of this study were to compare the postprandial blood glucose profile of patients with type 2 diabetes mellitus (T2DM) with and without gastroparesis, normal subjects, and patients with idiopathic gastroparesis (IG), and also to determine the effect of different meal compositions on glucose regulation in T2DM and normals. METHODS: Seven patients with IG, seven T2DM with gastroparesis, ten non-gastroparetic T2DM, and ten normal subjects underwent CGM during a low fat (Eggbeaters) meal. Glucose profiles were also studied in T2DM and normal subjects after high fat, high fiber, spicy, and Ensure liquid nutrient meals. RESULTS: After the Eggbeaters meal, the glucose profile of IGs and normals were similar. Diabetic patients with gastroparesis had similar peak postprandial blood glucose to nongastroparetic diabetics (231 ± 26 vs. 232 ± 18 mg/dl), but had a higher postprandial blood glucose at the end of the 4 h study (187 ± 26 mg/dl vs. 97 ± 10; P = 0.01). In contrast to normals, non-gastroparetic diabetics had higher mean postprandial blood sugar after the Eggbeaters meal (173 ± 5 mg/dl) compared to high fat (157 ± 3; P = 0.002), spicy (133 ± 2; P < 0.001) and Ensure meals (152 ± 1; P < 0.001). CONCLUSIONS: Blood glucose monitoring provides insight to the presence of gastroparesis in diabetic patients: diabetic gastroparetics had prolonged postprandial hyperglycemic profile as compared to non-gastroparetic diabetics. Of the meals tested, the low fat (Eggbeaters) meal was associated with the highest mean postprandial glucose in diabetics.

Current controversies and advances in the management of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is a lethal disease with a mortality rate that has not significantly improved over decades. This is likely due to several challenges unique to pancreatic cancer. Most patients with pancreatic cancer are diagnosed at a late stage of disease due to the lack of specific symptoms prompting an early investigation. A small subset of patients who are diagnosed at an early stage have a better chance at survival with curative surgical resection, but most patients still succumb to the disease in a few years. The dismal overall prognosis is due to suspected micro-metastasis at an early stage. Due to this reason, there is a recent interest in treating all patients with pancreatic cancers with systemic therapy upfront (including the ones that are surgically resectable). This approach is still not the standard of care due to the lack of robust prospective data available. Recent advancements in treatment regimens of chemotherapy, radiation and immunotherapy have improved the overall short-term survival but the long-term survival still remains poor. Novel approaches in diagnosis and treatment have shown promise in clinical studies but long-term clinical data is lacking. The following manuscript presents an overview of the epidemiology, diagnosis, staging, recent advances, novel approaches and controversies in the management of pancreatic adenocarcinoma.

Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway.

Itraconazole, an FDA-approved antifungal, has antitumor activity against a variety of cancers. We sought to determine the effects of itraconazole on esophageal cancer and elucidate its mechanism of action. Itraconazole inhibited cell proliferation and induced G1-phase cell-cycle arrest in esophageal squamous cell carcinoma and adenocarcinoma cell lines. Using an unbiased kinase array, we found that itraconazole downregulated protein kinase AKT phosphorylation in OE33 esophageal adenocarcinoma cells. Itraconazole also decreased phosphorylation of downstream ribosomal protein S6, transcriptional expression of the upstream receptor tyrosine kinase HER2, and phosphorylation of upstream PI3K in esophageal cancer cells. Lapatinib, a tyrosine kinase inhibitor that targets HER2, and siRNA-mediated knockdown of HER2 similarly suppressed cancer cell growth in vitro Itraconazole significantly inhibited growth of OE33-derived flank xenografts in mice with detectable levels of itraconazole and its primary metabolite, hydroxyitraconazole, in esophagi and tumors. HER2 total protein and phosphorylation of AKT and S6 proteins were decreased in xenografts from itraconazole-treated mice compared to xenografts from placebo-treated mice. In an early phase I clinical trial (NCT02749513) in patients with esophageal cancer, itraconazole decreased HER2 total protein expression and phosphorylation of AKT and S6 proteins in tumors. These data demonstrate that itraconazole has potent antitumor properties in esophageal cancer, partially through blockade of HER2/AKT signaling.

Factors contributing to hospitalization for gastroparesis exacerbations.

BACKGROUND: The clinical course of patients with gastroparesis is characterized by symptomatic exacerbations often necessitating hospitalization. AIMS: To investigate precipitating factors leading to hospitalization for exacerbation of symptoms in patients with gastroparesis. METHODS: This was a retrospective review of 103 admissions (63 patients) for gastroparesis exacerbation. RESULTS: Etiologic categories for gastroparetic patients were diabetic (43%), idiopathic (39%), and post surgical (8%). Poor glycemic control was present in 36%, infection in 19% (12 urinary tract infections and two bacteremia), and noncompliance with or intolerance of, medications in six and 5% of patients, respectively. Fasting morning cortisol concentrations were \3 mcg/dl in 9%. Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were seen in 34 of 65 (52%) and 11 of 50 patients (22%), respectively. No identifiable infection was found in 74 and 45% of patients with elevated ESR and elevated CRP, respectively. ESR and CRP were higher when patients were symptomatic necessitating hospitalization (26.2 +/- 6.6 mm/h and 1.6 +/- 1.0 mg/l) compared with when they were seen in outpatient follow-up and less symptomatic (10.3 +/- 2.9 mm/h and 0.3 +/- 0.1 mg/l; P = 0.0001 and P = 0.211, respectively). CONCLUSIONS: Poor glycemic control, infection, noncompliance with/intolerance of medications, and, perhaps, adrenal insufficiency were contributory factors leading to hospitalizations of gastroparetic patients. Hospitalized patients with gastroparesis exacerbations had elevated ESR and CRP levels. Although many patients with elevated inflammatory markers had evidence of infection, some did not. Assessment of inflammatory markers may help indicate those gastroparetic patients in whom a search for infection should be undertaken.

New Era: Endoscopic treatment options in obesity-a paradigm shift.

The prevalence of obesity continues to rise, and along with it comes a multitude of health-related consequences. The healthcare community has consistently struggled with providing treatment options to obese patients, in part due to the reluctance of patients in pursuing the more effective (yet invasive) surgical approaches such as sleeve gastrectomy and Rou-en-Y gastric bypass. On the other hand, the less invasive approach such as lifestyle/behavioral interventions and pharmacotherapy (Orlistat, Phenteramine, Phentermine/Topiramate, Locaserin, Naltrexon/Buproprion, and Liraglutide) have very limited efficacy, especially in the morbidly obese patients. Despite our best efforts, the epidemic of obesity continues to rise and pose enormous costs on our healthcare system and society. Bariatric endoscopy is an evolving field generated to combat this epidemic through minimally invasive techniques. These procedures can be performed in an ambulatory setting, are potentially reversible, repeatable, and pose less complications than their invasive surgical counterparts. These modalities are designed to alter gut metabolism by means of space occupation, malabsorption, or restriction. In this review we will discuss different bariatric endoscopic options (such as intragastric balloons, endoscopic sleeve gastroplasty, endoscopic aspiration therapies and gastrointestinal bypass sleeves), their advantages and disadvantages, and suggest a new paradigm where providers may start incorporating this modality in their treatment approach for obese patients.

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.

An unusual presentation of a benign pancreatic lesion containing amyloid.

We present a unique case of a benign pancreatic lesion which was positive for amyloid in a 55-year-old female patient without systemic amyloidosis. Further testing revealed islet-type amyloid polypeptide (or amylin), a protein found in various diseases such as diabetes, insulinoma and pancreatic adenocarcinoma-none of which was seen in our patient.

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.

Robotic cystogastrostomy and debridement of walled-off pancreatic necrosis.

Walled-off pancreatic necrosis is a known complication of acute pancreatitis and requires intervention if symptomatic or complicated. Laparoscopic cystogastrostomy as a minimally invasive surgical intervention has been well-described in surgical literature but data on a robotic approach is limited. Here we report a case of robotic cystogastrostomy and debridement of walled-off pancreatic necrosis in a patient with a history of severe biliary pancreatitis.

Survival analysis of veteran patients with pancreatic cancer.

OBJECTIVE: 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. METHODS: Medical records of patients diagnosed with pancreatic cancer in the VA North Texas Health Care System from 2005 to 2010 were retrospectively reviewed. Univariate and multivariate analyses (MVA) were performed and the utility of cancer antigen 19-9 (CA19-9) test was explored. RESULTS: Altogether 109 patients with pancreatic cancer, 89.0% of whom were with adenocarcinoma, were divided into early (n = 62) and late (n = 47) mortality groups. Kaplan-Meier analysis revealed a median survival of 154 days [95% confidence interval (CI) 93-194 days]. On MVA, abdominal pain (OR = 10.6, P = 0.009) and large tumor size (OR = 2.4, P = 0.028) were significantly associated with early mortality, while palliative chemotherapy (OR = 0.048, P = 0.001) and neuroendocrine tumor (OR = 0.009, P = 0.024) were significantly associated with late mortality. Subgroup analyses of adenocarcinoma and late-stage patients revealed similar results. Serum CA19-9 performed poorly as a prognostic indicator in both groups (P = 0.43), in metastatic disease at diagnosis (P = 0.32) and after treatment (P = 0.65). CONCLUSIONS: Abdominal pain and large tumor size portends a poor prognosis in patients with pancreatic cancer. Palliative chemotherapy and surgical intervention may prolong the patient's survival. CA19-9 is not universally reliable for predicting metastasis, survival, or the responses to chemotherapy.

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.

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.