Novel Inflammatory-Nutritional Biomarkers as Predictors of Histological Activity in Crohn's Disease.

BACKGROUND: There has increasingly been an interest in histological remission as a therapeutic endpoint in inflammatory bowel disease. The aim of this study was to evaluate the utility of a variety of inflammatory - nutritional markers for predicting histological disease activity in patients diagnosed with Crohn's disease. METHODS: Patients with Crohn's disease that had requisite endoscopic, pathological, and laboratory data were retrospectively enrolled in the study. Relevant clinical, laboratory, endoscopic, and pathological data were abstracted. The neutrophil:lymphocyte ratio (NLR), lymphocyte:monocyte ratio (LMR), platelet:lymphocyte ratio (PLR), red blood cell distribution width (RDW), modified Glasgow Prognostic score (mGPS), Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk index (GNRI), CRP/Albumin ratio (CAR), Iron:Ferritin ratio (Fe:F) and the Systemic immune inflammation index (SII) were calculated. The cohort was stratified by presence of histological disease on colonoscopy, and groups were compared with appropriate statistical methods. RESULTS: When comparing patients without histological disease to those with disease, there was a statistically significant difference in CAR (2.9 ± 1.5 vs. 4.2 ± 2, p = 0.001), RDW (13.4 ± 1.3 vs. 14.5 ± 1.8, p = 0.008), PNI (52.4 ± 6.2 vs. 47.4 ± 9.3, p = 0.03), and mGPS (0.2 ± 0.4 vs. 0.6 ± 0.7, p = 0.01). For predicting histological activity, ROC analyses indicated an optimal cutoff of 0.3 for CAR (AUC 0.8, PPV 90.5%), 13.5 for RDW (AUC 0.7, PPV 84.1), 86.1 for PNI (AUC 0.7, PPV 86.1) and > 0 for mGPS (AUC 0.6, PPV 85.2%). The NLR, LMR, PLR, GNRI, Fe: F, and SII did not meet statistical significance (p = 0.4, 0.08, 0.2, 0.5, 0.6, and 0.3, respectively). CONCLUSIONS: We report on ten biomarkers, many of them never studied in Crohn's disease, which can help in predicting the presence of active histological disease. Larger prospective studies are needed to investigate the utility of these biomarkers alone and in combination.

Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.

Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.

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.

Endocrine Diseases and the Liver: An Update.

The endocrine system is a complex interconnected system of organs that control corporeal processes and function. Primary endocrine organs are involved in hormonal production and secretion but rely on a bevy of signals from the hypothalamic-pituitary axis and secondary endocrine organs, such as the liver. In turn, proper hepatic function is maintained through hormonal signaling. Thus, the endocrine system and liver are codependent, and diseases affecting either organs can lead to alterations in function within their counterparts. This article explores the hepato-endocrine relationship, including the effects on endocrine diseases on the liver.

Gastric Ulcer as Presentation of HIV-Associated Kaposi Sarcoma and Resolution With HAART Therapy.

Kaposi sarcoma (KS) is a neoplasm of endothelium-derived cells that are associated with human herpesvirus 8 infection. In the setting of HIV, extensive disease typically necessitates highly active antiretroviral therapy in conjunction with chemotherapy. We report a patient who presented with gastrointestinal symptoms and was found to have KS presenting only as cratered gastric ulcers. The patient declined chemotherapy and was treated with highly active antiretroviral therapy alone and had complete resolution of KS on endoscopy and imaging up to 3 years later.

Helicobacter pylori is Associated with Less Fistulizing, Stricturing, and Active Colitis in Crohn's Disease Patients.

Introduction A potential protective role of Helicobacter pylori (HP) infection against the development of Crohn's disease (CD) has been postulated. There is a lack of studies evaluating the association of HP with CD phenotypes. The aim of this study was to investigate the clinical features and disease activity of patients with CD who were diagnosed with HP infection. Methods The charts of 306 consecutive patients from the inflammatory bowel disease (IBD) database at the University of Florida College of Medicine, Jacksonville from January 2014 to July 2016 were reviewed. Ninety-one CD patients who were tested for HP were included, and the frequencies of strictures, fistulas, and colitis in surveillance biopsies in these patients were evaluated. Results Of the 91 CD patients tested for HP, 19 had HP infection. A total of 44 patients had fistulizing/stricturing disease, and 62 patients had active colitis. In the univariate analysis, patients with HP infection had less fistulizing/stricturing disease (21.1% vs. 55.6%, p = 0.009) and less active colitis (42.1% vs. 77.1%, p = 0.005). In the multivariate analysis, HP infection remained as a protective factor for fistulizing/stricturing disease phenotype (OR: 0.22; 95%CI: 0.06-0.97; p = 0.022) and active colitis (OR: 0.186; 95%CI: 0.05-0.65; p = 0.010). Conclusion HP infection was independently associated with less fistulizing/stricturing disease and less active colitis in CD patients. Our study suggests CD patients with a history of HP infection are less prone to complications.

Safety and efficacy of over-the-scope clip-assisted full thickness resection of duodenal subepithelial tumors: A case report.

BACKGROUND: Over-the-scope clip-assisted endoscopic full thickness resection (eFTR) of subepithelial tumors is a novel and promising endoscopic technique. Recently, there have been prospective studies investigating its use for colonic masses, but data regarding its use and efficacy in the duodenum are limited to a few reports. CASE SUMMARY: A 65-year-old African American female presents for evaluation of persistent gastroesophageal reflux disease not responsive to medical treatment. A 1 cm nodule was incidentally found in the duodenum and biopsies revealed a low grade well differentiated neuroendocrine tumor. The nodule was removed using over-the-scope clip-assisted eFTR and pathology revealed clear margins. We review the available literature with a discussion on the efficacy and safety of clip-assisted eFTR s of subepithelial lesions in the duodenum. CONCLUSION: Clip assisted eFTR appears to be a safe and efficacious treatment approach to duodenal subepithelial lesions. Further prospective studies are needed to investigate the long-term utility and safety of clip-assisted eFTR in the management of subepithelial duodenal lesions.

Ipilimumab and Nivolumab induced steroid-refractory colitis treated with infliximab: A case report.

BACKGROUND: A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition. CASE SUMMARY: We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur. CONCLUSION: Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.

Sertraline-Induced Acute Eosinophilic Pneumonia.

BACKGROUND: Acute Eosinophilic Pneumonia (AEP) is a rare, potentially fatal disease often characterized by a short febrile illness, hypoxemic respiratory failure, diffuse pulmonary opacities and evidence of pulmonary eosinophilia. AEP can be idiopathic, but has documented associations with multiple drugs. CASE REPORT: We present the first case highlighting Sertraline specifically as a cause of drug-induced AEP in the English literature.

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.

Pure Testicular Choriocarcinoma with Dermatological, Brain, and Gastrointestinal Metastases.

Testicular choriocarcinoma is a non-seminomatous germ cell tumor (NSGCT) and is the rarest of all testicular cancers. Nearly all choriocarcinomas can be classified as either pure choriocarcinoma or as a component of a mixed germ cell tumor. Pure testicular choriocarcinoma is extremely aggressive and metastasizes early and extensively. We present a case of testicular cancer that metastasized to the skin, gastrointestinal tract, and brain, and discuss the case in light of the available literature.

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.

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.