Jonah Cohen

Survival of porcine mesenchymal stem cells over the alginate recovered cellular method

Although previous studies have established alginate as a three-dimensional scaffold for chondrogenic differentiation of mesenchymal stem cells (MSCs), little is known about the cytotoxic effects of the polymerizing and chelating reagents used in the alginate recovered cellular method. Swine MSCs (sMSC) were suspended in the polymerizing agent, CaCl(2), and viability was assessed using a trypan blue exclusion assay at intervals over 2 h. MSCs were also suspended in two different chelating agents, 55 mM sodium citrate and 50 mM EDTA, and viability was calculated. Finally, sMSCs and human MSCs were encapsulated and cultured in vitro. The sMSC were collected at day 4 and the cells were recovered by chelation. Encapsulated hMSCs were cultured with TGFβ3 and IGF-1 and assayed by qRT-PCR for collagen types I and II and sox9 with encapsulated human dermal fibroblasts and chondrocytes as controls recovered on days 0, 7, and 14. Only 53% of sMSCs were viable after 10 min in CaCl(2), the standard polymerization period, whereas 94% of encapsulated sMSCs in polymerized alginate were alive at 15 days. After 20 min in chelating agents, sodium citrate and EDTA, only 46% and 17% of the cells, were viable, respectively. The alginate recovered sMSCs yielded 12% survival. Human MSCs upregulated cartilage-specific collagen type II over the 14-day culture. Collagen I remained unchanged in the hMSCs. Alginate is a suitable agent for chondrodifferentiation of MSCs and can be dissolved by chelation, but the agents involved in hydrogel polymerization and cell recovery should be altered to improve MSC survival.

The Complex Role of Anticoagulation in Cirrhosis: An Updated Review of Where We Are and Where We Are Going

Venous thromboembolism (VTE) in cirrhotic patients is an increasingly encountered problem in the daily clinical practice; there is still a debate on the ideal measures to be followed for prophylaxis and treatment of VTE among this population. Although traditionally, liver cirrhosis has been considered a disease with hypocoagulability state and increasing bleeding tendency due to severe homeostatic disruption in liver disease, until recently there is increasing awareness and evidence that cirrhotic patients are not completely protected from thrombotic events although they have an elevated international normalized ratio and auto anticoagulation. Furthermore, hypercoagulability is now an increasingly recognized aspect of chronic liver disease (CLD), and the bleeding risk of VTE prophylaxis and treatment remains unclear. In this review, we provide an updated discussion on the mechanisms involved in hemostasis in CLD as well as on the benefits and complications of anticoagulant therapy in cirrhotic patients. Overall, sufficient evidence exists, promoting the use of anticoagulation in cirrhotic patients for both VTE prophylaxis and treatment in carefully selected patients after consideration of pharmacologic or endoscopic variceal bleeding prophylaxis.

Use of a cap in single-balloon enteroscopy-assisted endoscopic retrograde cholangiography.

BACKGROUND AND STUDY AIM Cannulation of the native papilla in surgically altered anatomy is difficult in endoscopic retrograde cholangiography (ERC). There are limited data regarding the success of single-balloon enteroscopy-assisted ERC (SBE-ERC) in patients with a native papilla and Roux-en-Y gastric bypass. Use of a plastic cap may assist cannulation in these cases. The aim of the current study was to investigate the use of SBE-ERC with a cap (Cap-SBE-ERC) in patients with surgically altered anatomy referred for ERC. PATIENTS AND METHODS Patients with surgically altered anatomy (hepaticojejunostomy, gastric bypass surgery, and Whipples surgery) who underwent Cap-SBE-ERC were identified from a prospectively maintained database. Outcomes were diagnostic and procedural success. Patients with a native papilla were compared with those with a biliary-enteric anastomosis. RESULTS Among 56 patients with surgically altered anatomy, high rates of diagnostic and procedural success were observed (78.6 % and 71.4 %, respectively). High diagnostic and procedural success rates of 72.7 % and 65.9 %, respectively, were also observed for patients with Roux-en-Y gastric bypass anatomy with a native papilla (n = 44). CONCLUSION High rates of diagnostic and procedural success were reported for SBE-ERC with the use of a cap, including a large subgroup of patients with Roux-en-Y gastric bypass and a native papilla.

Computer vision and augmented reality in gastrointestinal endoscopy.

Augmented reality (AR) is an environment-enhancing technology, widely applied in the computer sciences, which has only recently begun to permeate the medical field. Gastrointestinal endoscopy—which relies on the integration of high-definition video data with pathologic correlates—requires endoscopists to assimilate and process a tremendous amount of data in real time. We believe that AR is well positioned to provide computer-guided assistance with a wide variety of endoscopic applications, beginning with polyp detection. In this article, we review the principles of AR, describe its potential integration into an endoscopy set-up, and envisage a series of novel uses. With close collaboration between physicians and computer scientists, AR promises to contribute significant improvements to the field of endoscopy.

The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis.

Background: Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. Methods: Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. Results: Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. Conclusions: Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.

A Novel Opportunity in Minimally Invasive Colorectal Cancer Therapy: Defining a Role for Endoscopic Submucosal Dissection in the United States

Colorectal cancer is the third most common cancer among both men and women in the United States and the second leading cause of cancer death. Endoscopic submucosal dissection (ESD) is an innovative advanced endoscopic therapy for superficial gastrointestinal neoplasms which is rapidly becoming standard of care particularly in Asia. ESD was first developed for the resection of early gastric cancers; yet ESD for colon tumors has gained increasing attention in recent years. The advantage of ESD over conventional endoscopic resection lies in its potential to achieve en bloc resection regardless of tumor size, leading to more precise histological evaluation and greater potential for cure. Selecting appropriate patients for this procedure involves identifying colorectal cancers with nul risk of lymph node spread. For colorectal ESD to engraft in the United States, the prevalence of such early stage lesions must be defined so that centers of excellence can be developed for high volume clinical practice to offer patients the safest and most efficacious outcomes. This review discusses the endoscopic staging of colorectal neoplasms, indications for colorectal ESD, and the epidemiology of early stage ESD-amenable colorectal cancer in America to better define an opportunity for this important minimally invasive therapy.

The Clinical Implications of Fatty Pancreas: A Concise Review

Fatty pancreas is a newly recognized condition which is poorly investigated until today as compared to nonalcoholic fatty liver disease. It is characterized by pancreatic fat accumulation and subsequent development of pancreatic and metabolic complications. Association of fatty pancreas have been described with type 2 diabetes mellitus, acute and chronic pancreatitis and even pancreatic carcinoma. In this review article, we provide an update on clinical implications, pathogenesis, diagnosis, treatment and outcomes.

Learning curve for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions in a novel ex-vivo simulation model

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is essential in the management of digestive cancers. However, teaching and learning this technique remain challenging due to the lack of cost-effective models. Material and methods: This was a prospective experimental study using a complete porcine upper gastrointestinal ex-vivo organ package, placed in an Erlangen Active Simulator for Interventional Endoscopy (EASIE-R), and prepared with one cyst and two solid masses (2 cm). Five fellows inexperienced in EUS-FNA were enrolled, performing 10 procedures on each lesion, alternatively. The total time, number of attempts for success, of needle view losses, and of scope handling were recorded, associated with an independent skills rating by procedure. We compared the first 15 procedures with the last 15 for each fellow. Results: The fellows successfully performed all procedures in 2 to 40 minutes, requiring 1 to 6 attempts. All (5/5) improved their total time taken (P < 0.001), number of times when the EUS view of the needle was lost (P < 0.05), scope handling (P < 0.005), and skills rating (P < 0.001), whereas 4/5 (80 %) improved their number of attempts. The overall evaluation showed a significant decrease (P < 0.001) in the total time taken (11.2 ± 7.8 vs 4.3 ± 2.2 minutes), number of attempts (2.6 ± 1.2 vs 1.2 ± 0.7), number of times when the EUS view of the needle was lost (2.3 ± 2 vs 0.5 ± 0.7), and need for scope handling (1.1 ± 1.7 vs 0.1 ± 0.2). We also observed an improvement in skills rating (5 ± 1.9 vs. 7.7 ± 1.1). Conclusion: This newly designed ex-vivo model seems to be an effective way to improve the initial learning of EUS-FNA, by performing 30 procedures.

Hepatosplenic alpha/beta T-cell lymphoma masquerading as cirrhosis.

A 59-year-old man with diabetes mellitus, prior hepatitis B infection and recently diagnosed cirrhosis with prior Babesiosis presented to our institution from an outside hospital with six months of worsening abdominal pain, myalgias and fevers. On admission, physical examination revealed jaundice, hepatosplenomegaly and diffuse lymphadenopathy. Laboratory investigations demonstrated mild anemia, thrombocytopenia, hyperbilirubinemia and elevated lactate dehydrogenase. Tests for human immunodeficiency virus, and active Babesia microti infection were negative, however Epstein-Barr virus DNA by quantitative PCR was markedly elevated. CT scan revealed features suggestive of a cirrhotic liver without focal mass lesions as well as massive splenomegaly with axillary, retroperitoneal and inguinal lymphadenopathy. Bone marrow and lymph node biopsies were obtained which ultimately revealed hepatosplenic T-cell lymphoma. The patients initial liver biopsy from five months prior to presentation was re-evaluated by our institutions pathologists. Histologic analysis showed hepatic sinusoidal and portal infiltration of atypical lymphocytes morphologically identical to those present on the more recently excised lymph node tissue. The hepatic sinusoidal lymphoid cells were strongly positive for CD2, CD3 and CD5 whereas CD4, CD8 stained only minor subsets of the T cells. Subsequent flow cytometric immunophenotypying of peripheral blood identified T-cell receptor alpha/beta positive cells that lacked CD4 and CD8 (double negative alpha/beta T cells). Given the established bone marrow involvement, he was diagnosed with stage IV disease and treated with chemotherapy. His clinical course involved multiple hospitalizations complicated by hyponatremia, neutropenic fevers and pulmonary emboli. Following his fourth cycle of chemotherapy, he developed worsening liver failure and expired approximately three months after initial diagnosis of lymphoma. Hepatosplenic lymphoma of alpha/beta T cells is a rare malignancy with largely unclear risk factors and varied clinical presentations. Notably, diffuse infiltration of liver parenchyma is a prominent feature and the disease can mimic cirrhosis clinically as well as radiographically. Early recognition of this aggressive lymphoma is important and should be considered in the evaluation of patients in whom the etiology of cirrhosis remains in question.

Integrative Medicine for Gastrointestinal Disease

Gastrointestinal conditions are prevalent in the population and account for significant morbidity and health care costs. Patients with gastrointestinal conditions use integrative medicine. There is growing evidence that integrative medicine approaches can improve symptoms and affect physiology and disease course. This article reviews data on some common and well-studied approaches, including mind-body therapies, acupuncture, diet, probiotics, and dietary supplements and herbs. Although clear recommendations can be made for some conditions, in others there are challenges in translating these findings owing to small study size, lack of standardization, and trial heterogeneity.