Efficacy and safety of endoscopic submucosal dissection for colorectal dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND/AIMS: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD). METHODS: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity. RESULTS: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc resection, R0 resection, and curative resection rates were 92.5% (95% confidence interval [CI], 87.9%-95.4%; I2=0%), 81.5% (95% CI, 72.5%-88%; I2=43%), and 48.9% (95% CI, 32.1%-65.9%; I2=87%), respectively. The local recurrence rate was 3.9% (95% CI, 2%-7.5%; I2=0%). The pooled rates of bleeding and perforation were 7.7% (95% CI, 4.5%-13%; I2=10%) and 5.3% (95% CI, 3.1%-8.9%; I2=0%), respectively. The rates of metachronous recurrence and additional surgery following ESD were 10% (95% CI, 5.2%-18.2%; I2=55%) and 13% (95% CI, 8.5%-19.3%; I2=54%), respectively. CONCLUSIONS: ESD is safe and effective for the resection of dysplastic lesions in IBD with an excellent pooled rate of en-bloc and R0 resection.

UPLC-Q-TOF-MS profiling of Viola stocksii Boiss. and evaluation of aphrodisiac potential and risk factors associated with erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola stocksii Boiss. locally known as makhni or makhanr booti, is an important medicinal food plant with multiple therapeutic applications, including erectile dysfunction (ED). It is mixed with butter and used for boosting energy and sexual health in the subcontinent. AIMS OF THE STUDY: This study was designed to evaluate the chemical composition, aphrodisiac potential and effect of V. stocksii on the risk factors associated with ED. METHODOLOGY: The hydroethanolic extract of V. stocksii (HEEVS) was prepared through the microwave-assisted extraction (MAE) technique. The chemical composition was evaluated using preliminary phytochemical screening and UPLC-Q-TOF-MS analysis. Metals and minerals analysis was performed by an atomic absorption spectrophotometer. The aphrodisiac activity of HEEVS was evaluated using an in vivo aphrodisiac model established in male albino rats and the effect on various sexual parameters such as mount, intromission, ejaculation frequencies and mount, intromission, ejaculation latencies, postejaculatory interval, penile reflexes and serum hormone concentration were analyzed. The effect of HEEVS on various risk factors associated with ED, including prostate cancer (PC), bacterial infections, diabetes and obesity, was evaluated using various in vitro assays. Moreover, four compounds were selected from the UPLC-Q-TOF-MS profile and evaluated for in silico computational analysis against phosphodiesterase-5 (PDE-5) for possible interaction. FINDINGS: The phytochemical screening revealed the presence of various secondary metabolites in HEEVS, while 58 compounds were tentatively identified in the UPLC-Q-TOF-MS analysis. Various important minerals and metals such as zinc, calcium, cadmium and magnesium were detected in the atomic absorption spectrometry analysis. The in vivo aphrodisiac evaluation showed a significant (p < 0.05) increase in the mount, intromission and ejaculation frequencies and a decrease in the mount, intromission latencies and post-ejaculatory intervals at a dose of 300 mg/kg. A marked (p < 0.05) increase was observed in the concentration of serum testosterone and luteinizing hormones in HEEVS treated animals with a significant increase in total penile reflexes. The extract displayed significant anti-prostate cancer activity and a potential antibacterial spectrum against E. coli and S. aureus, with MIC50 values of 215.72 µg/mL and 139.05 µg/mL, respectively. Similarly, HEEVS was found active towards pancreatic lipase (67.34 ± 1.03%), α-glucosidase (3.87 ± 0.54 mmol ACAE/g d.w.) and α-amylase (6.98 ± 1.63 mmol ACAE/g d.w.). The in silico docking study presented a potential interaction between the selected compounds and residues of the active site of PDE-5. CONCLUSION: This report highlights the aphrodisiac potential of V. stocksii and provides experimental support for its traditional use in ED with an attenuative effect on the risk factors associated with ED. Moreover, the chemical composition displayed the presence of functional phytoconstituents and minerals in HEEVS and paves the way for the isolation of compounds with potent aphrodisiac activity.

Evaluating the Aphrodisiac Potential of Mirabilis jalapa L. Root Extract: Phytochemical Profiling and In Silico, In Vitro, and In Vivo Assessments in Normal Male Rats.

The traditional use of Mirabilis jalapa L. roots to enhance male sexual performance prompted us to assess the in silico, in vitro, and in vivo aphrodisiac activities of its hydroethanolic extract using normal male rats. Spectroscopic characterization indicated the presence of ß-D-glucopyranoside, methyl-1,9-benzyl-2,6-dichloro-9H-purine, and Bis-(2-ethylhexyl)-phthalate; these compounds have a significant inhibitory effect on the phosphodiesterase-5 (PDE-5) enzyme in silico evaluation and minerals (including zinc, cadmium, and magnesium). Other phytochemical analyses revealed the presence of phenolic compounds and flavonoids. These phytochemicals and minerals may contribute to the aphrodisiac activities of the extract. Additionally, the in vivo study revealed that the administration of M. jalapa root extract (300 mg/kg) significantly enhanced (p < 0.01, p < 0.03) mount, intromission, and ejaculation frequencies while significantly (p < 0.05) decreasing the mount and intromission latencies, as well as the post-ejaculatory interval time, in comparison with the standard drugs sildenafil and ginseng, resulting in enhanced erection and sexual performance in the rats. Furthermore, the extract significantly (p < 0.05) increased penile reflexes and also elevated the levels of testosterone and luteinizing hormones. Extract (300 mg/kg) significantly (p < 0.05) inhibited the PDE-5 enzyme in an in vitro study. Concludingly, the comprehensive findings of this study suggest that a standardized herbal extract derived from M. jalapa roots alleviates erectile dysfunction and premature ejaculation in male rats. M. jalapa root extract proved to be an alternative treatment for erectile dysfunction and premature ejaculation.

In vitro, in vivo and in silico evaluation of analgesic, anti-inflammatory, and anti-pyretic activity of salicylate rich fraction from Gaultheria trichophylla Royle (Ericaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. AIM OF THE STUDY: Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. MATERIALS AND METHODS: In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. RESULTS: G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 µg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 µg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region. CONCLUSION: The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine.

Ustekinumab does not increase risk of new or recurrent cancer in inflammatory bowel disease patients with prior malignancy.

BACKGROUND AND AIM: There is limited data on the rate of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a history of prior or current malignancy who are initiated on biologic therapies. Furthermore, there is no data on this topic in patients using ustekinumab. METHODS: The retrospective study included 341 patients with IBD and a history of cancer who were subsequently treated with vedolizumab (VDZ; n = 34), ustekinumab (USK; n = 27), tumor necrosis factor α antagonists (anti-TNF; n = 99), or had no immunosuppressive therapy (control; n = 181). Cox proportional hazard models were developed to determine the independent effect of post-cancer immunosuppressive treatment on the occurrence of incident cancer. RESULTS: Over a median of 5.2 person-years of follow up, cancer recurrence occurred in only one patient on anti-TNF, while new cancers developed in one patient on VDZ, three patients on USK, and six patients on anti-TNF, corresponding to cancer rates of 0.4, 1.8, and 0.7 per 100 person-years, respectively. The rate of incident cancer in control patients was 2.4 per 100 person-years and included 18 new and 9 recurrent cancers. Compared with controls, a stepwise Cox proportional hazards model adjusting for significant covariates found no increased risk of incident cancer in patients receiving post-malignancy treatment with USK (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.25-3.03), VDZ (HR 0.18; 95% CI 0.03-1.35), or anti-TNF (HR 0.47; 95% CI 0.20-1.12). CONCLUSION: Use of biologic therapy in IBD patients with a previous history of malignancy was not associated with an increased risk of new or recurrent cancer.

Assessment of without prescription antibiotic dispensing at community pharmacies in Hazara Division, Pakistan: A simulated client's study.

Antibiotics dispensing without a prescription is an irrational practice and can increase the risk of antibiotic resistance, which is a significant public health concern around the globe. This study was aimed to determine the extent to which antibiotics are supplied without prescription in the community pharmacies (CPs) at Hazara Division from November 2020 to February 2021. The simulated client method (SCM) was used, and the data were gathered, recorded, and analyzed through different statistical methods with descriptive and inferential techniques. The antibiotic dispensing was observed in CPs (90.5%), the most dispensed antibiotics were azithromycin (29.4%) and ciprofloxacin (46.5%) respectively. Furthermore, visited medical stores/ drug outlets, 9.5% of the visited stores denied dispensing of antibiotics because they preferred a referral to visit physicians (23. 9%) and (12.8%) did not had the antibiotics at the time of visits. Antibiotics were more obtainable in retail medical stores (AOR = 8.6, 95 percent Cl: 3.0-24.7; p = 0.001) than in pharmacies. In rural areas antibiotics dispensing was more (p = 0.004) as compared to urban areas. Staff members also had asked about patient's (17.7%) symptoms and drug allergies (12.3% and 3.9%), and (1.5%) they consoled them about their medications. The findings of this study indicate that nonprescription antibiotic sales are very common, despite national rules prohibiting this activity. When the simulated Client requested for any medication to relieve his or her discomfort, many antibiotics were given out without a prescription. Pharmacies/medical stores in Hazara Division selling antibiotics without a prescription are worrying and need immediate action by regulators.

Endoscopic Mucosal Resection for Colonic Mucosal Neoplasia and Evaluation of Long-Term Recurrence: A Single-Center Experience of 500 Cases.

OBJECTIVES: Endoscopic mucosal resection (EMR) is an alternative to surgery for the treatment of large laterally spreading lesions. Residual or recurrent adenoma is a major limitation. This study aimed to quantify early and late recurrences and to assess its associated risk factors. METHODS: The study was a single-center, multiendoscopist, longitudinal study conducted between January 1, 2013 and April 26, 2017. A total of 480 patients with 500 polyps who underwent an endoscopic resection were included. Surveillance colonoscopy (SC) was performed at 4 to 6 months (SC1) and 16 to 18 months (SC2). RESULTS: At SC1, early recurrence was noted in 77 of 354 (21.8%) lesions; 76 (98.7%) were treated endoscopically. The remaining 277 of 354 (78.2%) lesions had no recurrence at SC1; only 41 lesions (15%) were followed up at SC2. Recurrence at SC2 was found in 4 lesions (9.8%), all of which were treated endoscopically. Lesion size >40 mm was associated with recurrence. Recurrence at both SC1 and SC2 was successfully treated endoscopically in 78 of 81 lesions (96.3%). CONCLUSIONS: EMR is an effective, minimally invasive technique for the treatment of large laterally spreading lesions. Although recurrence is a concern, its risk is low (21.8% on SC1 and 9.8% on SC2) and was managed endoscopically in 96.3% cases on follow-up endoscopy.

Risk Factors Associated With Hospital Readmission and Costs for Pouchitis.

Background: Pouchitis is the most common long-term complication in patients with restorative proctocolectomy and ileal pouch-anal anastomosis. This study aimed to identify readmission rates for pouchitis and risk factors associated with readmissions in an extensive national database. Methods: We performed a retrospective analysis using the National Readmission Database to determine if patient demographics and clinical characteristics were predictors of hospital readmission within 30 days for adult patients (age >18 years) discharged with a principal diagnosis of pouchitis (ICD-9 code-569.71) from January 2013 to December 2013. Both univariable and multivariable analyses were performed to assess factors associated with 30-day readmission. Results: A total of 1538 patients with pouchitis who were discharged alive were identified. 10.2% [95% confidence interval: 7.6, 12.7] of these were readmitted within 30 days of discharge. The average days to readmission were 18.6 ± 1.01. Multivariable analysis of risk factors associated with readmission showed older age as a protective factor for readmission [odds ratio (OR) = 0.88 (0.81, 0.96); P < 0.005]. Sex and the presence of permanent ileostomy were not associated with readmission in patients with pouchitis. The length of stay during readmissions was associated with postoperative wound infection [OR = 7.7 (94.0, 11.30); P < 0.001], ileus [OR = 4.5 (1.6, 7.4); P < 0.002], permanent ileostomy [OR = 3.7 (1.7, 5.7); P < 0.001], and long-term use of nonsteroidal anti-inflammatory drugs [OR = 3.2 (1.06, 5.3); P < 0.003]. Conclusions: Readmissions in pouchitis patients are frequent. Long-term use of nonsteroidal anti-inflammatory drugs, ileus, permanent ileostomy, and postoperative wound infection is associated with increased length of stay in readmissions.

Risk Factors Associated With Postendoscopic Mucosal Resection Bleeding in Patients With Cirrhosis: A Retrospective Multicenter Cohort Study.

BACKGROUND AND AIM: There is limited data regarding the safety of endoscopic mucosal resection (EMR) in the cirrhotic population. Our study aimed to evaluate the safety of colonoscopic EMR in cirrhosis. MATERIALS AND METHODS: This was a retrospective review of cirrhotics who underwent colonic EMR at 8 Cleveland Clinic Centers between January 1, 2006, and December 31, 2018. Patient data including polyp details and complications occurring within 30 days of the procedure were noted. Univariable and multivariable logistic regression analyses were conducted to find risk factors for post-EMR bleeding. RESULTS: A total of 238 patients who underwent EMR were included. There were 145 males (60.9%) and the mean age was 61.9±8.6 years. Immediate and delayed bleeding, and postpolypectomy syndrome rates were 9.2%, 5.8%, and 1.3%, respectively. Significant risk factors for postpolypectomy bleeding were: increased age (P=0.001), procedure duration >37 minutes (P=0.001), antiplatelet use within 5 days (P=0.023), and lesion diameter >15 mm (P=0.004). Multivariable analysis revealed independent predictors of procedure-related bleeding: age above 65 years [odds ratio (OR) 2.14, P=0.044], antiplatelet use within 5 days (OR 2.42, P=0.047), right colon polyp (OR 3.51, P=0.001), and lesion diameter >15 mm (OR 3.22, P=0.003). CONCLUSIONS: EMR in cirrhotics has an acceptable bleeding risk. Age above 65 years, right colon polyp, polyp size >15 mm, and use of antiplatelets within 5 days are independent risk factors for bleeding.

The role of oral vancomycin in inducing remission for biologic-experienced ulcerative colitis with concomitant primary sclerosing cholangitis and liver transplantation.

While a minority of patients with ulcerative colitis has primary sclerosing cholangitis (PSC), a significant proportion of patients with PSC have ulcerative colitis. The activity of PSC is usually not commensurate with the degree of concomitant colonic inflammation. Moreover, up to one-third of patients with a history of ulcerative colitis may paradoxically experience worsening of their colonic inflammation despite receiving immunosuppression after liver transplantation for PSC. There is a dearth of data pertaining to the management of ulcerative colitis in this post-transplantation patient population. We hereby delineate the case of a patient with severe refractory ulcerative colitis in the aftermath of liver transplantation due to PSC who eventually responded to oral vancomycin after failure of biologic therapy. Since current data implicate that patients with ulcerative colitis and PSC often present with distinct alterations of their colonic microbiome, oral vancomycin may be conjectured to demonstrate a therapeutic role. In this article, the review of literature suggests that oral vancomycin might indeed be an effective substitute in patients in whom the uptake of biologic agents may be challenging owing to their already immunosuppressed status.

Colorectal surgery obesity-related morbidity during COVID-19.

Tocilizumab, a monoclonal antiinterluekin-6 receptor antibody, has been empirically used in the treatment of cytokine release syndrome associated with severe coronavirus disease 2019 infections. The efficacy and safety of these medications for these patients is unknown. The purpose of this report was to present a case of acute large bowel perforation in a morbidly obese patient with coronavirus disease 2019 pneumonia who received empiric Tocilizumab. This case report analyzes the risks of acute large bowel perforation after using this medication empirically and discusses the appropriate management of this adverse event.

What constitutes urgent endoscopy? A social media snapshot of gastroenterologists' views during the COVID-19 pandemic.

Background and study aims There is a consensus among gastroenterology organizations that elective endoscopic procedures should be deferred during the COVID-19 pandemic. While the decision to perform urgent procedures and to defer entirely elective procedures is mostly evident, there is a wide "middle ground" of time-sensitive but not technically urgent or emergent endoscopic interventions. We aimed to survey gastroenterologists worldwide using Twitter to help elucidate these definitions using commonly encountered clinical scenarios during the COVID-19 pandemic. Methods A 16-question survey was designed by the authors to include common clinical scenarios that do not have clear guidelines regarding the timing or urgency of endoscopic evaluation. This survey was posted on Twitter. The survey remained open to polling for 48 hours. During this time, multiple gastroenterologists and fellows with prominent social media presence were tagged to disseminate the survey. Results The initial tweet had 38,795 impressions with a total of 2855 engagements. There was significant variation in responses from gastroenterologists regarding timing of endoscopy in these semi-urgent scenarios. There were only three of 16 scenarios for which more than 70 % of gastroenterologists agreed on procedure-timing . For example, significant variation was noted in regard to timing of upper endoscopy in patients with melena, with 44.5 % of respondents believing that everyone with melena should undergo endoscopic evaluation at this time. Similarly, about 35 % of respondents thought that endoscopic retrograde cholangiopancreatography should only be performed in patients with choledocholithiasis with abdominal pain or jaundice. Conclusion Our analysis shows that there is currently lack of consensus among gastroenterologists in regards to timing of semi-urgent or non-life-threatening procedures during the COVID-19 pandemic. These results support the need for the ongoing development of societal guidance for these "semi-urgent" scenarios to help gastroenterologists in making difficult triage decisions.

The Effect of Atrial Fibrillation on Inpatient Outcomes of Patients with Acute Pancreatitis: A Two-year National Inpatient Sample Database Study.

Limited published data exist regarding the association of atrial fibrillation (AF) and acute pancreatitis. To test our hypothesis that AF increases mortality and clinical outcomes in patients with acute pancreatitis, we conducted a cross-sectional data review of the National Inpatient Sample (NIS) database. The NIS database was reviewed for the collection of data on patient hospitalizations in 2016 and 2017. Patients diagnosed with acute pancreatitis with and without concomitant AF were included in the analysis. The International Classification of Diseases, 10th revision coding system was used for the variables of interest. The Stata software program (StataCorp LLC, College Station, TX, USA) was used to perform statistical analyses. The chi-squared test or analysis of variance was used to identify differences in demographic characteristics between the groups. The study population included two groups of patients: those with acute pancreatitis only (n = 542,440) and those with both acute pancreatitis and AF (n = 32,790). The group with acute pancreatitis and AF had a two- to threefold higher rate of mortality [adjusted odds ratio (OR): 2.59; 95% confidence interval (CI): 2.04-3.28] and increased length of stay (adjusted OR: 1.28; 95% CI: 1.08-1.48). Also, significantly higher odds of sepsis (adjusted OR: 2.49; 95% CI: 2.06-3.01), congestive heart failure (adjusted OR: 3.16; 95% CI: 2.87-3.49), acute coronary syndrome (adjusted OR: 1.61; 95% CI: 1.17-2.21), stroke (adjusted OR: 3.94; 95% CI: 1.42-10.93), and acute kidney injury (adjusted OR: 1.42; 95% CI: 1.30-1.55) were observed in patients with acute pancreatitis and AF relative to in patients with acute pancreatitis only. Our results suggest AF increases mortality in patients with acute pancreatitis and that patients with acute pancreatitis and AF are at greater risk of worse clinical outcomes.

Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience.

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS: Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS: Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.

Newer Trends in Pancreatic Cancer Treatment: Genetic Alterations and the Role of Immune Therapeutic and Targeted Therapies.

Pancreatic cancer prognosis has remained poor and no significant improvement has been achieved over the past two decades. A number of genetic alterations are found in pancreatic cancer with a complex genome and proteome that needs further research investigation and discovery. There is an urgent need for innovative research findings that would increase the 5-year survival rate in patients with pancreatic ductal carcinoma, which in fact has seen only small increments over the past two decades. Targeting the tumor and modifying the stroma could help improve therapy responses. Genomic medicine is useful in a fraction of patients currently; however, the newer proteomic approaches are potentially more likely to help the majority of patients in the future. Future treatments of pancreatic cancer will likely be based on the development of novel therapies per genomic and proteomic identifications of cellular/immunological processes and molecular pathways as therapeutic targets. Herein, we systematically review the newer trends in pancreatic cancer treatment with emphasis on the genetic alterations and role of immune therapeutics and targeted therapies.

Familial Pancreatic Cancer: A Critical Review.

Up to 20% of patients with pancreatic cancer have a family history of the disease. Familial pancreatic cancer is defined as at least two first-degree relatives with pancreatic cancer that occurs without being part of a cancer syndrome. Although this does not follow a specific Mendelian pattern of inheritance, research is underway to better understand this cohort of patients. Recent expert opinion/recommendations encourage physicians treating patients with pancreatic cancer to ask them to consider having germline testing. Herein, we summarize the current peer-reviewed literature on the most common syndromes associated with pancreatic cancer, associated genetic mutations, and recommendations from various consortia regarding screening strategies. Lastly, we describe the economic impact of pancreatic cancer and the impact of screening tools in high-risk populations.

Gemcitabine: A Review of Chemoresistance in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma, an exocrine tumor, is the most common type of cancer of the pancreas and one of the top five most prominent causes of cancer-associated mortality worldwide. The survival rate for pancreatic cancer is sadly less than 8%. The high fatality rate is partly related to late diagnosis and partly to the aggressive nature of malignant cells that disseminate to nearby tissues at an early stage of the disease, making treatment difficult. Available treatment choices consist of both medical and surgical: removal of the tumor, use of various medications like chemotherapeutic drugs and immunotherapeutic agents, radiation therapy, and targeted drug therapy. Since most patients suffer from advanced cancer at the time of diagnosis, chemotherapy becomes the primary therapeutic option in such cases. Drugs like Gemcitabine, Abraxane, FOLFIRINOX, and newer combination therapies are all effective in management, either curatively or palliatively. However, chemoresistance poses a significant challenge. Several factors, both intrinsic and acquired, are involved in drug resistance. Here, we review the mechanism of action of the first-line chemotherapy drugs in pancreatic cancer and various factors associated with cancer chemoresistance.

A longitudinal analysis of the epidemiology and economic impact of inpatient admissions for chronic pancreatitis in the United States.

BACKGROUND: Chronic pancreatitis (CP) is a chronic, debilitating disorder associated with multiple complications, frequently necessitating hospitalization. The aim of this study was to investigate the longitudinal trends for hospitalization, mean length of stay (LOS), and cost associated with inpatient admissions for CP across the United States. METHODS: Using the Nationwide Inpatient Sample, all hospitalizations between 1997 and 2014 were analyzed. We examined annual data for rate of hospitalization, average LOS and cost for CP inpatient admissions. Trends were described over the surveillance period. RESULTS: Between 1997 and 2014, the number of hospitalizations for patients with a primary discharge diagnosis of CP decreased by 41.5% (P<0.001). While the average LOS decreased by 21.2% from 6.2 days in 1997 to 4.9 days in 2014 (P<0.001), the mean charges for CP-related hospital admissions increased by 308.5% from $12,725 in 1997 to $39,260 (adjusted for inflation) in 2014 (P<0.001). The risk of a discharge for CP significantly increased from 1997-2014 for the 1-17 year age group (relative risk 1.518, 95% confidence interval 1.516-1.520; P<0.0001), while it significantly decreased over time for all the other age groups. CONCLUSIONS: Although it is reassuring that the average LOS has reduced, the cost associated with these hospitalizations has almost tripled. We postulate that the increase in cost is likely attributable to a greater number of studies and/or interventions. In order to deliver more cost-conscious care, further investigation is required into the effect that these additional investigations and interventions have on specific endpoints, including disease-specific and all-cause morbidity and mortality.