Pujan Kandel

Pretransplant frailty is associated with decreased survival after lung transplantation

BACKGROUND Frailty is a condition of increased vulnerability to adverse health outcomes. Although frailty is an important prognostic factor for many conditions, the effect of frailty on mortality in lung transplantation is unknown. Our objective was to assess the association of frailty with survival after lung transplantation. METHODS We performed a retrospective cohort analysis of all adult lung transplant recipients at our institution between 2002 and 2013. Frailty was assessed using the frailty deficit index, a validated instrument that assesses cumulative deficits for up to 32 impairments and measures the proportion of deficits present (with frailty defined as >0.25). We examined the association between frailty and survival, adjusting for age, sex, and bilateral (vs single) lung transplant using Cox proportional hazard regression models. RESULTS Among 144 lung transplant patients, 102 (71%) completed self-reported questionnaires necessary to assess the frailty deficit index within 1 year before lung transplantation. Frail patients (n = 46) had an increased risk of death, with an adjusted hazard ratio (HR) of 2.24 (95% confidence interval [CI], 1.22-4.19; p = 0.0089). Frailty was not associated with an increased duration of mechanical ventilation (median, 2 vs 2 days; p = 0.26), intensive care unit length of stay (median, 7.5 vs 6 days; p = 0.36) or hospital length of stay after transplantation (median, 14 vs 10.5 days; p = 0.26). CONCLUSIONS Pre-transplant frailty was independently associated with decreased survival after lung transplantation. Pre-transplant frailty may represent an important area for intervention to improve candidate selection and lung transplant outcomes.

Epidemiology of Pediatric Critical Illness in a Population-Based Birth Cohort in Olmsted County, MN

Objectives: Investigations of pediatric critical illness typically focus on inpatient cohorts drawn from wide referral areas and diverse healthcare systems. Cohorts amenable to investigating the full spectrum of critical illness as it develops within a community have yet to be studied in the United States. Our objective was to provide the first epidemiologic report of the incidence and presentation of pediatric critical illness within a U.S. population-based birth cohort. Design: Retrospective cohort study. Setting: A geographically defined community (Olmsted, MN) with medical record linkage across all health systems. All ICU services are provided within a single children’s hospital. Patients: A birth cohort of children (n =9,441) born 2003–2007 in Olmsted County, MN. Measurements and Main Results: During the study period, there were a total of 15,277 ICU admissions to Mayo Clinic Children’s Hospital. A total of 577 birth cohort children accounted for 824 of these admissions during the 61,770 person-years of follow-up accumulated. Incidence of first-time ICU admission was 9.3 admits per 1,000 person-years. Admission rates were highest in the first year of life and then declined steadily. Respiratory problems were among the most common reasons for admission at any age and diagnoses reflect changes in health risk factors as children grow and develop over time. After 1 year old, a majority of children admitted have preexisting chronic comorbidities and/or prior ICU stays. In-hospital mortality occurred exclusively in children admitted prior to 5 days of age (n = 4). Seven children died after hospital discharge. Conclusions: This is the first report characterizing critical illness within a population-based birth cohort of U.S. children. The results demonstrate the changing incidence, presentation, and healthcare requirements associated with critical illness across the developmental spectrum as a population of children ages.

The Role of Adjunct Imaging in Endoscopic Detection of Dysplasia in Barrett’s Esophagus

Advances in imaging technologies have demonstrated promise in early detection of dysplasia and cancer in Barretts esophagus (BE). Optical chromoendoscopy, dye-based chromoendoscopy, and novel technologies have provided the opportunity to visualize the cellular and subcellular structures. Only narrow-band imaging and acetic acid chromoendoscopy have reached benchmarks for clinical use. Volumetric laser endomicroscopy and molecular imaging are not established for routine use. Best practice in management of BE should be focused on careful endoscopic examination, resection, or ablation of the entire abnormal lesion, as well as the use of available imaging technique that has good diagnostic accuracy.

Colorectal endoscopic mucosal resection (EMR)

Colonoscopy has the benefit of detecting and treating precancerous adenomatous polyps and thus reduces mortality associated with CRC. Screening colonoscopy is the keystone for prevention of colorectal cancer. Over the last 20 years there has been increased in the management of large colorectal polyps from surgery to endoscopic removal techniques which is less invasive. Traditionally surgical resection was the treatment of choice for many years for larger polyps but colectomy poses significant morbidity of 14-46% and mortality of up to 7%. There are several advantages of endoscopic resection technique over surgery; it is less invasive, less expensive, has rapid recovery, and preserves the normal gut functions. In addition patient satisfaction and efficacy of EMR is higher with minor complications. Thus, this has facilitated the development of advanced resection technique for the treatment of large colorectal polyps called as endoscopic mucosal resection (EMR).

The risk of secondary primary malignancy in early stage differentiated thyroid cancer: a US population-based study

protein function, encoding for an altered and non-functional isoform [12,13]. Interestingly from a clinical point of view, bsandwich mutations, such as p.V143A c.428T>C, are considered very promising targets for functional p53 rescue by generic small molecule drugs, able to restore wild-type-like activity [13]. When both alleles encode for a non-functional protein, p53 loses its function of ‘guardian of the genome’, causing high genomic instability and resistance to anticancer drugs [12]. In our case, homozygosity for p.V143A (c.428T>C) mutation could have caused tumor resistance after a prolonged response to trastuzumab. Due to the small size of the liver lesion and the ethical problem of performing a ‘clinically not required’ liver biopsy, it has not been possible to analyze the liver metastasis upfront treatment with trastuzumab. Missing this initial analysis, another hypothesis for the acquired resistance to trastuzumab could be that the mutation already existed when the metastasis first appeared, representing a more malignant subclone from the primary tumor. As regards to the expression of p53, IHC staining is usually used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites, a strong and diffuse pattern of p53 expression (greater than 60% of cells) being associated with a mutated TP53 gene in the most of cases [14]. In our case, IHC was not able to discriminate the heterozygous mutation of TP53 in the primary tumor and the homozygous mutation in the metastatic lesion, both appearing intensely positive. In conclusion, in our case, homozygosity for p.V143A c.428T>C mutation in exon5 of TP53 gene could be the cause of the acquired resistance in the course of trastuzumab therapy. Considering the difficulty to find suitable metastatic tissue specimens for molecular assessments and the uncommon presence of this mutation in gastric cancer, it could be hard to clinically verify this hypothesis, which, in our opinion, could be otherwise tested in vitro on HER2 overexpressing gastric cancer cell lines transfected with the p.V143A c.428T>C mutation.

Adenoma recurrence after endoscopic mucosal resection: propensity score analysis of old and new colonoscopes and Sydney recurrence tool implementation

Background and study aims  Risk factors for colorectal adenoma recurrence after endoscopic mucosal resection (EMR) have been well documented. We assessed the efficacy of the newer 190 colonoscope versus the standard 180 colonoscope for complete resection of lateral spreading lesions. Patients and methods  A single-center, retrospective study of patients who underwent EMR with Olympus 180 or 190 colonoscopes from January 1, 2010 to September 30, 2016. We included patients with lesions ≥ 20 mm and surveillance colonoscopy (SC1) after index EMR. A propensity score approach with inverse probability weighting was used to control for potential confounders. A secondary aim was to identify risk factors for recurrence and assess the applicability of the Sydney EMR recurrence tool (SERT) by grading each lesion of our cohort and analyzing associations with recurrence. Results  Two hundred ninety-one lesions met inclusion criteria for the study. Odds ratio (OR) for recurrence with the 190 colonoscope was 1.06 ( P  = .85). Adenoma size ( P  = .02) and use of argon plasma coagulation (APC; P  < .001) were risk factors for recurrence. Lesions with SERT scores > 0 had a higher recurrence risk during follow-up (32 % vs 21 %; OR 1.71; P  = .05). Lesions with SERT scores = 0 reached a plateau for recurrence at 12 and 18 months in Kaplan-Meier curves. Conclusions  The use of 190 colonoscopes did not measurably affect adenoma recurrence at SC1. Recurrence was associated with adenoma size, complementary APC for resection, and SERT scores > 0. Lesions with SERT scores = 0 that remain negative for recurrence at 18 months may return to routine surveillance.

Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer.