TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta analysis.

BACKGROUND: Transarterial radioembolization (TARE) is increasingly used as an alternative to transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). We aimed to perform an overall and individual patient data (IPD) meta-analysis of studies comparing TACE and TARE. METHODS: We performed a systematic literature search using pre-specified keywords with the aid of an informationist for articles from inception to 3/2020. The primary endpoint was overall survival (OS), and the secondary endpoint was time to progression (TTP). RESULTS: Seventeen studies met inclusion criteria with 2465 unique patients, with one randomized trial, 4 prospective studies and 12 retrospective studies. Barcelona Clinic Liver Cancer (BCLC) stage B (42.8%) was the most common stage followed by BCLC A (30.3%) and BCLC C (29.0%). There was no difference in OS between the two modalities (-0.55 months, 95% CI -1.95 to 3.05). In three studies with available TTP data, TARE resulted in a longer TTP than TACE (mean TTP 17.5 vs. 9.8 months; mean TTP difference 4.8 months, 95% CI 1.3-8.3 months). IPD-level meta-analysis of 311 patients from three studies showed no difference in overall OS between the two modalities including among subgroups stratified by tumor stage and liver function. Limitations of the current literature include inconsistent length of follow-up, inconsistency in response criteria, and safety reporting. CONCLUSIONS: Current data suggest TARE provides significantly longer TTP than TACE, although the two treatments do not significantly differ in terms of OS. Given limitations of the current data, there is rationale for prospective studies comparing these modalities.

Bariatric Surgery Lowers the Risk of Major Cardiovascular Events.

OBJECTIVE: This study examines the impact of bariatric surgery on the risk of myocardial infarction, stroke, and a composite of cardiovascular outcomes in a large population cohort. Additionally, the impact of different bariatric surgery procedures on cardiovascular outcomes is assessed and compared. SUMMARY BACKGROUND DATA: Bariatric surgery has been shown to improve comorbid conditions that are associated with cardiovascular disease and death. Few large studies have examined the impact of bariatric surgery on cardiovascular outcomes, and specifically compared the different bariatric procedures. METHODS: A retrospective, observational, matched-cohort study was conducted in adult patients with obesity in New York state from 2006 to 2012. Patients were stratified into 2 groups, based on utilization of bariatric surgery. Patients were further subgrouped based on the types of primary bariatric surgery. The primary endpoint was the development of specific cardiovascular events - myocardial infarction (MI), and stroke; as well as a composite of both events. RESULTS: A total of 328,807 patients, including 60,445 who had undergone bariatric surgery, and 268,362 matched nonsurgical controls were the study cohort for comparing surgical and nonsurgical patients. The risk of composite cardiovascular events decreased in the surgical group [hazards ratio (HR) = 0.48, 95% confidence intervals (CI): 0.45-0.51], as did the risk of MI (HR = 0.39, 95% CI: 0.35-0.42), and stroke (HR = 0.55, 95% CI: 0.51-0.59). Among the surgical cohort, sleeve gastrectomy patients had a higher risk of developing MI, stroke, and any type of cardiovascular event than gastric bypass patients. CONCLUSIONS: Bariatric surgery is associated with decreased risk of significant cardiovascular events compared to nonsurgical controls. In this exploratory analysis, gastric bypass was associated with a lower risk of all cardiovascular events than sleeve gastrectomy.

Comparative perioperative and 5-year outcomes of robotic and laparoscopic or open inguinal hernia repair: a study of 153,727 patients in the state of New York.

OBJECTIVE: This study aimed to examine the perioperative outcomes of robotic inguinal hernia repair as compared to the open and laparoscopic approaches utilizing large-scale population-level data. METHODS: This study was funded by the SAGES Robotic Surgery Research Grant (2019). The New York Statewide Planning and Research Cooperative System (SPARCS) administrative database was used to identify all adult patients undergoing initial open (O-IHR), laparoscopic (L-IHR), and robotic (R-IHR) inguinal hernia repair between 2010 and 2016. Perioperative outcome measures [complications, length of stay (LOS), 30-day emergency department (ED) visits, 30-day readmissions] and estimated 1/3/5-year recurrence incidences were compared. Propensity score (PS) analysis was used to estimate marginal differences between R-IHR and L-IHR or O-IHR, using a 1:1 matching algorithm. RESULTS: During the study period, a total of 153,727 patients underwent inguinal hernia repair (117,603 [76.5%] O-IHR, 35,565 [23.1%] L-IHR; 559 [0.36%] R-IHR) in New York state. Initial univariate analysis found R-IHR to have longer LOS (1.74 days vs. 0.66 O-IHR vs 0.19 L-IHR) and higher rates of overall complications (9.3% vs. 3.6% O-IHR vs 1.1% L-IHR), 30-day ED visits (11.6% vs. 6.1% O-IHR vs. 4.9% L-IHR), and 30-day readmissions (5.6% vs. 2.4% O-IHR vs. 1.2% L-IHR) (p < 0.0001). R-IHR was associated with higher recurrence compared to L-IHR. Following PS analysis, there were no differences in perioperative outcomes between R-IHR and L-IHR, and the difference in recurrence was found to be sensitive to possible unobserved confounding factors. R-IHR had significantly lower risk of complications (Risk difference - 0.09, 95% CI [- 0.13, - 0.056]; p < 0.0001) and shorter LOS (Ratio 0.53, 95% CI [0.45, 0.62]; p < 0.0001) compared to O-IHR. CONCLUSION: In adult patients, R-IHR may be associated with comparable to more favorable 30-day perioperative outcomes as compared with L-IHR and O-IHR, respectively.

The Impact of Telemedicine Adoption on a Multidisciplinary Bariatric Surgery Practice During the COVID-19 Pandemic.

OBJECTIVE: This study aims to show how full-time telemedicine adoption has impacted patient visit volume and attendance in a comprehensive metabolic and weight loss center. SUMMARY BACKGROUND DATA: Elective surgical practices have been profoundly impacted by the global COVID-19 pandemic, leading to a rapid increase in the utilization of telemedicine. The abrupt initiation of audio-video telehealth visits for all providers of a multidisciplinary clinic on March 19 2020 provided unique circumstances to assess the impact of telemedicine. METHODS: Data from the clinical booking system (new patient and follow-up visits) for all clinical provider types of the multidisciplinary metabolic center from the pre-telehealth, post-telehealth, and a 2019 comparative period were retrospectively reviewed and compared. The primary outcome is the change in patient visit volume for all clinical providers from before to after the initiation of telemedicine for both new patient, and follow-up visits. RESULTS: There were a total of 506 visits (162 new patient visits, and 344 follow-ups) in the pre-telehealth period, versus 413 visits (77 new patient visits, and 336 follow-ups) during the post-telehealth period. After telehealth implementation, new visits for surgeons decreased by 75%. Although follow-up visits decreased by 55.06% for surgeons, there was an increase by 27.36% for advanced practitioners. When surgeons were separated from other practitioners, their follow-up visit rate decrease by 55.06%, compared to a 16.08% increase for the group of all other practitioners (P < 0.0001). Dietitians experienced higher rates of absenteeism with new patient visits (10.00% vs 31.42%, P = 0.0128), whereas bariatricians experienced a decrease in follow-up visit absenteeism (33.33% vs 0%, P = 0.0093). CONCLUSIONS: Although new patient visit volume fell across the board, follow-up visits increased for certain nonsurgical providers. This provides a template for adoption of a multidisciplinary telehealth clinic in a post-pandemic world.

Per oral pyloromyotomy utilizing a lesser curvature approach: how we do it.

BACKGROUND: The treatment of gastroparesis refractory to medical therapy has evolved to include purely endoscopic techniques. Per oral pyloromyotomy (POP) has evolved from traditional laparoscopic or open pyloroplasty to become a safe and effective minimally invasive option for patients with gastroparesis. As compared to laparoscopic pyloroplasty (LP), POP produces similar improvements in gastric emptying and symptom mitigation, while having shorter lengths of stay. There are slight variations in technique that vary by institution. Described here is a technique utilizing a lesser curve approach, with a mucosotomy closure using clips in an effort to maximize efficiency of the procedure. METHODS: Preoperative workup includes a scintigraphic gastric emptying study or a wireless motility capsule study, and the Gastroparesis Cardinal Symptom Index (GCSI). After an upper endoscopy, the procedure begins with injection into the submucosal space with methylene blue in saline on the lesser curve, 3-5 cm proximal to the pylorus. A 1.5 cm incision is then made with the ERBE hybrid knife. A submucosal tunnel is created past the distal end of the pylorus, and the muscle is hooked, and divided with the hybrid knife. The mucosotomy is closed with clips (Boston Scientific Resolution 360, Boston, MA) after the completion of the myotomy. Post-operatively, patients are discharged home after an overnight stay with a proton pump inhibitor, sucralfate, and a full liquid diet for 2 weeks. CONCLUSIONS: A lesser curve approach with mucosotomy closure using clips is a safe, effective, and efficient modality for performing POP. As more centers adopt POP as a tool for gastroparesis management, the lesser curve method limits the length of the submucosal tunnel needed, and allows for wide adoption of the technique.

Distalization of Roux-en-Y Gastric Bypass: Lengthening the Biliopancreatic Limb.

Laparoscopic Roux-en-Y gastric bypass is an effective surgical procedure to manage obesity and associated comorbidities. Despite this, some patients experience suboptimal weight loss or weight regain. Several revisional options are available following gastric bypass. Distalization, by increasing the biliopancreatic limb and decreasing the common channel, has been previously shown to improve weight loss with low perioperative morbidity. The impact on weight and nutritional deficiencies is associated with lengths of the different intestinal limbs. Although gastric bypass distalization is an established procedure, in this video we present some technical tips and peals.

Intraoperative Pancreatic Ductoscopy for Ampullary Adenocarcinoma During Pancreatic Resection: A Case Report.

Background: Periampullary neoplasms can be challenging to work up and diagnose preoperatively. Herein, we report the case of a patient whose preoperative workup failed to detect a malignancy, yet, underwent a pylorus-preserving pancreaticoduodenectomy (PPPD) with intraoperative pancreatic ductoscopy (IPD) and was ultimately found to have an ampullary adenocarcinoma. Presentation: A 78-year-old woman presented with 4 weeks of nausea, weight loss, jaundice, and light-colored stools. She underwent outpatient diagnostic studies, including magnetic resonance cholangiopancreatography, endoscopic ultrasound, and endoscopic retrograde cholangiopancreatography with pancreatic duct (PD) stenting and papillotomy. These revealed common bile duct dilatation measuring 2 cm, PD dilatation measuring 7 mm, a 17 mm cyst in the head of the pancreas, and a firm nodule noted between the biliary and pancreatic orifices. Cytologic and pathologic analyses were initially nondiagnostic. A repeat ampullary biopsy was negative for dysplasia and malignancy. A computed tomography scan was then performed and showed cystic pancreatic lesions with pancreatic ductal dilation. Suspicion remained high for periampullary tumor or a main duct intraductal papillary mucinous neoplasm, and the patient underwent a PPPD with IPD and tolerated the procedure well. Her final specimen pathology revealed well-to-moderately differentiated ampullary adenocarcinoma, pancreaticobiliary type with positive nodal disease. Conclusions: Given the relatively poor prognosis of patients with node-positive pancreaticobiliary-type ampullary adenocarcinoma, clinical suspicion should remain high for malignancy in patients with lesions located in the periampullary region and a negative preoperative workup, as aggressive treatment approaches are warranted to maximize their chance for survival.

Perioperative Outcomes and Quality of Life after Repair of Recurrent Hiatal Hernia Are Compromised Compared with Primary Repair.

Paraesophageal hernia repair (PEHR) is burdened by high recurrence rates that frequently lead to redo PEHR. Revisional surgery, because of higher complexity, higher risk of injury, and the intrinsic risk of recurrence, has increased likelihood of higher complication rates and decreased quality of life (QOL) postoperatively. We aimed to compare perioperative outcomes and QOL after revisional and primary PEHR. A retrospective review of all patients who underwent PEHR for a recurrent hernia between January 2011 and July 2016 was completed. These were matched with a contemporary cohort of patients who underwent primary PEHR by age, gender, and BMI. Perioperative measures were compared. The patients were invited to complete the Gastrointestinal Quality of Life Index (GIQLI) to assess response to surgical intervention. There were 24 patients (group 1) who underwent revisional PEHR, and they were matched to 48 patients (group 2) who had a primary hernia repair. Thirteen patients in group 1 responded to the survey (54%), whereas 21 patients' responses were received from group 2 (44%). Conversion rates, LOS, and mean Gastrointestinal Quality of Life Index scores were significantly different between the two groups. Reoperative procedures for paraesophageal and hiatal hernias are burdened by higher conversion rates and length of stay, with similar overall complication rates. Patients who are undergoing repair of a recurrent hernia should be preoperatively counseled, and should have realistic expectations of their GI QOL after surgery.

Preoperative anemia: a common finding that predicts worse outcomes in patients undergoing primary hiatal hernia repair.

BACKGROUND: The increased incidence of anemia in patients with hiatal hernias (HH) and resolution of anemia after HH repair (HHR) have been clearly demonstrated. However, the implications of preoperative anemia on postoperative outcomes have not been well described. In this study, we aimed to identify the incidence of preoperative anemia in patients undergoing primary HHR at our institution and sought to determine whether preoperative anemia had an impact on postoperative outcomes. METHODS: Using our IRB-approved institutional HH database, we retrospectively identified patients undergoing primary HHR between January 2011 and April 2017 at our institution. We identified patients with anemia, defined as serum hemoglobin levels less than 13 mg/dL in men and 12 mg/dL in women, measured within two weeks prior to surgery, and compared this group to a cohort of patients with normal preoperative hemoglobin. Perioperative outcomes analyzed included estimated blood loss (EBL), operative time, perioperative blood transfusions, failed postoperative extubation, intensive care unit (ICU) admission, postoperative complications, length of stay (LOS), and 30-day readmission. Outcomes were compared by univariable and multivariable analyses, with significance set at p < 0.05. RESULTS: We identified 263 patients undergoing HHR. The median age was 66 years and most patients were female (78%, n = 206). Seventy patients (27%) were anemic. In unadjusted analyses, anemia was significantly associated with failed postoperative extubation (7 vs. 2%, p = 0.03), ICU admission (13 vs. 5%, p = 0.03), postoperative blood transfusions (9 vs. 0%, p < 0.01), and postoperative complications (41 vs. 18%, p < 0.01). On adjusted multivariable analysis, anemia was associated with 2.6-fold greater odds of postoperative complications (OR 2.57; 95% CI 1.36-4.86; p < 0.01). CONCLUSIONS: In this study, anemia had a prevalence of 27% in patients undergoing primary HHR. Anemic patients had 2.6-fold greater odds of developing postoperative complications. Anemia is common in patients undergoing primary HHR and warrants consideration for treatment prior to elective repair.

A standardized comparison of peri-operative complications after minimally invasive esophagectomy: Ivor Lewis versus McKeown.

BACKGROUND: While our institutional approach to esophageal resection for cancer has traditionally favored a minimally invasive (MI) 3-hole, McKeown esophagectomy (MIE 3-hole) during the last five years several factors has determined a shift in our practice with an increasing number of minimally invasive Ivor Lewis (MIE IL) resections being performed. We compared peri-operative outcomes of the two procedures, hypothesizing that MIE IL would be less morbid in the peri-operative setting compared to MIE 3-hole. METHODS: Our institution's IRB-approved esophageal database was queried to identify all patients who underwent totally MI esophagectomy (MIE IL vs. MIE 3-hole) from June 2011 to May 2016. Patient demographics, preoperative and peri-operative data, as well as post-operative complications were compared between the two groups. Post-operative complications were analyzed using the Clavien-Dindo classification system. RESULTS: There were 110 patients who underwent totally MI esophagectomy (MIE IL n = 49 [45%], MIE 3-hole n = 61 [55%]). The majority of patients were men (n = 91, 83%) with a median age of 62.5 (range 31-83). Preoperative risk stratifiers such as ECOG score, ASA, and Charlson Comorbidity Index were not significantly different between groups. Anastomotic leak rate was 2.0% in the MIE IL group compared to 6.6% in the MIE 3-hole group (p = 0.379). The rate of serious (Clavien-Dindo 3, 4, or 5) post-operative complications was significantly less in the MIE IL group (34.7 vs. 59.0%, p = 0.013). Serious pulmonary complications were not significantly different (16.3 vs. 26.2%, p = 0.251) between the two groups. CONCLUSIONS: In this cohort, totally MIE IL showed significantly less severe peri-operative morbidity than MIE 3-hole, but similar rates of serious pulmonary complications and anastomotic leaks. These findings confirm the safety of minimally invasive Ivor Lewis esophagectomies for esophageal cancer when oncologically and clinically appropriate. Minimally invasive McKeown esophagectomy remains a satisfactory and appropriate option when clinically indicated.

Surgical approaches to adenocarcinoma of the gastroesophageal junction: the Siewert II conundrum.

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy. PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. CONCLUSIONS: Careful review of the data appear to support the fact that a satisfactory oncologic resection can be achieved via a transabdominal extended total gastrectomy with a slight advantage in terms of perioperative complications, and overall postoperative quality of life. Overall and disease-free survival compares favorably to the transthoracic approach. These results can be achieved with careful selection of patients balancing more than just the Siewert type in the decision-making but considering also preoperative T and N stages, histological type (diffuse type requiring longer margins that are not always achievable via gastrectomy), and the presence of Barrett's esophagus.

A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.

Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.

A cancer cell-line titration series for evaluating somatic classification.

BACKGROUND: Accurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task. Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants. Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies. We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies. RESULTS: Cell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300×. The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology. By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity. In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease. CONCLUSIONS: Our cell-line titration series dataset, along with the associated verification results, was effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development. The data is available for further analysis at the European Genome-phenome Archive under accession number EGAS00001001016. Data access requires registration through the International Cancer Genome Consortium's Data Access Compliance Office (ICGC DACO).

CKM and LILRB5 are associated with serum levels of creatine kinase.

BACKGROUND: Statins (HMG-CoA reductase inhibitors) are the most prescribed class of lipid-lowering drugs for the treatment and prevention of cardiovascular disease. Creatine kinase (CK) is a commonly used biomarker to assist in the diagnosis of statin-induced myotoxicity but the normal range of CK concentrations is wide, which limits its use as a diagnostic biomarker. METHODS AND RESULTS: We conducted a genome-wide association study of serum CK levels in 3412 statin users. Patients were recruited in Quebec, Canada, and genotyped on Illumina Human610-Quad and an iSelect panel enriched for lipid homeostasis, hypertension, and drug metabolism genes. We found a strong association signal between serum levels of CK and the muscle CK (CKM) gene (rs11559024: P=3.69×10(-16); R(2)=0.02) and with the leukocyte immunoglobulin-like receptor subfamily B member 5 (LILRB5) gene (rs2361797: P=1.96×10(-10); R(2)=0.01). Genetic variants in those 2 genes were independently associated with CK levels in statin users. Results were successfully replicated in 5330 participants from the Montreal Heart Institute Biobank in statin users for CKM (rs11559024: P=4.32×10(-16); R(2)=0.02) and LILRB5 (rs12975366 P=4.45×10(-10); R(2)=0.01) and statin nonusers (P=4.08×10(-7), R(2)=0.01; P=3.17×10(-9), R(2)=0.02, respectively). CONCLUSIONS: This is the first genome-wide study to report on the underlying genetic determinants of CK variation in a population of statin users. We found statistically significant association for variants in the CKM and LILRB5 genes.

Development of a broad-based ADME panel for use in pharmacogenomic studies.

AIM: To optimally address the interindividual variability observed in pharmacokinetic drug response, we have created a custom genotyping panel that interrogates most of the key genetic variations present in a set of 181 prioritized genes responsible for the absorption, distribution, metabolism and excretion (ADME) of many therapeutic agents. This consensus list of genes and variants was based on the ADME core and extended gene lists compiled by a group of pharmaceutical companies as having relevance. Although these pharmacokinetic genes and pathways are well known, tools that can interrogate a large number of these genes simultaneously within a single experiment are not currently available. METHODS: Using novel design strategies, we have developed an optimized and validated ADME genotyping panel, encompassing approximately 3000 variants, that has broad applicability to any study or clinical trial that would benefit from the evaluation of an extensive list of ADME genes. RESULTS & CONCLUSION: Over the course of three design iterations, overall assay conversion rates were improved from 83 to 97% resulting in a panel that fills in many of the gaps in coverage present on currently available commercial genotyping assays. The utility of the assay has been demonstrated by the screening of more than 1000 samples resulting in the discovery of novel pharmacogenomic associations. The assay, and the underlying methods, will continue to be a valuable tool for use in future pharmacogenomic studies.

Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.

In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.

Use of Sequenom sample ID Plus® SNP genotyping in identification of FFPE tumor samples.

Short tandem repeat (STR) analysis, such as the AmpFlSTR® Identifiler® Plus kit, is a standard, PCR-based human genotyping method used in the field of forensics. Misidentification of cell line and tissue DNA can be costly if not detected early; therefore it is necessary to have quality control measures such as STR profiling in place. A major issue in large-scale research studies involving archival formalin-fixed paraffin embedded (FFPE) tissues is that varying levels of DNA degradation can result in failure to correctly identify samples using STR genotyping. PCR amplification of STRs of several hundred base pairs is not always possible when DNA is degraded. The Sample ID Plus® panel from Sequenom allows for human DNA identification and authentication using SNP genotyping. In comparison to lengthy STR amplicons, this multiplexing PCR assay requires amplification of only 76-139 base pairs, and utilizes 47 SNPs to discriminate between individual samples. In this study, we evaluated both STR and SNP genotyping methods of sample identification, with a focus on paired FFPE tumor/normal DNA samples intended for next-generation sequencing (NGS). The ability to successfully validate the identity of FFPE samples can enable cost savings by reducing rework.