The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers

Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of EGC to AGC, it is required to disclose EGC and AGC genomes in mutational and evolutionary perspectives. We performed whole‐exome sequencing and copy number profiling of nine microsatellite (MS)‐unstable (MSI‐H) (five EGCs and four AGCs) and eight MS‐stable (MSS) gastric cancers (four EGCs and four AGCs). In the cancers, we observed well‐known driver mutations (TP53, APC, PIK3CA, ARID1A, and KRAS) that were enriched in cancer‐related pathways, including chromatin remodelling and tyrosine kinase activity. The MSI‐H genomes harboured ten times more mutations, but were largely depleted of copy number alterations (CNAs) compared to the MSS cancers. Interestingly, EGC genomes showed a comparable level of mutations to AGC in terms of the number, sequence composition, and functional consequences (potential driver mutations and affected pathways) of mutations. Furthermore, the CNAs between EGC and AGC genomes were not significantly different in either MSI‐H and MSS. Evolutionary analyses using somatic mutations and MSI as molecular clocks further identified that EGC genomes were as old as AGC genomes in both MSS and MSI‐H cancers. Our results suggest that the genetic makeup for gastric cancer may already be achieved in EGC genomes and that the time required for transition to AGC may be relatively short. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful in the clinical settings for the molecular diagnosis and therapeutics of gastric cancer patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Risk prediction platform for pancreatic fistula after pancreatoduodenectomy using artificial intelligence

BACKGROUND Despite advancements in operative technique and improvements in postoperative managements,postoperative pancreatic fistula(POPF) is a life-threatening complication following pancreatoduodenectomy(PD).There are some reports to predict POPF preoperatively or intraoperatively,but the accuracy of those is questionable.Artificial intelligence(AI) technology is being actively used in the medical field,but few studies have reported applying it to outcomes after PD.AIM To develop a risk prediction platform for POPF using an AI model.METHODS Medical records were reviewed from 1769 patients at Samsung Medical Center who underwent PD from 2007 to 2016.A total of 38 variables were inserted into AI-driven algorithms.The algorithms tested to make the risk prediction platform were random forest(RF) and a neural network(NN) with or without recursive feature elimination(RFE).The median imputation method was used for missing values.The area under the curve(AUC) was calculated to examine the discriminative power of algorithm for POPF prediction.RESULTS The number of POPFs was 221(12.5%) according to the International Study Group of Pancreatic Fistula definition 2016.After median imputation,AUCs using 38 variables were 0.68 ± 0.02 with RF and 0.71 ± 0.02 with NN.The maximal AUC using NN with RFE was 0.74.Sixteen risk factors for POPF were identified by AI algorithm:Pancreatic duct diameter,body mass index,preoperative serum albumin,lipase level,amount of intraoperative fluid infusion,age,platelet count,extrapancreatic location of tumor,combined venous resection,co-existing pancreatitis,neoadjuvant radiotherapy,American Society of Anesthesiologists' score,sex,soft texture of the pancreas,underlying heart disease,and preoperative endoscopic biliary decompression.We developed a web-based POPF prediction platform,and this application is freely available at http://popfrisk.smchbp.org.CONCLUSION This study is the first to predict POPF with multiple risk factors using AI.This platform is reliable(AUC 0.74),so it could be used to select patients who need especially intense therapy and to preoperatively establish an effective treatment strategy.     

Effects of bariatric surgery on metabolic and nutritional parameters in severely obese Korean patients with type 2 diabetes: A prospective 2‐year follow up

Aims/Introduction

Little is known about the long‐term effects of Roux‐en‐Y gastric bypass (RYGB) in severely obese Asian individuals.

Methods and Materials

A total of 33 severely obese patients with type 2 diabetes underwent RYGB. All patients were followed up for 2 years. Visceral and abdominal subcutaneous fat areas were assessed using computed tomography (CT) before, and 12 and 24 months after RYGB. The muscle attenuation (MA) of paraspinous muscles observed by CT were used as indices of intramuscular fat.

Results

The mean percentage weight loss was 22.2 ± 5.3% at 12 months, and 21.3 ± 5.1% at 24 months after surgery. Compared with the baseline values, the visceral fat area was 53.6 ± 17.1% lower 24 months after surgery, and the abdominal subcutaneous fat area was 32.7 ± 16.1% lower 24 months after surgery. The MA increased from 48.7 ± 10.0 at baseline to 52.2 ± 8.9 (P = 0.009) 12 months after surgery. The MA after the first 12 months maintained changes until 24 months. Triglycerides and free fatty acids were reduced after surgery, whereas the high‐density lipoprotein cholesterol levels were increased significantly after surgery. At the last follow‐up visit, 18 patients (55%) had diabetes remission. The percentage of iron and vitamin D deficiency was 30% and 52%, respectively.

Conclusions

We found that patients subjected to RYGB had significant sustained reductions in visceral and intramuscular fat. There were durable improvements in the cardiometabolic abnormalities without any significant comorbidities. However, there were mild nutritional deficiencies in these patients despite daily supplementation with multivitamins and minerals.     

Nonsurgical and nonprosthetic camouflage treatment of skeletal Class II open bite with bilaterally missing lower first molars

This report illustrates the successful nonsurgical and nonprosthetic camouflage treatment of a skeletal Class II open bite malocclusion combined with missing mandibular first molars bilaterally. In the mandible, the second and third molars were uprighted and protracted, substituting for the missing first molars. In the maxilla, anterior bodily retraction and full-arch intrusion were achieved following premolar and second molar extraction, which also induced autorotation of the mandible. The treatment outcome and prognosis were confirmed with three-dimensional superimposition techniques, along with long-term stability.