Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.

Age and the extent of gastrectomy were revealed as the prognostic factors for overall complications and the complications of grade IIIa or over according to the Clavien-Dindo classification following gastrectomy for gastric cancer.

Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic spread of primary tumor to regional lymph nodes in clinical practice. In this research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was developed. The NIR-emitting polymer nanoprobes were designed and synthesized by conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer nanogels. The NIR-PNG nanoprobes were found to be photostable compared with the IRDye800-free dye at room temperature. Upon intradermal injection of the NIR-PNG into the front paw of a mouse, the nanoprobes entered the lymphatic system and migrated to the axillary lymph node within 2 min. The NIR fluorescence signal intensity and retention time of NIR-PNG in the lymph node were superior to the corresponding properties of the IRDye800-free dye. A immunohistofluorescence study of the SLN resected under NIR imaging revealed that the NIR-PNG nanoprobes were predominantly co-localized with macrophages and dendritic cells. Intradermal injection of NIR-PNG nanoprobes into the thigh of a pig permitted real-time imaging of the lymphatic flow toward the SLN. The position of the SLN was identified within 1 min with the help of the NIR fluorescence images. Taken together, the experimental results demonstrating the enhanced photostability and retention time of the NIR-PNG provide strong evidence for the potential utility of these polymer probes in cancer surgery such as SLN mapping.

Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract and is most frequently developed in the stomach in the form of submucosal tumor. The incidence of gastric gastrointestinal stromal tumor is estimated to be as high as 25% of the population when all small and asymptomatic tumors are included. Because gastric gastrointestinal stromal tumor is not completely distinguished from other submucosal tumors, a surgical excisional biopsy is recommended for tumors >2 cm. The surgical principles of gastrointestinal stromal tumor are composed of an R0 resection with a normal mucosa margin, no systemic lymph node dissection, and avoidance of perforation, which results in peritoneal seeding even in cases with otherwise low risk profiles. Laparoscopic surgery has been indicated for gastrointestinal stromal tumors <5 cm, and the indication for laparoscopic surgery is expanded to larger tumors if the above mentioned surgical principles can be maintained. A simple exogastric resection and various transgastric resection techniques are used for gastrointestinal stromal tumors in favorable locations (the fundus, body, greater curvature side). For a lesion at the gastroesophageal junction in the posterior wall of the stomach, enucleation techniques have been tried preserve the organ's function. Those methods have a theoretical risk of seeding a ruptured tumor, but this risk has not been evaluated by well-designed clinical trials. While some clinical trials are still on-going, neoadjuvant imatinib is suggested when marginally unresectable or multiorgan resection is anticipated to reduce the extent of surgery and the chance of incomplete resection, rupture or bleeding.

Preoperative prealbumin levels could be a useful marker for predicting complications, especially infectious complications, after gastric surgery.

Background This study aimed to examine tracers designed to overcome the disadvantages of indocyanine green (ICG), which disperses quickly to multiple lymph nodes, using a near-infrared (NIR) imaging system in animal models. Methods Diluted ICG, ICG/poly-c-glutamic acid (PGA) complex, and IRDye900-conjugated pullulan-cholesterol nanoprobe ''near-infrared polynagogel'' (NIR-PNG) were injected into the stomachs of dogs and pigs, and the patterns of dispersion were observed using an NIR imaging system. To compare retention times, fluorescence signals were evaluated in the stomach and small bowel of animals 1 week after injection.Results A diluted concentration (*0.1 mg/ml) of ICG was optimal for NIR imaging compared with the conventional concentration (5 mg/ml) for visual inspection. When injected into the stomach, the signals of ICG and ICG/PGA complex were relatively large at the injection site, and signals were detected at multiple sentinel nodes and lymph nodes beyond them. The NIR-PNG signal intensity was relatively small at the injection site and limited to only one sentinel node with no additional node. When evaluated 1 week after injection, only the NIR-PNG signal was detected in the canine stomach, and the signal intensity at the lymph nodes of the porcine small bowel was the highest with NIR-PNG, followed by ICG/PGA complex and finally ICG. Conclusion NIR-PNG showed the best characteristics of less dispersion and longer retention in the sentinel nodes, and ICG/PGA complex remained longer than diluted ICG. These tracers could potentially be used as optimal tracers for sentinel node navigation surgery in gastric cancer.

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Objective: To investigate the molecular characteristics of AGEJ compared with EAC and gastric adenocarcinoma. Summary of Background Data: Classification of AGEJ based on differential molecular characteristics between EAC and gastric adenocarcinoma has been long-standing controversy but rarely conducted due to anatomical ambiguity and epidemiologic difference. Methods: The molecular classification model with Bayesian compound covariate predictor was developed based on differential mRNA expression of EAC (N ¼ 78) and GCFB (N ¼ 102) from the Cancer Genome Atlas (TCGA) cohort. AGEJ/cardia (N ¼ 48) in TCGA cohort and AGEJ/upper third GC (N ¼ 46 pairs) in Seoul National University cohort were classified into the EAC-like or GCFB-like groups whose genomic, transcriptomic, and proteomic characteristics were compared. Results: AGEJ in both cohorts was similarly classified as EAC-like (31.2%) or GCFB-like (68.8%) based on the 400-gene classifier. The GCFB-like group showed significantly activated phosphoinositide 3-kinase-AKT signaling with decreased expression of ERBB2. The EAC-like group presented significantly different alternative splicing including the skipped exon of RPS24, a significantly higher copy number amplification including ERBB2 amplification, and increased protein expression of ERBB2 and EGFR compared with GCFB-like group. High-throughput 3D drug test using independent cell lines revealed that the EAC-like group showed a significantly better response to lapatinib than the GCFB-like group (P ¼ 0.015). Conclusions: AGEJ was the combined entity of the EAC-like and GCFB-like groups with consistently different molecular characteristics in both Seoul National University and TCGA cohorts. The EAC-like group with a high Bayesian compound covariate predictor score could be effectively targeted by dual inhibition of ERBB2 and EGFR.