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Deep neuromuscular block (NMB) has been increasingly utilized, but its role in reducing intraoperative opioid requirement has yet to be investigated. Surgical pleth index (SPI) quantifies nociception. We investigated the effects of deep NMB on SPI-guided remifentanil administration in laparoscopic herniorrhaphy. Total 128 patients undergoing laparoscopic inguinal herniorrhaphy were randomly allocated to two groups of NMB: deep (n = 64) and moderate (n = 64). The remifentanil dose was assessed during intubation, from skin incision until CO2 insertion, and pneumoperitoneum. Mean infusion rate of remifentanil during pneumoperitoneum was higher in moderate NMB group than in deep NMB group (0.103 [0.075–0.143] µg/kg/min vs. 0.073 [0.056–0.097] µg/kg/min, p p = 0.016). The duration of post-anesthesia care unit stay was longer in the moderate NMB group (40 [30–40] min vs. 30 [30–40] min, p = 0.045). In conclusion, deep NMB reduced the remifentanil requirement compared with moderate NMB in SPI-guided anesthesia for laparoscopic herniorrhaphy.

Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.To investigate the underlying mechanism involved in the regulation of gastric cancer (GC) progression by hypoxic CAFs, we performed secretome profiling. Normoxic or hypoxic CAFs conditioned media (CM) were filter-concentrated and in-gel trypsin digested. Resulting peptides were analyzed with LC-MS/MS.We observed that CM derived from hypoxic CAFs could promote migration of a panel of GC cell lines (AGS, SNU668, SNU638). Mass spectrometry analysis of hypoxic or normoxic CAFs CM identified 1595 proteins, of which 19 proteins (10 upregulated and 9 downregulated) were differentially expressed in the hypoxic secretome. We focused on COL4A2, whose expression was significantly decreased in hypoxic CAFs in HIF-1α-independent manner. Silencing of COL4A2 expression in normoxic CAFs phenocopied the effect of hypoxic CAFs in promoting GC cell migration.The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC.

Diffuse type gastric cancer (DGC), represented by low sensitivity to chemotherapy and poor prognosis, is a heterogenous malignancy in which patient subsets exhibit diverse oncological risk-profiles. This study aimed to develop molecular biomarkers for robust prognostic risk-stratification and improve survival outcomes in patients with diffuse type gastric cancer (DGC). We undertook a systematic and comprehensive discovery and validation effort to identify recurrence prediction biomarkers by analyzing genome-wide transcriptomic profiling data from 157 patients with DGC, followed by their validation in 254 patients from 2 clinical cohorts. Genome-wide transcriptomic profiling identified a 7-gene panel for robust prediction of recurrence in DGC patients (AUC = 0.91), which was successfully validated in an independent dataset (AUC = 0.86). Examination of 180 specimens from a training cohort allowed us to establish a gene-based risk prediction model (AUC = 0.78; 95% CI 0.71–0.84), which was subsequently validated in an independent cohort of 74 GC patients (AUC = 0.83; 95% CI 0.72–0.90). The Kaplan–Meier analyses exhibited a consistently superior performance of our risk-prediction model in the identification of high- and low-risk patient subgroups, which was significantly improved when we combined our gene signature with the tumor stage in both clinical cohorts (AUC of 0.83 in the training cohort and 0.89 in the validation cohort). Finally, for an easier clinical translation, we established a nomogram that robustly predicted prognosis in patients with DGC. Our novel transcriptomic signature for risk-stratification and identification of high-risk patients with recurrence could serve as an important clinical decision-making tool in patients with DGC.

Linear-shaped gastroduodenostomy (LSGD) is a new method of intracorporeal reconstruction that is simpler to perform and associated with a lower rate of bile reflux than delta-shaped anastomosis. Here, we analyzed the learning curve of LSGD in totally laparoscopic distal gastrectomy. The cumulative sum method was used to retrospectively analyze consecutive gastric cancer patients undergoing intracorporeal gastroduodenostomy after distal gastrectomy between January 2009 and May 2016. The duration of surgery, postoperative complications, hospital stay, and endoscopic findings in the postoperative period and the first, third, and fifth year were evaluated according to the two phases of the learning curve (learning period versus mastery period). Data from 222 patients were included in the analysis. The LSGD learning period was 29 cases. The surgical time in mastery period was significantly shorter than the learning period (124.9 ± 34.5 versus 168.2 ± 42.0 min, p

Gastrokine 1 (GKN1) plays important roles in maintaining mucosal homeostasis, and in regulating cell proliferation and differentiation. Here, we determined whether GKN1 is a potential theragnostic marker for gastric cancer. We identified GKN1 binding proteins using the protein microarray assay and investigated whether GKN1 is one of the exosomal cargo proteins by western blot, immunoprecipitation, and immunofluorescent assays. Cell proliferation and apoptosis were analyzed by MTT, BrdU incorporation, flow cytometry, and western blot assays. We further validated the functional relevance of exosomal GKN1 in MKN1-injected xenograft mice. The possibility of serum GKN1 as a diagnostic marker for gastric cancer was determined by ELISA assay. In protein microarray assay, GKN1 binding to 27 exosomal proteins was clearly observed. GKN1 was expressed in exosomes derived from HFE-145 gastric epithelial cells by western blot and immunofluorescent assays, but not in exosomes from AGS and MKN1 gastric cancer cells. Exosomes carrying GKN1 inhibited cell proliferation and induced apoptosis in both AGS and MKN1 cells, and exosomes carrying GKN1-treated nude mice-bearing MKN1 xenograft tumors exhibited significantly reduced tumor volume and tumor weight. Silencing of clathrin markedly down-regulated the internalization of exosomal GKN1. Interestingly, serum GKN1 concentrations in patients with gastric cancer were significantly lower than those in healthy individuals and patients with colorectal and hepatocellular carcinomas. The GKN1 is secreted and internalized in the gastric epithelium by exosome-driven transfer, which inhibits gastric tumorigenesis and supports the clinical application of GKN1 protein in gastric cancer diagnosis and treatment.

Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients. This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed. The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC. This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.

The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P = 0.045), large tumor size (P = 0.007), higher T category (P

The role of palliative surgical resection in recurrent or metastatic gastric cancer is still controversial. A retrospective review was conducted on 689 patients who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 382) gastric cancer. Among 131 patients (89 primary metastatic and 42 recurrent) with surgical resection before chemotherpay, 75 underwent gastrectomy, 42 metastasectomy, and 14 gastrectomy with metastasectomy. The median overall survival (OS) of patients who underwent surgical resection was significantly longer than that of patients who received chemotherapy alone (18 vs. 9 months, p p p p pensity score matching. In addition, the median OS of patients who underwent gross complete resection (n = 54) was significantly longer than that of patients who underwent incomplete resection (n = 77) (30 vs. 15 months, p = 0.002). The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer patients may result in a favorable outcome, especially when complete resection is achievable.

Background: Despite the well-described benefits of laparoscopic surgery such as lower operative blood loss and enhanced postoperative recovery in gastric cancer surgery, the application of laparoscopic surgery in patients with locally advanced gastric cancer (AGC) remains elusive owing to a lack of clinical evidence. Recently, the Korean Laparoscopic Surgical Society Group launched a new multicenter randomized clinical trial (RCT) to compare laparoscopic and open D2 lymphadenectomy for patients with locally AGC. Here, we introduce the protocol of this clinical trial. Methods/design: This trial is an investigator-initiated, randomized, controlled, parallel group, non-inferiority trial. Gastric cancer patients diagnosed with primary tumors that have invaded into the muscle propria and not into an adjacent organ (cT2–cT4a) in preoperative studies are recruited. Another criterion for recruitment is no lymph node metastasis or limited perigastric lymph node (including lymph nodes around the left gastric artery) metastasis. A total 1,050 patients in both groups are required to statistically show non-inferiority of the laparoscopic approach with respect to the primary end-point, relapse-free survival of 3 years. Secondary outcomes include postoperative morbidity and mortality, postoperative recovery, quality of life, and overall survival. Surgeons who are validated through peer-review of their surgery videos can participate in this clinical trial. Discussion: This clinical trial was designed to maintain the principles of a surgical clinical trial with internal validity for participating surgeons. Through the KLASS-02 RCT, we hope to show the efficacy of laparoscopic D2 lymphadenectomy in AGC patients compared with the open procedure. Trial registration: ClinicalTrial.gov, NCT01456598.

Background The benefits of preoperative 18FDG-PET/CT for gastric cancer remain uncertain. The aim of this study was to investigate the effects of preoperative 18FDG-PET/CT on the surgical strategy for locally advanced gastric cancer retrospectively. Methods From January 2007 to November 2008, 18FDG-PET/CT was performed in 142 patients who had been diagnosed with advanced gastric cancer by computed tomography or gastrofiberscope findings. Results Detection rates were 88.7% (126/142) for primary tumors and 24.6% (35/142) for local lymph nodes (LN). Nine patients with metastatic lesions underwent induction chemotherapy without operation. Of 133 patients subjected to operation, positive FDG uptake in primary tumors (p = 0.047) and local lymph nodes (p < 0.001) was related to non-curable operations. The mean standard uptake value (SUV) of primary tumors of patients who underwent non-curable operations was significantly higher than that of patients with curable operations (p = 0.001). When the SUV was greater than 5 and FDG uptake of LN was positive, non-curable operations were predicted with a sensitivity of 35.2%, a specificity of 91.0% and an accuracy of 76.7%. Conclusions High SUV of the primary tumor and positive FDG uptake in local lymph nodes at PET/CT could predict non-curative resection in locally advanced gastric cancer. Therefore, information from preoperative PET/CT can help physician decisions regarding other modalities without laparotomy.

We appreciate the comments by Drs. Bali, Roukos, and Dr. Ziogas regarding our recently published article in the Annals of Surgical Oncology. To date, there have been no definite diagnostic methods established for recurrent gastric cancer, and recurrence has mostly been diagnosed using a combinatory analysis of several methods including computed tomography (CT), positron emission tomography (PET), tumor marker evaluation, and even diagnostic laparoscopy. Of these, CT has been the most popular method for detecting recurrent gastric cancer without invasiveness, although several reports have shown that CT is not specific for diagnosing recurrent tumors following curative gastric cancer surgery. However, our results indicated that CT is an essential follow-up method. Additional studies such as PET-CT or tumor marker identification require more clinical studies of their diagnostic accuracy and costeffectiveness before they can be established as follow-up methods. Based on our survey, follow-up studies after curative gastric cancer surgery are performed every 3 to 12 months with a physical examination and imaging methods in Korea. However, a consensus has not been reached for the optimal frequency of follow-up studies. Although patients with recurrent gastric cancer have poor outcomes, their prognoses have been improved using state-of-the-art treatments, such as new chemotherapeutic agents and molecular target therapy. Specifically, our previous study showed that complete resection of the metastatic lesion could lead to a better prognosis than other treatments. Therefore, early detection of recurrence by intensive follow-up can be meaningful. In addition, meta-analysis results of the cost effectiveness of follow-up studies after curative colorectal cancer surgery have revealed that intensive follow-up schedules were economically justified in the United Kingdom. However, there have been no studies performed to evaluate those after gastric cancer surgery. Randomized controlled clinical trials (RCTs) are needed to identify follow-up schedules that are optimal for patient survival and cost effectiveness between conventional and intensive follow-up strategies. In the future, extensive and intensive follow-up studies after curative gastric cancer surgery will be used according to the stage of the patient. Searching for gene mutations and tissue biomarkers may help to decide how extensive and intensive the follow-up studies should be to improve the prognosis of patients with recurrent gastric cancer. However, those issues should be discussed after routine follow-up schedules are established through additional clinical studies and well-designed randomized controlled clinical trials.