A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Feasibility of laparoscopic gastrectomy for patients with poor physical status: a retrospective cohort study based on a nationwide registry database in Japan.

BACKGROUND: Laparoscopic gastrectomy (LG) is an established minimally invasive procedure for gastric cancer. However, it is controversial whether LG is useful for patients with poor physical status classified into higher classes of the American Society of Anesthesiologists physical status (ASA-PS) classification. The aim of this study was to determine the feasibility of LG in patients with ASA-PS class ≥ 3. METHODS: We extracted data for a total of 28,160 patients with an ASA-PS class ≥ 3 who underwent distal or total gastrectomy for gastric cancer between January 2013 and December 2017 from the National Clinical Database Japan society for gastroenterological surgery registry. We developed a propensity score model from baseline demographics and comorbidities and matched patients undergoing LG to those undergoing open gastrectomy (OG) using a 1:1 ratio. Mortality and morbidities (within 30 days and in-hospital) were compared between the 6998 matched patient pairs. RESULTS: In-hospital mortality was significantly lower in patients undergoing LG than in those undergoing OG (2.3% vs. 3.0%, p = 0.01), while the 30-day mortality was similar (1.6% vs. 1.5%). The length of hospital stay was significantly shorter in the LG group (median, 14 days vs. 17 days, p < 0.001). The LG group had a significantly lower incidence of postoperative complications in patients with any grade complication (20.3% vs. 22.5%, p = 0.002) as well as those with ≥ grade 3 complications (8.7% vs. 9.8%, p = 0.03). CONCLUSION: LG was associated with decreased in-hospital mortality and a lower incidence of several postoperative complications when compared to OG among patients with poor physical condition.

Asymmetric dimethylation at histone H3 arginine 2 by PRMT6 in gastric cancer progression.

Histone modification plays important molecular roles in development and progression of cancers. Dysregulation of histone H3 arginine (R) methylation is still unknown in primary cancer, including gastric cancer (GC). Although PRMT6 contributes to asymmetric dimethylation at H3R2 (H3R2me2as) in cancer cells, its molecular functions are poorly understood in GC. In this study, we assessed H3R2me2as and PRMT6 expression levels in 133 primary GC tissues by immunohistochemistry. Increased H3R2me2as was found in 68 GC (51.1%) cases and independently related to poor prognosis. PRMT6 was overexpressed in 70 GC (52.6%) and strongly correlated with the global H3R2me2as levels (P < 0.001). By analyzing biological functions of PRMT6 in GC cell lines by lentivirus-based systems, PRMT6 overexpression enhanced global H3R2me2as and invasiveness in vitro, while PRMT6 knockout (PRMT6-KO) suppressed these effects and tumorigenicity in vivo. ChIP and microarray assays demonstrated that PRMT6-KO GC cells decreased the enrichments of H3R2me2as at the promoter regions of PCDH7, SCD and IGFBP5, resulting in upregulation of their gene expression. PRMT6 was recruited to the promoter regions of PCDH7 and SCD in the PRMT6-overexpressed cells. Knockdown of tumor suppressor PCDH7 in the PRMT6-KO GC cells elevated cell migration and invasion. PRMT6 expression inversely correlated with PCDH7 expression in primary GC (P = 0.021). Collectively, our findings strongly indicate that H3R2me2as is a strong prognostic indicator of GC patients, and PRMT6-overexpressing GC cells may acquire invasiveness through direct transcriptional inhibition of PCDH7 by increasing H3R2me2as level. Thus, inhibition of the PRMT6-H3R2me2as pathway could be a promising new therapeutic strategy in GC.

Intraoperative Body Fluid Amylase as a Novel Indicator of Postgastrectomy Pancreatic Fistula.

BACKGROUND: Although many methods to prevent the development of postoperative pancreatic fistula (POPF) after gastrectomy have been reported, POPF can only be identified after it has occurred. Various therapeutic measures could be taken if signs of POPF could be detected intraoperatively. METHODS: We conducted a prospective study in which we attempted to predict POPF by measuring the intraoperative amylase concentration in the peripancreatic body fluid. To collect the body fluid, three sponges were placed around the pancreas at lymph node station Nos. 6, 8, and 11 during lymphadenectomy. The amylase concentration was measured in the body fluid squeezed from the sponges. We investigated whether the intraoperative body fluid amylase concentration (IBAC) was associated with POPF formation. RESULTS: In total, 109 patients were enrolled from February 2016 to March 2018, and we analyzed 81 eligible patients. Clavien-Dindo grade ≥ II POPF occurred in eight patients (9%). The IBAC was significantly higher in sponges No. 6 (P = 0.044) and No. 8 (P = 0.007). The incidence of POPF was predicted by using an IBAC cutoff value for No. 6 (1047 IU/L; sensitivity 87.5%; specificity 65.0%; positive likelihood ratio 2.5) and No. 8 (400 IU/L; sensitivity 87.5%; specificity 68.5%; positive likelihood value 2.8), respectively. The IBAC in sponge No. 11 tended to be higher (P = 0.054). CONCLUSIONS: By measuring the IBAC, surgeons might predict POPF easily and noninvasively during surgery. This method is one of the most effective ways to predict POPF intraoperatively.

Long-term outcomes of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG0703).

BACKGROUND: Laparoscopic gastrectomy has become a common surgical treatment for gastric cancer in eastern Asian countries. However, a large-scale prospective study to investigate the benefit of laparoscopy-assisted distal gastrectomy (LADG) regarding long-term outcomes has never been reported. We have already reported the short-term outcomes of this study. Here we report long-term outcomes as the secondary endpoints of this study after a 5-year follow-up period. METHODS: This study comprised patients with clinical stage I gastric cancer who were able to undergo a distal gastrectomy. LADG with D1 plus suprapancreatic lymph node dissection was performed by credentialed gastric surgeons who had each conducted at least 30 LADG and 30 open gastrectomy procedures. The primary endpoint was the proportion of patients who developed either anastomotic leakage or pancreatic fistula. The secondary endpoints included overall survival and relapse-free survival. RESULTS: From November 2007 to September 2008, 176 eligible patients were enrolled, comprising 140 patients with pathological stage IA disease, 23 patients with pathological stage IB disease, 9 patients with pathological stage II disease, and 4 patients with pathological stage IIIA disease. No patients had recurrent disease, and three of the patients died within the follow-up period. The 5-year overall survival was 98.2% (95% confidence interval 94.4-99.4%) and the 5-year relapse-free survival was 98.2% (95% confidence interval 94.4-99.4%). CONCLUSIONS: The long-term outcomes of stage I gastric cancer patients undergoing LADG seem comparable to those of patients undergoing an open procedure, although this result should be confirmed by a randomized control trial. We have already completed accrual of 921 patients for a multicenter randomized phase III trial (JCOG0912) to confirm the noninferiority of LADG compared with open gastrectomy in terms of relapse-free survival.

Long- and short-term outcomes of laparoscopic gastrectomy versus open gastrectomy in patients with clinically and pathological locally advanced gastric cancer: a propensity-score matching analysis.

BACKGROUND: Laparoscopic (laparoscopy-assisted) gastrectomy (LG) has several short-term benefits as compared with open distal gastrectomy (OG) in patients with advanced gastric cancer (AGC). Survival rates did not differ significantly between LG and OG in retrospective studies of AGC, although some studies included unmatched groups of patients or patients with AGC who had a preoperative diagnosis of early gastric cancer. The aim of present study was to compare the short- and long-term outcomes of patients with AGC who underwent LG with those of patients with AGC who underwent OG using a propensity-score matching analysis. METHODS: The study group comprised patients with a preoperative and pathologically confirmed diagnosis of AGC who underwent LG or OG with lymphadenectomy between January 2001 and December 2012 in our hospital. To minimize bias between the LG and OG groups, propensity scores were calculated using a logistic regression model and the following variables: sex, age, body-mass index, American Society of Anesthesiologists physical status class, type of gastrectomy, and clinical and pathological tumor stage. After propensity-score matching, 104 patients (52 who underwent LG and 52 who underwent OG) were studied. RESULTS: LG was associated with significantly earlier initiation of food intake (p <0.01) and a significantly shorter period of postoperative hospitalization (p <0.01). The incidence of all-grade overall, surgical, and medical complications did not differ significantly between the LG group and OG group (p = 0.24, p = 0.12, and p >0.99). Overall and relapse-free survival also did not differ between the LG group and OG group (p = 0.96, p = 0.91). In each tumor stage, overall and relapse-free survival did not differ significantly between the LG group and OG group. CONCLUSION: LG can be a feasible treatment that is beneficial in terms of earlier recovery after operation and can be expected to result in similar survival as OG in patients with AGC.

Long-term functional outcomes of Roux-en-Y versus Billroth I reconstructions after laparoscopic distal gastrectomy for gastric cancer: a propensity-score matching analysis.

BACKGROUND: Only a few reports discuss long-term functional outcomes and changes observed in patients over several years following a distal gastrectomy. We investigated long-term functional outcomes and changes after laparoscopic distal gastrectomy based on the analysis of postoperative conditions and endoscopic findings observed in patients. METHODS: The study group comprised 159 patients who underwent Roux-en-Y reconstruction following laparoscopic distal gastrectomy (R-Y group) between December 2008 and November 2012 and 78 patients who underwent Billroth I reconstruction (B-I group) between January 2002 and November 2012. To minimize bias between the two groups, propensity scores were calculated using a logistic regression model. The groups were compared with respect to postoperative conditions and endoscopic findings at 1, 3, and 5 years postoperatively. RESULTS: The B-I group demonstrated more frequent heartburn than the R-Y group at 3 and 5 years postoperatively. No significant differences were found in terms of loss of body weight and food intake. Endoscopic findings showed significantly lesser residual food and remnant gastritis in the R-Y group at each annual postoperative follow-up. The incidence of bile reflux and reflux esophagitis in the B-I group gradually increased over the years and showed a significant difference at the culmination of the 5-year postoperative follow-up, compared to the R-Y group. CONCLUSIONS: Roux-en-Y reconstruction was superior to Billroth I reconstruction in terms of frequency of occurrence of residual food, bile reflux, remnant gastritis, and reflux esophagitis in the long term. Differences between the two methods became more evident as the follow-up period lengthened.

[Robotic-Assisted Surgery - Current State of the Art and Future Perspective Colorectal Cancer].

Interest in minimally invasive surgery has increased in recent decades. Robotic-assisted laparoscopic surgery(RALS)was introduced as the latest advancement in minimally invasive surgery. RALS has the potential to provide better clinical outcomes in rectal cancer surgery, allowing for precise dissection in the narrow pelvic space. In addition, RALS represents an important advancement in surgical education with respect to use of the dual-console robotic surgery system. Because the public health insurance systems in Japan have covered the cost of RALS for rectal cancer since April 2018, RALS has been attracting increasingly more attention. Although no overall robust evidence has yet shown that RALS is superior to laparoscopic or open surgery, the current evidence supports the notion that technically demanding subgroups(patients with obesity, male patients, and patients treated by extended procedures)may benefit from RALS. Technological innovation is a constantly evolving field. Several companies have been developing new robotic systems that incorporate new technology. This competition among companies in the development of such systems is anticipated to lead to further improvements in patient outcomes as well as drive down the cost of RALS, which is one main concern of this new technique.

[Two Cases of Rectal Cancer with Pelvic Local Recurrence Complicated with Sepsis after Rectal Cancer Surgery Successfully Treated with Radiation Therapy].

Treatment of rectal cancer with postoperative pelvic recurrence may complicate infection and may be difficult to treat. We experienced 2 cases complicated with sepsis due to infection in the pelvic local recurrence in which radiation therapy was performed and they were shifted to outpatient molecular-targeted drug therapy. Case 1 involved a 58-year-old woman. In December 2011, colostomy and chemotherapy were performed for locally advanced rectal cancer. In June 2012, we performed low anterior resection. In January 2014, chemotherapy was started for pelvic recurrence. She discontinued treatment for 4 months due to personal circumstances. Recurrence was worsened, and infection caused sepsis and she was admitted to the hospital in February 2017. Infection was not improved with antibiotic drugs, and radiation therapy(60 Gy/30 times)was performed. Infection was improved, and panitumumab monotherapy was started and she was discharged. Case 2 involved a 61-year-old man. In February 2014, a lower anterior resection for rectal cancer was performed. In September 2015, chemotherapy was started for pelvic recurrence. In November 2016, chemotherapy was discontinued due to esophageal variceal rupture. Recurrence was worsened, and infection caused sepsis and he was admitted to the hospital in May 2017. Radiation therapy(50 Gy/20 times)was performed after colostomy. Infection was improved, and cetuximab monotherapy was started and he was discharged.

Double-tract reconstruction after laparoscopic proximal gastrectomy using detachable ENDO-PSD.

BACKGROUND: Proximal gastrectomy (PG) is widely performed in Japan as a function-preserving surgical approach. Since esophagogastrostomy (EG) was associated with increased reflux symptoms and anastomotic strictures, we have chosen double-tract reconstruction (DTR) as the standard reconstruction method since March 2013. In this study, we described a novel method of laparoscopic DTR using detachable ENDO-PSD and compared its 1-year outcome with EG performed formerly in our institution. METHODS: Patients who underwent laparoscopic PG between May 2005 and July 2014 were retrospectively divided into two groups based on the type of reconstruction and were subsequently analyzed (19 patients in the DTR group and 22 in the EG group). All of them underwent a laparoscopic PG with regional lymph node dissection. In the DTR group, the lower left port site was extended to 4 cm, and an intracorporeal purse-string suture was performed using the detachable ENDO-PSD. The jejunogastrostomy was fashioned on the anterior side of the remnant stomach parallel to the transection line, 2 cm from the cut end. The EG group used the conventional purse-string suture instrument through the 6 cm upper midline mini-laparotomy incision. Patient characteristics, operative data, early operative complications and 1-year postoperative follow-up findings were compared between the two groups. RESULTS: The frequencies of reflux symptoms (10.5 vs. 54.5%, P = 0.003), usage of proton pump inhibitors (31.6 vs. 72.7%, P = 0.008), and anastomotic strictures (0 vs. 27%, P = 0.014) were significantly lower in the DTR group as compared to the EG group. There were no significant differences between the two groups with regard to operation time, blood loss, postoperative hospital stay, postoperative complications, average postoperative/preoperative weight loss ratio, and postoperative/preoperative ratio of biochemical markers (hemoglobin, total protein, albumin, cholesterol). CONCLUSION: Our results indicate that DTR is a useful reconstruction method after PG, especially in terms of preventing reflux esophagitis and anastomotic strictures.

Esophagojejunostomy Using the Purse-String Suturing Device After Laparoscopic Total or Proximal Gastrectomy for Gastric Cancer.

BACKGROUND: Performing a safe esophagojejunostomy is important for the standardization of laparoscopic total gastrectomy. We have performed intracorporeal esophagojejunostomy by a circular stapler using the purse-string suturing device that we co-developed. The advantage of this device is that it makes use of the same surgical procedure as open surgery, but it does not depend on the surgeon's technical skills since this device does not require the laparoscopic hand-sewn technique. Furthermore, we have also adapted this device for double-tract reconstruction after laparoscopic proximal gastrectomy. In this study, we present the surgical procedures and postoperative short-term outcomes that were obtained using this novel technique. METHODS: We enrolled 94 patients that underwent intracorporeal esophagojejunostomy by circular stapler using our device after laparoscopic total or proximal gastrectomy for gastric cancer between November 2009 and October 2016. RESULTS: Postoperative complications related to esophagojejunostomy were due to anastomotic stenosis in two cases (2.1%) and leakage of the jejunum stump in one case (1.1%). CONCLUSIONS: Intracorporeal esophagojejunostomy by circular stapler using the purse-string suturing device is safe and feasible. This method can be one of the standard procedures for performing intracorporeal esophagojejunostomy.

Risk Factor of Pancreatic Fistula after Radical Gastrectomy from the Viewpoint of Fatty Pancreas.

BACKGROUND: We suspected that fatty pancreas, accompanied with metabolic syndrome, may be associated with the incidence of postoperative pancreatic fistula (POPF) after radial gastrectomy. METHODS: Between February 2012 and March 2014, we reviewed consecutive 79 gastric cancer patients who underwent radical gastrectomy. To quantify the degree of fatty infiltration to pancreas by preoperative contrast-enhanced CT, we measured ratios and differences between pancreatic and splenic attenuation values (P/S and P-S, respectively). The optimal cut-off values of P/S and P-S for predicting POPF were determined using the receiver operating characteristic (ROC) curve analysis. Risk factors for POPF of International Study Group on Pancreatic Fistula grade B or higher were examined using univariate and multivariate analyses. RESULTS: POPF occurred in 6 patients (7.6%). ROC curve analyses revealed that the most optimal predictive values of P/S and P-S were 0.74 and -28.8, respectively. Univariate analysis demonstrated that high visceral fat area (p = 0.037), low P/S (p = 0.013), and low P-S (p = 0.006) were significant risk factors of POPF. Multivariate analysis demonstrated that low P/S (OR 10.2 [p = 0.046]) and low P-S (OR 13.2 [p = 0.023]) were significant risk factors of POPF. CONCLUSION: Fatty pancreas is a risk factor of POPF after radical gastrectomy.

High expression of EphA3 (erythropoietin-producing hepatocellular A3) in gastric cancer is associated with metastasis and poor survival.

BACKGROUND: As the major subfamily of receptor tyrosine, erythropoietin-producing hepatocellular (Eph) receptor has been related to progression and prognosis in different types of tumors. However, the role and mechanism of EPHA3 in gastric cancer is still not well understood. METHODS: Specimen were collected from 202 patients who underwent gastric resection for gastric adenocarcinoma. The expression of EphA3 was studied using immunohistochemistry. We analyzed the clinicopathological factors and prognostic relevance of EphA3 expression in gastric cancer. RESULTS: High expression of EphA3 was associated with male predominance (p = 0.031), differentiated histology (p < 0.001), depth of tumor (p = 0.002), lymph node metastasis (p = 0.001), distant metastasis (p = 0.021), liver metastasis (p = 0.024), advanced stage (p < 0.001), and high HER2 expression (p = 0.017). Relapse-free survival (RFS) was significantly worse in patients with high expression of EphA3 than in those with low expression of EphA3 (p = 0.014). Multivariate analysis for RFS showed that depth of tumor [hazard ratio (HR) 9.333, 95% confidence interval (CI) 2.183-39.911, p = 0.003] and lymph node metastasis [hazard ratio (HR) 5.734, 95% confidence interval (CI) 2.349-13.997, p < 0.001] were independent prognostic factors. CONCLUSIONS: These findings suggest that high expression EphA3 may participate in metastasis and worse survival.

Different clinical significance of FGFR1-4 expression between diffuse-type and intestinal-type gastric cancer.

BACKGROUND: Receptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1-4 expression separately in DGC and IGC. METHODS: Tumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution. The expression levels of FGFR1, 2, 3, and 4 were measured in the tumors by immunohistochemical analysis. RESULTS: In DGC, high expression of FGFR1, FGFR2, or FGFR4 was significantly associated with the depth of invasion, lymph-node metastasis, pathological stage, and distant metastasis or recurrent disease. Patients with high expression of FGFR1, FGFR2, or FGFR4 had significantly poorer disease-specific survival (DSS) (p = 0.009, p = 0.001, and p = 0.023, respectively). In IGC, only FGFR4 expression was significantly associated with factors relative to tumor progression and with shorter DSS (p = 0.012). CONCLUSION: In conclusion, high FGFR4 expression correlated with tumor progression and survival in both DGC and IGC, whereas high expression of FGFR1 and 2 correlated with tumor progression and survival in only DGC.

TPX2 expression is associated with poor survival in gastric cancer.

BACKGROUND: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis. METHODS: Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues. RESULTS: The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013). CONCLUSIONS: Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.

q-space MR imaging of gastric carcinoma ex vivo: Correlation with histopathologic findings.

PURPOSE: The purpose of this study was to establish the feasibility of q-space imaging (QSI) as a method of assessing the depth of mural invasion, histologic grade, and the presence of lymph node metastasis in gastric carcinomas. METHODS: A 7.0 Tesla MR imaging system was used to investigate 20 gastric specimens containing a carcinoma. QSI was performed by using the following parameters: 50-60 mm × 25-30 mm field of view, 2-mm section thickness, 256 × 128 matrix, 10 b values in the 0-7163 s/mm(2) range, which corresponded to q values of 0-1026/cm, and motion-probing gradients perpendicular to the gastric wall. The MR images and the histopathologic findings were then compared. RESULTS: The depth of tumor invasion of the gastric wall in all 20 carcinomas (100%) was established by using mean displacement, zero-displacement probability, and kurtosis maps. The QSI parameters were significantly correlated with the histologic grades of the gastric carcinomas (all P < 0.001). The QSI parameters made it possible to differentiate between metastatic and nonmetastatic lymph nodes (all P = 0.001). CONCLUSION: Ex vivo QSI facilitates excellent diagnostics for evaluating gastric carcinomas in terms of mural invasion, histologic grade, and the presence of lymph node metastasis. Magn Reson Med 76:602-612, 2016. © 2015 Wiley Periodicals, Inc.

[A Case of a-Fetoprotein Producing Gastric Cancer with Lymph Node Recurrence after Endoscopic Submucosal Dissection].

A 70-year-old man underwent endoscopic submucosal dissection(ESD)for 2 early-stage gastric cancers in 2009 and 2014, respectively. Both were pathologically diagnosed after curative resection. In 2015, we detected swollen lymph nodes in the lesser curvature of the stomach on computed tomography(CT). PET-CT revealed that the swollen lymph nodes showed an abnormal uptake of fluorodeoxyglucose; therefore, we considered the possibility of metastatic recurrence of the gastric can- cer. The patient's serum a-fetoprotein(AFP)level was elevated to 30.6 ng/mL. The intraoperative pathological diagnosis of the swollen lymph node was tub2. We diagnosed this case as metastatic recurrence of gastric cancer and performed distal gastrectomy with lymph node dissection. Metastases were found in 3 of the resected lymph nodes. Immunohistochemical staining for AFP was positive in the specimens obtained via ESD in 2014 and in the metastatic lymph nodes. We diagnosed the patient with AFP-producing gastric cancer. On additional trimming of the specimen obtained via ESD in 2014, we found slight lymphatic invasion.

Gastric Carcinoma: Ex Vivo MR Imaging at 7.0 T-Correlation with Histopathologic Findings.

PURPOSE: To determine the imaging detail and diagnostic information that can be obtained at 7.0-T magnetic resonance (MR) imaging with a voxel volume of 9.5-14.0 nL as a means of evaluating the depth of mural invasion by gastric carcinomas ex vivo. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained from each patient. Twenty gastric specimens containing 20 carcinomas were studied with a 7.0-T MR imaging system equipped with a four-channel surface coil. MR images were obtained with a 50-60 × 25-30 mm field of view, a 512 × 256 matrix, and a 1.0-mm section thickness, resulting in a voxel volume of 0.0095-0.0140 mm(3) (9.5-14.0 nL). The signal intensity of the gastric wall layers, tumor tissue, and fibrosis was described as low, intermediate, or high by comparing it with the signal intensity of the muscularis propria. Depth of invasion initially was assessed by two reviewers independently and then by the two reviewers in consensus. MR images were compared with histopathologic findings. RESULTS: The 7.0-T T2-weighted MR images clearly depicted the normal gastric wall in all 20 specimens (100%) as consisting of seven layers, which clearly corresponded to the tissue layers of the gastric wall. These MR images enabled clear differentiation between tumor tissue and fibrosis. Reviewers disagreed on the depth of invasion at the initial reading in three (15%) of 20 specimens (between mucosa and submucosa in two specimens and between muscularis propria and subserosa and serosa in one specimen); however, in all 20 gastric carcinomas, the depth of invasion could be accurately determined on T2-weighted images after consensus interpretation. CONCLUSION: Ex vivo 7.0-T MR imaging enables clear delineation of the gastric wall layers and clear differentiation of tumor tissue from fibrosis and allows one to assess the depth of mural invasion by gastric carcinomas.

Erythropoietin-Producing Hepatocellular A1 is an Independent Prognostic Factor for Gastric Cancer.

BACKGROUND: Erythropoietin-producing hepatocellular (Eph) receptors are the largest subfamily of receptor tyrosine kinases that have been investigated as a possible target for molecular targeted therapy of various cancers. METHODS: Patients (n = 222) who underwent gastrectomy for primary gastric cancer were enrolled in this study. Tumor protein expression of EphA1 and EphB6 in surgically resected specimen was investigated using immunohistochemistry. The associations between expression of EphA1 and EphB6 and clinicopathological factors and prognosis were analyzed. RESULTS: High expression of EphA1 was associated with undifferentiated histology (P = 0.002), depth of tumor (P < 0.001), lymph node metastasis (P = 0.001), venous invasion (P = 0.015), stage (P = 0.001), and remote metastasis or recurrence (P < 0.001). In univariate analysis, patients with high expression of EphA1 had significantly poorer overall survival and relapse-free survival compared with patients with low EphA1 expression. The expression level of EphB6 was not associated with any clinicopathological factors and patient survival. Multivariate analysis indicated that depth of tumor [hazard ratio (HR) 9.26, 95 % confidence interval (CI) 0.03-0.46, P = 0.003], lymph node metastasis (HR 9.26, 95 % CI 0.07-0.39, P < 0.001), and high expression of EphA1 (HR 1.86, 95 % CI 0.29-0.99, P = 0.048) are independent prognostic factors for relapse-free survival. CONCLUSIONS: EphA1 is a possible target of molecular targeted therapy of gastric cancer.