Serum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment.

OBJECTIVE: The mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans. The aim of this study was to evaluate the mechanisms underlying serum glucose excretion in the small intestine and its contribution to glucose homeostasis after bariatric surgery. DESIGN: 2-Deoxy-2-[18F]-fluoro-D-glucose (FDG) was measured in RYGB-operated or sham-operated obese diabetic rats. Altered glucose metabolism was targeted and RNA sequencing was performed in areas of high or low FDG uptake in the ileum or common limb. Intestinal glucose metabolism and excretion were confirmed using 14C-glucose and FDG. Increased glucose metabolism was evaluated in IEC-18 cells and mouse intestinal organoids. Obese or ob/ob mice were treated with amphiregulin (AREG) to correlate intestinal glycolysis changes with changes in serum glucose homeostasis. RESULTS: The AREG/EGFR/mTOR/AKT/GLUT1 signal transduction pathway was activated in areas of increased glycolysis and intestinal glucose excretion in RYGB-operated rats. Intraluminal GLUT1 inhibitor administration offset improved glucose homeostasis in RYGB-operated rats. AREG-induced signal transduction pathway was confirmed using IEC-18 cells and mouse organoids, resulting in a greater capacity for glucose uptake via GLUT1 overexpression and sequestration in apical and basolateral membranes. Systemic and local AREG administration increased GLUT1 expression and small intestinal membrane translocation and prevented hyperglycaemic exacerbation. CONCLUSION: Bariatric surgery or AREG administration induces apical and basolateral membrane GLUT1 expression in the small intestinal enterocytes, resulting in increased serum glucose excretion in the gut lumen. Our findings suggest a novel, potentially targetable glucose homeostatic mechanism in the small intestine.

Real-time identification of aberrant left hepatic arterial territories using near-infrared fluorescence with indocyanine green during gastrectomy for gastric cancer.

BACKGROUND: An aberrant left hepatic artery is frequently encountered during upper gastrointestinal surgery, and researchers have yet to propose optimal strategies with which to address this arterial variation. The objective of this study was to determine whether the areas perfused by an aberrant left hepatic artery can be visualized in real-time using near-infrared fluorescence imaging with indocyanine green. METHODS: Patients with gastric adenocarcinoma who underwent minimally invasive radical gastrectomy from May 2018 to August 2019 were enrolled and retrospectively analyzed at a single-center. Patients with an aberrant left hepatic artery and normal preoperative liver function were examined. After the clamping of an aberrant left hepatic artery, indocyanine green was administered via a peripheral intravenous route during surgery. Fluorescence at the liver was visualized under near-infrared fluorescence imaging. RESULTS: In 31 patients with aberrant left hepatic arteries, near-infrared fluorescence imaging was used without adverse events associated with indocyanine green. Six (19%) patients were reported to have an aberrant left hepatic artery upon preoperative CT imaging, while all other instances were detected during surgery. Fluorescence excitation on the liver was, on average, visible after 43 s (range, 25-65). Fluorescence across the entire surface of the liver was noted in 20 (65%) patients in whom the aberrant left hepatic artery could be ligated. Aberrant left hepatic arteries were safely preserved in 10 (32%) patients who showed areas of no or partial fluorescence excitation. Guided by near-infrared fluorescence imaging, ligation of aberrant left hepatic arteries elicited no significant changes in postoperative liver function. CONCLUSION: Near-infrared fluorescence imaging facilitates the identification of aberrant left hepatic arterial territories, guiding decisions on the preservation or ligation of this arterial variation.

Effect of histologic differences between biopsy and final resection on treatment outcomes in early gastric cancer.

BACKGROUND AND STUDY AIMS: Biopsy-based histologic diagnosis is important in determining the treatment strategy for early gastric cancer (EGC). However, there are few studies on how histologic discrepancy may affect patients' treatment outcomes. We aimed to investigate the impact of histopathologic differences between biopsy and final specimens from endoscopic resection (ER) or gastrectomy on treatment outcomes in patients with EGC. We also examined the predictive factors of histologic discrepancy. PATIENTS AND METHODS: We analyzed the data of 1851 patients with EGC treated with ER or gastrectomy. We compared the histology between biopsies and final resected specimens from ER or gastrectomy. We also examined changes in treatment outcomes according to histologic differences. RESULTS: Histologic discrepancy was observed in 11.9% of patients in the ER group and 10.7% of those in the gastrectomy group. In patients treated with ER who showed histologic discrepancy, 80.9% showed differentiated-type EGC (D-EGC) on biopsy but undifferentiated-type-EGC (UD-EGC) after ER, of which 78.9% were non-curative resection. In patients treated with gastrectomy who showed histologic discrepancy, 39% showed UD-EGC on biopsy but showed D-EGC after gastrectomy. A total of these patients had absolute and expanded indications for ER. Moderately differentiated and poorly differentiated adenocarcinoma on biopsy were predictive factors of histologic discrepancy in UD-EGC and D-EGC on final resection, respectively. CONCLUSIONS: About 10% of patients showed histologic discrepancy between biopsy and final resection with ER or gastrectomy. Histologic discrepancy can affect treatment outcomes, such as non-curative resection in ER or missing the opportunity for ER in gastrectomy.

Multi-institutional validation of the 8th AJCC TNM staging system for gastric cancer: Analysis of survival data from high-volume Eastern centers and the SEER database.

BACKGROUND: The clinical relevance and general applicability of the 8th American Joint Committee on Cancer TNM gastric cancer staging system vs the 7th version have not been examined using datasets from both the East and West. METHODS: Patients (n = 29 984) treated for gastric adenocarcinoma at two high-volume centers (Severance Hospital [SH] and Gangnam Severance Hospital [GSH]) in Korea and data from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Survival curves, the performance of tumor staging, and the homogeneity of modified subgroups were compared. RESULTS: Minute changes were noted in the stage IIB subgroup; most changes were noted in stage III. Applying the 8th staging system facilitated better prediction of survival than applying the 7th version for SH data according to the log-rank test, C-index, and AIC (8444.5 vs 9263.8, 0.796 vs 0.798, and 104152 vs 103909, respectively). Its performance was also superior for GSH and SEER data. In a subgroup analysis of stages IIB to IIIC in SH, GSH, and SEER data, the 8th staging system showed similar or more homogeneous survival for each sub-classification than the 7th version. CONCLUSION: Compared with the 7th gastric cancer staging system, the newer version more accurately predicted prognosis and stratified subgroups more homogeneously.

Skip lymph node metastasis in gastric cancer: is it skipping or skipped?

BACKGROUND: Skip metastasis is the presence of a metastatic lymph node (LN) in an extraperigastric (EP) area without perigastric (PG) involvement. The mechanism and prognosis of skip metastasis are still unknown. The purpose of this study was to scrutinize the clinical significance of skip metastasis in gastric cancer. METHODS: Data were reviewed from 6,025 patients who had undergone gastrectomy for primary gastric cancer. Patients were categorized as a PG-only group when the metastatic LNs were limited to only the PG area, as a PG + EP group if metastatic LNs extended to both the PG area and the EP area, and as a skip group if metastatic LNs were in the EP area but there were no metastatic LNs in the PG area. RESULTS: After we had performed matching, the prognosis of the skip group was worse than that of the PG-only group (adjusted hazard ratio 1.69, 95% confidence interval 1.13-2.54) and was similar to that of the PG + EP group (adjusted hazard ratio: 1.54, 95% confidence interval 0.92-2.59). The number of retrieved LNs was less in the skip group than in the other groups, especially from the PG area (p < 0.001). CONCLUSIONS: The prognosis of the skip group was worse than that of the PG-only group and was similar to that of the PG + EP group when the tumor stage was considered. It is difficult to conclude whether skip metastasis is real skipping of cancer cells or a result of inadequate LN sampling. Further evaluation of LNs in the PG area of the skip group could provide more clues for the mechanism of skip metastasis.

Liver-directed treatments for liver metastasis from gastric adenocarcinoma: comparison between liver resection and radiofrequency ablation.

BACKGROUND: Although various liver-directed treatment modalities, such as liver resection and radiofrequency ablation (RFA), have been applied to treat liver metastases from gastric cancer, optimal management of them remains controversial. In patients with liver metastasis from gastric cancer, we investigated the short- and long-term outcomes of liver resection and RFA and analyzed factors influencing survival. METHODS: A total of 98 gastric cancer patients with liver metastasis and no extrahepatic disease were treated by liver resection (n = 68) or RFA (n = 30). Short- and long-term outcomes were evaluated retrospectively for each of the liver-directed treatments. RESULTS: Severe complication rates did not differ between liver resection (18 %) and RFA (10 %) (p = 0.333). Only one treatment-related mortality occurred in the liver resection group. No statistically significant difference in survival was noted between the treatment groups. Median overall survival after liver resection was 24 months, with 3-year overall and progression-free survival rates of 40.6 % and 30.4 %, respectively. Median overall survival after RFA was 23 months, with 3-year overall and progression-free survival rates of 43.0 % and 37.4 %, respectively. Only the size of the metastases was shown to be an independent prognostic factor for gastric cancer patients with liver metastasis. CONCLUSIONS: In select patients with liver metastasis from gastric cancer, liver resection and RFA showed satisfactory and comparable short- and long-term results. Thus, systemic chemotherapy may not be the only therapeutic option for patients with liver metastasis, and possible liver-directed treatment options for such patients should be considered on an individual basis.

Roux-en-Y gastric bypass stimulates hypothalamic miR-122 and inhibits cardiac and hepatic miR-122 expressions.

BACKGROUND: MicroRNAs (miRNAs) are endogenous noncoding small ribonucleic acids that have emerged as one of the central players of gene expression regulation. This study was designed to determine and identify miRNAs that are associated with Roux-en-Y gastric bypass (RYGB). METHODS: Male Sprague-Dawley rats were divided into two groups: sham and RYGB. Changes in food intake and body weight were measured. miRNA microarray analyses on the brain hypothalamus and heart were performed. The expressions of miR-122 were analyzed, and the activities of adenosine monophosphate-activated protein kinase (AMPK) were determined in the hypothalamus, heart, and liver. Antisense oligonucleotide miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo results. RESULTS: Body weights decreased in the RYGB group compared with those in sham group. Food intake was different between sham and RYGB groups. Of 350 miRNAs that were investigated, we observed that miR-122, being predominantly found in the liver, markedly increased (>35-fold) in the hypothalamus and decreased (>4-fold) in the heart. Quantitative polymerase chain reaction analysis revealed that expression of miR-122 was induced in hypothalamus but attenuated in the heart and liver of the RYGB group. Activities of AMPK were decreased in the hypothalamus but increased in the heart and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated phosphorylation levels AMPK. CONCLUSIONS: The results in this study suggest that RYGB regulates the expressions of miR-122 in the hypothalamus, heart, and liver, which in turn may modulate the activities of AMPK, the master regulator of metabolism.

Risk factors for complications during surgical treatment of remnant gastric cancer.

BACKGROUND: Surgical treatment for remnant gastric cancer is related to high mortality and morbidity. The aim of this study was to identify risk factors that predispose to postoperative complications after gastrectomy for remnant gastric cancer. METHODS: A total of 210 patients who underwent a gastrectomy for remnant gastric cancer between January 1998 and December 2012 were retrospectively analyzed. Surgical complications were reviewed and graded using the Clavien-Dindo classification. Univariate and multivariate analysis was performed to identify the risk factors for development of complications. RESULTS: The incidence of postoperative complications was 46% (96/210), and major complications occurred in 14% (30/210). The operation-related mortality rate was 1.0%. Multivariate analysis revealed that only a BMI ≥25 (P = 0.001) and blood transfusion (P < 0.001) were significant independent risk factors for major complication. Indication for the initial gastrectomy and previous anastomosis type were not related to the development of surgical complications. CONCLUSIONS: Although surgery for remnant gastric cancer is a complex procedure because of the previous operation, factors related to the previous operation do not affect the development of postoperative complications.

Minimally invasive surgery as a treatment option for gastric cancer in the elderly: comparison with open surgery for patients 80 years and older.

BACKGROUND: As life expectancy is increasing, the use of minimally invasive surgery (MIS) in the elderly is gaining interest. The aim of this study was to identify the impact of minimally invasive gastrectomy by comparing the procedure to open surgery in octogenarians. In addition, we also evaluated the role of gastrectomy in elderly gastric cancer patients by assessing long-term outcomes. METHODS: We retrospectively analyzed data from 99 gastric cancer patients aged 80 years or older, who underwent gastrectomy by either MIS or open surgery from 2005 to 2010. Patient characteristics, operative outcomes, pathologic results, morbidity, mortality, and follow-up data (including survival) were compared. RESULTS: Thirty patients underwent gastrectomy with MIS (19 laparoscopic and 11 robotic) and 69 patients underwent open gastrectomy. MIS demonstrated significantly less blood loss, lower analgesic consumption, faster time to first flatus and soft diet, and a shorter post-operative hospital stay. Multivariate analysis revealed that the type of operation had no effect on the occurrence of complications. There were two postoperative mortalities, both in the open group. Excluding these patients, the overall and disease-specific 5-year survival rates were 57.4 and 70.0 %, respectively. The overall (MIS 70.0 %; open 52.0 %) and disease-specific (MIS 81.8 %; open 65.1 %) 5-year survival rates were similar for the two groups. When we analyzed the 85 patients underwent curative resection only, the overall (MIS 71.4 %; open 58.4 %) and disease-specific (MIS 84.1 %; open 73.6 %) 5-year survival rates were similar for the two groups. CONCLUSIONS: MIS for gastric cancer may be performed safely and maintains the advantages of minimal invasiveness, even in extremely old patients. Furthermore, gastrectomy by either by MIS or open surgery can reduce gastric cancer-related deaths, even in patients 80 years or older.

Comparison of perioperative surgical outcomes between a bipolar device and an ultrasonic device during laparoscopic gastrectomy for gastric cancer.

BACKGROUND: The use of energy devices during laparoscopic gastrectomy for gastric cancer has increased as the frequency of laparoscopic surgery has increased. Our aim was to compare the perioperative surgical outcomes between using a bipolar device and an ultrasonic device during laparoscopic gastrectomy. METHODS: Retrospective review of a prospectively maintained database identified 186 patients who underwent laparoscopic gastrectomy performed by a single surgeon between November 2010 and August 2013. A bipolar device was used for 116 patients, and an ultrasonic device was used for 70 patients. Patient characteristics and perioperative surgical outcomes were compared between groups. RESULTS: Clinicopathologic characteristics were similar for both groups. The bipolar group had a significantly shorter operation time (154.9 vs. 167.8 min, p = 0.028) and higher rate of D2 lymph node dissection (29.3 vs. 15.7 %, p = 0.012). The bipolar device group experienced significantly less pain at 12 h [visual analog scale (VAS) pain score: 3.9 vs. 4.7, p = 0.027) and 18 h (VAS pain score: 3.5 vs. 4.1, p = 0.036) postoperatively. The bipolar group had earlier abdominal drain removal (p = 0.001) and a shorter hospital stay (p = 0.024). No significant differences in laboratory value changes, morbidity, or mortality were observed between the groups. CONCLUSION: Compared with the ultrasonic device, the bipolar device provided advantages in operation time, degree of postoperative pain, time of drain removal, and length of hospital stay. The bipolar device may be a useful and efficient energy device for laparoscopic gastrectomy. However, larger studies to confirm the safety of bipolar device during laparoscopic gastrectomy are warranted.

Is microsatellite instability a prognostic marker in gastric cancer? A systematic review with meta-analysis.

BACKGROUND AND OBJECTIVE: The relationship between survival in gastric cancer patients and the status of microsatellite instability (MSI) has not yet been established. The purpose of this meta-analysis was to obtain integrated and more precise data for the value of MSI as a prognostic marker in gastric cancer. METHODS: A comprehensive systematic review and meta-analysis were conducted using major electronic databases (PubMed, EMBASE, and the Cochrane Central) with keywords related to "microsatellite instability," "gastric cancer," and "prognosis." RESULTS: Twenty-four studies with 5,438 participants (712 cases were MSI gastric cancer) were included for pooling risk estimates of MSI in gastric cancer. Seventeen studies reported overall survival. The pooled hazard ratio (HR) for overall survival of MSI vs. non-MSI was 0.72 (95%CI: 0.59-0.88, P = .001) in a random-effects model. In the sensitivity analysis, the result from the most recent study showed the most heterogeneity. CONCLUSION: MSI gastric cancer was associated with good prognosis but there was heterogeneity in the recent studies. Changed epidemiology and effects of chemotherapy are potential causes of heterogeneity. Establishing a consensus for defining MSI in gastric cancer should be preferred for future studies.

Can we apply the same indication of endoscopic submucosal dissection for primary gastric cancer to remnant gastric cancer?

BACKGROUND: Currently, remnant gastric cancer (RGC) is uncommon compared with gastric stump cancer, but early detection of gastric cancer and improved postsurgical survival will lead to increased incidence of RGC. Therefore, the indication of endoscopic submucosal dissection (ESD) for RGC is now required, but there have been no reports about this because of the lack of information for RGC. METHODS: A retrospective review was conducted on 105 patients who underwent completion total gastrectomy (CTG) and 5 patients who underwent ESD for RGC between January 1998 and December 2010 at Yonsei University Hospital. RESULTS: Forty-one (39 %) of 105 patients were diagnosed with early RGC. Among these patients, 6 had an absolute indication for ESD, whereas 11 met expanded criteria for ESD. In these patients, there was no association between the severity of the former gastric cancer and the current RGC. Also, none of these 17 patients had LN metastasis after CTG, and only 1 (2.4 %) of 41 early RGC patients had LN metastasis. Median operative time was 216 min for CTG and median hospital stay was 8 days. There were two major and five minor complications. One splenectomy was performed because of injury that occurred during CTG. CONCLUSIONS: Applying the indication of ESD for primary gastric cancer to RGC would be possible, and it could be an alternative treatment option for selected patients with RGC.

Minimally invasive surgery for remnant gastric cancer: a comparison with open surgery.

BACKGROUND: Completion total gastrectomy for remnant gastric cancer (RGC) is technically challenging, especially using the minimally invasive approach. Only a few small case series have reported the technical feasibility of completion total gastrectomy by minimally invasive surgery (MIS). The aim of this study was to compare the efficacy and safety of MIS and open surgery for RGC. METHODS: We retrospectively analyzed 76 completion total gastrectomies for RGC between 2005 and 2012. Indications for MIS were limited to no evidence of serosa invasion or lymph node metastasis to extraperigastric areas on preoperative evaluation. We compared patient characteristics, intraoperative factors, post-operative outcomes, and survival for the MIS and open surgery groups. RESULTS: Eighteen patients underwent completion total gastrectomy with MIS (10 laparoscopic, 8 robotic) and 58 patients underwent open surgery. Operation time was longer in the MIS than the open group (266 vs. 203 min, P = 0.004), but the groups had similar estimated blood loss, frequency of unplanned other organ resection, and number of retrieved lymph nodes. The MIS group had a significantly earlier initiation of soft diet, shorter hospital stay, and fewer pain medication injections. Complication rates, recurrence, and overall 5-year survival were similar for the two groups. When we compared laparoscopy with robotic, similar result was shown in all parameters except operation time. CONCLUSIONS: Compared to open surgery, MIS for RGC demonstrated better short-term outcome and comparable oncologic results. MIS for RGC is feasible and safe and maintains advantages of minimal invasiveness. Both laparoscopic and robotic approaches are reasonable to the management of RGC.

Influence of psychological factors and pain sensitivity on the efficacy of opioid-free anesthesia: A randomized clinical trial.

OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).

A randomized controlled study to assess the effect of mosapride citrate on intestinal recovery following gastrectomy.

The enhanced recovery after surgery (ERAS) protocol, including prokinetic medications, is commonly used to prevent postoperative ileus. Prospective studies evaluating the effectiveness of mosapride citrate, a prokinetic 5-hydroxytryptamine 4 receptor agonist, in patients undergoing gastrectomy within the ERAS framework are lacking. This double-blind randomized trial included patients who were scheduled for laparoscopic or robotic gastrectomy for gastric cancer. Participants were randomly assigned to either a control (placebo) or experimental (mosapride citrate) group, with drugs administered on postoperative days 1-5. Bowel motility was evaluated based on bowel transit time measured using radiopaque markers, first-flatus time, and amount of food intake. No significant differences were observed in baseline characteristics between the two groups. On postoperative day 3, no significant difference was observed in the number of radiopaque markers visible in the colon between the groups. All factors associated with bowel recovery, including the time of first flatus, length of hospital stay, amount of food intake, and severity of abdominal discomfort, were similar between the two groups. Mosapride citrate does not benefit the recovery of intestinal motility after minimally invasive gastrectomy in patients with gastric cancer. Therefore, routine postoperative use of mosapride citrate is not recommended in such patients.

Comparing the short-term outcomes of totally intracorporeal gastroduodenostomy with extracorporeal gastroduodenostomy after laparoscopic distal gastrectomy for gastric cancer: a single surgeon's experience and a rapid systematic review with meta-analysis.

BACKGROUND: Since delta-shaped gastroduodenostomy was introduced, many surgeons have utilized laparoscopic distal gastrectomy (LDG) with totally intracorporeal Billroth I (ICBI) for gastric cancer, because it is expected to have several advantages over laparoscopic-assisted distal gastrectomy with extracorporeal Billroth I (ECBI). In this study, we compared these two reconstruction options to evaluate their outcomes. METHODS: The data of 166 gastric cancer patients who underwent LDG performed by a single surgeon between April 2009 and February 2012 were analyzed retrospectively. The subjects were divided into ECBI (n = 106) and ICBI (n = 60) groups, and then the clinical characteristics, surgical outcomes, symptoms, and change in BMI at 3 months after surgery were compared. Furthermore, a rapid systematic review and meta-analysis were conducted. RESULTS: The operative time was significantly shorter in the ICBI group (197.4 ± 45.5 vs. 157.1 ± 43.9 min), but blood loss was similar between the groups. Regarding surgical outcomes, there were no significant differences in the length of hospital stay, soft diet initiation, visual analogue scale, frequency of analgesics injection, and postoperative white blood cell counts and C-reactive protein levels between the groups. The surgical complication rates were 5.7 and 13.3% in the ECBI and ICBI groups, respectively, and one case of anastomosis leakage was observed in each group. At 3 months after surgery, reflux symptoms were more frequent in the ICBI group, but other gastrointestinal symptoms and the change of BMI were similar between the groups. The meta-analysis revealed no significant differences in the operative time, time to first flatus, length of hospital stay, frequency of analgesic usages, and rates of anastomosis complications between the groups. CONCLUSIONS: We could not demonstrate the clinical superiority of ICBI over ECBI based on our data and a rapid systematic review and meta-analysis. The anastomosis method may be selected according to patient conditions and the surgeon's preference.

SFRP4 and CDX1 Are Predictive Genes for Extragastric Recurrence of Early Gastric Cancer after Curative Resection.

Extragastric recurrence of early gastric cancer (EGC) after curative resection is rare, but prognosis has been poor in previous reports. Recently, single patient classifier (SPC) genes, such as secreted frizzled-related protein 4 (SFRP4) and caudal-type homeobox 1 (CDX1), were associated with prognosis and chemotherapy response in stage II-III gastric cancer. The aim of our study is, therefore, to elucidate predictive factors for extragastric recurrence of EGC after curative resection, including with the expression of SPC genes. We retrospectively reviewed electronic medical records of 1974 patients who underwent endoscopic or surgical curative resection for EGC. We analyzed clinicopathological characteristics to determine predictive factors for extragastric recurrence. Total RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue and amplified by real-time reverse transcription polymerase chain reaction to evaluate expression of SPC genes. Overall incidences of extragastric recurrence were 0.9%. In multivariate analysis, submucosal invasion (odds ratio [OR] = 6.351, p = 0.032) and N3 staging (OR = 171.512, p = 0.012) were independent predictive factors for extragastric recurrence. Mean expression of SFRP4 in extragastric recurrence (-2.8 ± 1.3) was significantly higher than in the control group (-4.3 ± 1.6) (p = 0.047). Moreover, mean expression of CDX1 in extragastric recurrence (-4.6 ± 2.0) was significantly lower than in the control group (-2.4 ± 1.8) (p = 0.025). Submucosal invasion and metastasis of more than seven lymph nodes were independent predictive factors for extragastric recurrence. In addition, SFRP4 and CDX1 may be novel predictive markers for extragastric recurrence of EGC after curative resection.

Adverse Prognostic Impact of Postoperative Complications After Gastrectomy for Patients With Stage II/III Gastric Cancer: Analysis of Prospectively Collected Real-World Data.

BACKGROUND: The impact of postoperative complications on the prognosis of gastric cancer remains controversial. This study aimed to evaluate the relationship between postoperative complications and long-term survival in patients undergoing gastrectomy for stage II/III gastric cancer. METHODS: Some 939 patients underwent curative gastrectomy for stage II/III gastric cancer were identified from real-world data prospectively collected between 2013 and 2015. We divided patients according to the presence of serious complications, specifically, Clavien-Dindo grade III or higher complications or those causing a hospital stay of 15 days or longer. RESULTS: Serious complications occurred in 125 (13.3%) patients. Patients without serious complications (64.3%) completed adjuvant chemotherapy significantly more than patients with serious complications (37.6%; p<0.001). The 5-year overall survival(OS) rate was 58.1% and recurrence-free survival(RFS) rate was 58.1% in patients with serious complications, which were significantly worse than those of patients without serious complications (73.4% and 74.7%, respectively; p<0.001 for both). In stage II, once patients completed adjuvant chemotherapy adequately, the OS and RFS of patients with serious complications did not differ from those without serious complications. However, in stage III, the patients with serious complications showed a worse OS even after completion of adequate adjuvant chemotherapy. CONCLUSION: Serious complications after gastrectomy had a negative impact on the prognosis of stage II/III gastric cancer patients. Serious complications worsen the survival in association with inadequate adjuvant chemotherapy. Efforts to reduce serious complications, as well as support adequate chemotherapy through proper management of serious complications, would improve the prognosis of stage II/III gastric cancer patients.

Altered systematic glucose utilization after gastrectomy: correlation with weight loss.

BACKGROUND: Although gastrectomy induces weight loss and improves glucose homeostasis, the mechanism is not clearly elucidated. OBJECTIVE: Weight loss after gastrectomy for gastric cancer may be the result from not only altered nutrition absorption but also systematic endocrinologic changes after bariatric-like surgery. No clinical studies have evaluated the altered glucose metabolism associated with postoperative weight loss in gastric cancer patients. SETTING: A retrospective analysis of a tertiary medical center. METHODS: We evaluated changes in 18 F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography and weight change in patients who underwent gastrectomy. Participants comprised initially overweight (body mass index ≥23 kg/m2), who underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomography at 6 to 12 months after gastrectomy for early gastric cancer (n = 149). Small bowel, subcutaneous white adipose tissue (WAT), and skeletal muscle glycolysis were semiquantified using positron emission tomography/computed tomography. Measures were bifurcated or combined into values that correlated with ≥5% weight loss. RESULTS: Weight (median decrement, -3.3 kg), cholesterol level (-15 mg/dL), and body fat (-26.1%) significantly decreased after surgery. Substantial weight loss was significantly correlated with increased small bowel uptake of 18 F-fluorodeoxyglucose (≥5% weight loss versus <5% weight loss: 1.91 versus 1.69). Patients with an increased bowel uptake showed an increase in WAT uptake (P = .01). Patients with both increased small bowel and WAT uptakes were significantly correlated with weight loss (odds ratio: 9.67, 95% confidence interval 2.65-35.22). CONCLUSIONS: Patients with increased small bowel glycolysis and increased WAT uptake after gastrectomy are likely to lose weight. Altered glucose distribution contributes to improvement of the metabolic parameter after gastrectomy. We have shown evidence of bariatric surgery-like endocrinologic changes in gastric cancer patients who underwent gastrectomy.

Prognostic significance of body mass index and prognostic nutritional index in stage II/III gastric cancer.

INTRODUCTION: Preoperative body weight and nutritional status are related to prognosis in patients with gastric cancer; however, the prognostic impact of postoperative in these variables is unclear. We aimed to investigate the association of preoperative/postoperative body mass index (BMI) and prognostic nutritional index (PNI) with prognosis in patients with gastric cancer. MATERIALS AND METHODS: We retrospectively 1868 patients with stage II/III gastric cancer treated with gastrectomy between January 2006 and December 2010. We divided the populations into 3 groups according to BMI; underweight, normal, and overweight. Patients were divided into 3 groups according to BMI (underweight, normal-weight, overweight). PNI was classified into low and high (cutoff value; 49.7). The association of preoperative BMI/PNI and their changes (6 months postoperatively) with clinicopathologic characteristics were evaluated. RESULTS: Preoperative underweight and low PNI were related to poor prognosis (log-rank p < 0.001 for both). There was a positive correlation between preoperative BMI and PNI (mean preoperative PNI: 51.13 [underweight], 53.37 [normal-weight], and 55.16 [overweight]; p < 0.001). Preoperative BMI and PNI were independent prognostic factors for disease-free survival along with age and TNM stage (p < 0.001 for both). BMI changes from normal-weight to underweight and from overweight to normal/underweight were related to poor prognosis (log-rank p = 0.021 and p = 0.013, respectively). PNI changes were related to prognosis in both the preoperative low and high PNI groups (p < 0.001 and p = 0.019, respectively). CONCLUSION: Preoperative BMI and PNI and their postoperative changes are related to prognosis in patients with stage II/III gastric cancer. Careful nutritional intervention after gastrectomy can improve prognosis.