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Epithelial-mesenchymal transition (EMT) is a crucial mechanism that facilitates cancer cell metastasis. Despite its importance, the clinical significance of EMT in gastric cancer (GC) patients has yet to be clearly demonstrated. For gauging the extent of EMT in GC, we employed gene set variation analysis to score 807 patient samples from two large cohorts: TCGA and GSE84437. In both cohorts, EMT high GC showed a significant association with worse overall survival (hazard ratio (HR) = 1.74, p = 0.011 and HR = 2.01, p < 0.001, respectively). This association was stronger when considering the EMT signature score compared to the individual expressions of EMT-related genes (CDH1, CDH2, VIM, and FN1). While the EMT signature level did not differ among various cancers, high EMT signature specifically correlated with survival in GC alone. Mucinous and diffuse histological types exhibited higher EMT levels compared to others (p < 0.001), and the EMT signature level was correlated with tumor depth and AJCC stage (all p < 0.001). Interestingly, the EMT score was an independent factor for overall and disease-specific survival (multivariate; p = 0.006 and 0.032, respectively). EMT high GC displayed a lower fraction of Th1 cells and a higher fraction of dendritic cells, M1 macrophages and several stromal cells. EMT high GC exhibited an inverse correlation with cell proliferation-related gene sets. While they significantly enriched multiple pro-cancerous gene sets, such as TGF-β signaling, hypoxia, and angiogenesis. The presence of EMT signature in a bulk tumor was linked to TGF-β signaling, hypoxia, and angiogenesis, and was also associated with poorer survival outcomes in GC patients., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background/aim: Ramucirumab plus paclitaxel has been widely used as a second-line chemotherapy for treating advanced gastric cancer. However, the real-world data of this regimen for older patients with gastric cancer (GC) remains unrevealed. The aim of this study was to clarify the feasibility and efficacy of this regimen for older patients with GC in a single-arm, phase II study., Patients and Methods: Patients aged ≥70 years having unresectable or recurrent GC who met the eligible criteria were enrolled. Paclitaxel was administered at a dose of 80 mg/m 2 on days 1, 8, and 15, and ramucirumab was administered at a dose of 8 mg/kg on day 1 and day 15 of a 4-week cycle. Primary endpoint was the incidence of adverse events and secondary endpoints were response rate, progression-free survival, and overall survival. A total of 25 patients were enrolled in the full-set analysis., Results: Grade 3 or more adverse events were observed in 21 patients (84.0%). Neutropenia was most frequently observed (68.0%), followed by peripheral sensory neuropathy (12.0%), and febrile neutropenia (12.0%). Median progression-free survival and overall survival were 6.9 months and 13.4 months, respectively. Disease control rate was 88.0%, and response rate of patients with measurable lesions was 52.9%. Notably, no treatment-related deaths occurred., Conclusion: Ramucirumab plus paclitaxel as a second-line chemotherapy demonstrated acceptable oncological outcomes, despite the occurrence of frequent adverse events. It is necessary to carefully select patients and adjust treatment regimens in older patients with GC to safely administer chemotherapy and subsequently achieve satisfactory long-term outcomes., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In the previous phase I/II study, we established neoadjuvant chemotherapy (NAC) using bi-weekly docetaxel, cisplatin, and S-1 (DCS) for clinical stage III gastric cancer. This study aimed to clarify long-term outcomes of this treatment., Patients and Methods: Relapse-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method and prognostic factors for RFS and OS were identified by univariate analysis., Results: A total of 47 patients with clinical stage III gastric cancer were enrolled in this study. The 5-year RFS and OS rates were 69.8% and 74.3%, respectively, in all registered patients. Moreover, the 5-year OS and RFS rates in patients receiving R0 gastrectomy were 68.0% and 79.4%, respectively. Neutrophil-lymphocyte ratio (NLR) before NAC ≥2.41, prognostic nutritional index (PNI) before NAC ≤50.4, Glasgow prognostic score before NAC classification 2, NLR after NAC ≥1.43, PNI after NAC <48.0, and Grade 1a/1b pathological response significantly worsened RFS. NLR after NAC ≥1.43, PNI before NAC ≤50.4, NLR after NAC ≥1.43, and body weight loss >5 kg after NAC significantly worsened OS., Conclusion: Although bi-weekly DCS therapy as neoadjuvant setting showed acceptable long-term outcomes, poor immune-nutritional status before and after NAC caused worse long-term survival in stage III gastric cancer patients. It is warranted to conduct a well-designed prospective randomized control study to compare long-term outcomes using the bi-weekly DCS regimen between patients with and without immune-nutritional support during peri-NAC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Prophylactic splenectomy for hilar lymph node (#10) dissection has shown no survival benefit for patients with proximal advanced gastric cancer that does not invade the greater curvature. However, the survival benefit of prophylactic splenectomy for proximal advanced gastric cancer invading the greater curvature side, particularly for clinically negative #10 lymph node metastasis (#10[-]) cases remains controversial., Methods: This multi-institutional retrospective study enrolled 146 consecutive patients with proximal advanced gastric cancers invading the greater curvature side with clinical #10(-) who underwent R0 total gastrectomy. For 33 of these patients, splenectomy was performed, and the remaining 113 underwent spleen-preservation gastrectomy. Short- and long-term results were compared between the splenectomy and spleen-preservation groups, with the incidence of #10 metastasis in the splenectomy group and recurrence in the spleen-preservation group compared., Results: In the splenectomy group, longer operative time, greater blood loss, more frequent postoperative abdominal infection, and longer hospital stay were observed than in the spleen-preservation group. The two groups exhibited no differences in median relapse-free survival time (31.1 vs 59.8 months; P = 0.684) or median overall survival time (64.9 vs 65.1 months; P = 0.765). The pathologic #10 lymph node metastasis rate was 3% in the splenectomy group, and the #10 lymph node recurrence rate was 2.7% in the spleen-preservation group., Conclusions: Prophylactic splenectomy showed more frequent postoperative morbidities and a longer hospital stay than spleen preservation, without any long-term survival benefits., (© 2022. Society of Surgical Oncology.)

Aim: The significance of sarcopenia in cancers has been widely recognized. However, few studies have focused on chronological changes in sarcopenia in cancer patients. This study aimed to clarify the clinical significance of changes in the psoas muscle area before and after preoperative chemotherapy., Methods: This study included 39 patients who underwent gastrectomy followed by preoperative chemotherapy for advanced gastric cancer between January 2010 and December 2016 in our hospital. The psoas muscle area was measured at the umbilical level before and after chemotherapy, and the relationship between its chronological changes and the long-term prognosis was examined., Results: Patients were classified into two groups according to changes in the psoas muscle area before and after preoperative chemotherapy: remarkable muscle depletion and normal groups. No significant differences were observed in clinicopathological factors. Notably, the remarkable muscle depletion group included significantly more male patients (P = .018) and showed a high weight loss rate (P < .001). Although no significant difference was observed in the recurrence-free survival between the two groups (P = .484), overall survival was significantly worse in the remarkable muscle depletion group (P < .001). Multivariate analysis for prognosis revealed that pathological stage III or higher (P = .022) and decreased psoas muscle area (P = .038) were independent prognostic factors., Conclusions: The present findings suggest that psoas muscle depletion during preoperative chemotherapy is a prognostic factor for poor long-term outcomes in patients who underwent gastrectomy followed by preoperative chemotherapy for advanced gastric cancer., (© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Introduction: The benefits of surgery in older patients with gastric cancer are controversial. This single-institution retrospective study in Japan aimed to evaluate the impact of gastrectomy in older patients with gastric cancer., Methods: A series of 234 patients aged ≥80 years with histologically confirmed gastric cancer had indications for surgical treatment at the Gastroenterological Center, Yokohama City University Medical Center, between April 2002 and December 2018. Patients who were lost to follow-up (n = 27), had tumors not eligible for surgery (n = 14), and could not achieve R0 resection (n = 7) were excluded from this retrospective study. The remaining 186 patients were included. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were evaluated., Results: The incidence of postoperative complications with Clavien-Dindo grade ≥ II was observed in 61 patients (32.8%). The 5-year relapse-free survival and overall survival (OS) rates were 84.2% and 63.4%, respectively. Multivariate analysis showed that geriatric nutritional risk index (<98) (odds ratio, 1.97; p = 0.047), neutrophil/lymphocyte ratio (>2.36) (odds ratio, 1.94; 95% confidence interval, 1.02-3.67; p = 0.043), and total gastrectomy (TG) (odds ratio, 1.97; p = 0.042) significantly predicted postoperative complications. Moreover, TG (hazard ratio, 1.91; p = 0.036) was an independent prognostic factor of OS., Conclusions: Poor immunonutritional status and TG led to worse short-term outcomes. Moreover, TG was an independent prognostic factor of OS in older patients with gastric cancer. It is necessary to provide effective perioperative care, including nutritional support, to clarify whether short-term outcomes would be improved., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Patients and Methods: Patients with gastric cancer who underwent laparoscopic-assisted pylorus-preserving gastrectomy (LAPPG group)or laparoscopic-assisted distal gastrectomy(LADG group)between January 2010 and December 2019 were reviewed and their postoperative nutritional status and long-term outcomes retrospectively evaluated., Results: In total, 83 patients(LAPPG group, n=23; LADG group, n=60)were included. Weight loss rates 1, 6, 12, and 24 months postoperatively in the LAPPG and LADG groups were 5.7% and 7.1%, 6.6% and 9.6%, 5.8% and 10.1%, and 5.2% and 8.7%, respectively. The LADG group exhibited a significantly higher weight loss than the LAPPG group at 6, 12, and 24 months (p=0.007, 0.002, and 0.022, respectively). No recurrence was observed in either group within 5 years of surgery. The 5- year overall survival rate of patients with pathological Stage Ⅰ cancer( LAPPG group, n=23, LADG group, n=51) was higher in the LAPPG group than in the LADG group(100% vs 82.9%, p=0.027). There were 6 cases of death from other diseases in the LADG group(pneumonia, n=2, other cancer, n=2, postoperative bleeding, n=1, and heart failure, n=1)but none in the LAPPG group., Conclusion: The weight loss after LAPPG was significantly lower than that after LADG. Furthermore, the former showed a good prognosis without death from other diseases, such as pneumonia.

Background: Long-term outcomes in gastric cancer patients with positive lavage cytology (CY1) are generally poor. This multi-institutional retrospective cohort study aims to evaluate the clinical significance of the neutrophil-lymphocyte ratio (NLR) and the lymphocyte-monocyte ratio (LMR) in CY1 gastric cancer patients., Methods: A total of 121 CY1 gastric cancer patients without other non-curative factors, who underwent macroscopically curative resection, were enrolled in this study. The cutoff values of preoperative NLR (pre-NLR), postoperative NLR (post-NLR), preoperative LMR (pre-LMR), and postoperative LMR (post-LMR) were defined by the Contal and O'Quigley method as 2.3, 3.0, 2.5, and 3.2, respectively. A Cox proportional hazard model was used to identify the independent prognostic factors among NLR, LMR, and other clinicopathological factors., Results: There were significant differences in the overall survival (OS) between the two groups: high post-NLR groups vs. low post-NLR group (median survival time, months) (10.9 vs. 22.8, P = 0.006) and high pre-LMR group vs. low pre-LMR group (21.3 vs. 11.0, P = 0.001). The LMR value elevated significantly after gastrectomy (P = 0.020), although not in the NLR value (P = 0.733). On multivariate analysis, high post-NLR (hazard ratio = 1.506; 95% confidence interval = 1.047-2.167; P = 0.027), low pre-LMR (1.773; 1.135-2.769, 0.012), and no postoperative chemotherapy (1.558; 1.053-2.305, 0.027) were found to be independent prognostic factors for adverse OS., Conclusions: Because a combination of high post-NLR and low pre-LMR may be an adverse prognostic marker in resectable CY1 gastric cancer patients, it is necessary to conduct a prospective trial to confirm a useful perioperative chemotherapeutic regimen for these patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer., Objectives: This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer., Methods: We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve., Results: Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival., Conclusions: The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Converse Ω anastomosis is a recently developed technique of delta-shaped anastomosis for intracorporeal gastroduodenostomy to simplify the anastomotic procedures and reduce their potential risks. This study aimed to evaluate the safety and effectiveness of converse Ω anastomosis, comparing it with conventional extracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer., Patients and Methods: Among 169 gastric cancer patients who underwent LDG with Billroth-I anastomosis anastomosis between April 2013 and March 2018, we selected 100 patients by propensity score matching (50 in the converse Ω anastomosis group and 50 in the extracorporeal anastomosis group). Patients' characteristics, intraoperative outcomes, postoperative complications, and survival time were compared between the 2 groups., Results: Median anastomosis time was significantly longer in the converse Ω group than in the extracorporeal group (40.0 vs. 30.5 min, P=0.005). However, the total procedure time did not differ significantly between the groups. Intraoperative blood loss volume was significantly lower in the converse Ω group than in the extracorporeal anastomosis group (40 vs. 120 mL, P<0.001). There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, or length of hospital stay. The postoperative body mass index and the prognostic nutritional index did not differ between the groups 1 year after surgery. There were no significant differences in overall survival and relapse-free survival between the 2 groups., Conclusions: Converse Ω anastomosis is feasible and safe. This novel technique can be adopted as a treatment option for reconstruction after LDG in patients with early-stage gastric cancer. Therefore, the risks and benefits of converse Ω anastomosis after LDG should be confirmed in larger cohorts., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear., Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated., Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1-100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141-0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS., Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background/aim: Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach., Materials and Methods: A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen., Results: Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The purpose of this study was to evaluate the safety and efficacy of laparoscopic total gastrectomy (LTG) for elderly patients., Patients and Methods: We retrospectively analyzed 136 patients who underwent LTG. We divided the patients into elderly patients (>75 years of age) and non-elderly patients (≤75 years of age)., Results: The American Society of Anesthesiologists score, Charlson comorbidity index, Glasgow Prognostic Score and rate of comorbidities were higher in the elderly group; the rates of other clinicopathological characteristics did not differ between the two groups. Regarding the nutritional status, the body weight loss rate in the elderly group was higher in comparison to the non-elderly group (81% vs. 84%, p=0.004). The disease-specific survival (DSS) did not differ between two groups to a statistically significant extent (3-year DSS rates: 83.7 vs. 94.5%; p=0.152)., Conclusions: LTG was acceptable for elderly patients as the elderly and non-elderly groups showed comparable short-term and long-term outcomes., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Low serum carnitine levels have been reported in patients with cancer receiving chemotherapy and are considered one of the factors causing fatigue associated with chemotherapy. We evaluated the effectiveness of L-carnitine in the treatment of fatigue associated with chemotherapy in patients with gastric cancer(GC)., Materials and Methods: We performed a randomized controlled trial between December 2013 and December 2018. Untreated patients with advanced GC were included in the study; 1 patient developed an allergy after receiving the first chemotherapy and was excluded from the study. The primary endpoint was brief fatigue inventory(BFI). Patients were categorized into 2 groups: those who received L-carnitine oral supplements(group C)and those who did not receive L-carnitine oral supplements(group N)., Results: The serum carnitine levels were improved significantly in group C compared with group N. BFIwas more aggravated in group N than group C; however, the difference was not significant., Conclusion: We could not demonstrate the effectiveness of L-carnitine in the treatment of fatigue associated with chemotherapy in patients with GC.

Background: A retrospective study was performed to evaluate the predictive factors for performing curative-intent surgery and prognostic factors for long-term survival of patients undergoing surgery for stage IV gastric cancer., Patients and Methods: Between 2001 and 2017, 271 patients with stage IV gastric cancer with distant metastasis who underwent systemic chemotherapy were enrolled. Logistic regression analysis was performed to evaluate predictive factors for curative-intent surgery. Cox proportional hazards regression model was applied for patients who were subsequently treated with curative-intent surgery to identify prognostic factors for long-term survival., Results: Curative-intent surgery was performed in 48 patients (17.7%). Median survival time was significantly longer in the surgery group than in the nonsurgery group (53 vs. 11 months, p < 0.0001). R0 resection was performed in 35 patients (72.9%). The three-year overall survival (OS) rates of the R0, R1, and R2 surgery groups were 75.4%, 33.3%, and 25.0%, respectively (p = 0.0002). Logistic regression analysis revealed that lymphogenous distant metastasis alone (odds ratio = 3.276, p = 0.004), positive lavage cytology alone (6.394, 0.014), doublet or triplet chemotherapy (4.064, 0.034), and high Glasgow prognostic score (0.276, 0.001) were independent predictive factors for performing curative-intent surgery. Among patients undergoing surgery, the Cox proportional hazards regression model for OS showed that R0 surgery was an independent prognostic factor for favorable OS (hazard ratio 0.188, p = 0.022)., Conclusions: Patients with lymphogenous distant metastasis alone, P0CY1 alone, good immunonutritional status, and doublet/triplet chemotherapy are candidates for performing effective curative-intent surgery. R0 surgery is crucial for improving long-term survival after surgery.

Purpose: The therapeutic outcomes of stage III gastric cancer patient receiving D2 gastrectomy and adjuvant chemotherapy remain unsatisfactory. To improve the long-term outcomes in this population, the combination of docetaxel and S-1 (DS) therapy can be expected to be a useful regimen as neoadjuvant chemotherapy (NAC). This study aimed to prospectively evaluate the efficacy of NAC-DS for clinical stage III gastric cancer., Methods: Between January 2010 and December 2013, 26 patients were enrolled. Patients with clinical stage III gastric cancer received two courses of docetaxel 40 mg/m 2 on day 1, 15 and S-1 40 mg/m 2 bid orally on day 1-7, 15-21 every 4 weeks, followed by radical D2 gastrectomy. Short- and long-term outcomes were evaluated. This study was approved by the ethics committee of Yokohama City University, and was registered in the University Hospital Medical Information Network (UMIN) database (ID: 000011521)., Results: Of 26 patients, 24 (92.3%) patients completed two courses of NAC. After NAC-DS, Grade 3 neutropenia was observed in 5 (19.2%) patients including one patient with febrile neutropenia, anemia in 1 (3.8%) patient and diarrhea in 1 (3.8%) patient. All patients underwent R0 gastrectomy and pathological response was found in 15 (57.6%) patients. Postoperatively, Clavien-Dindo grade II complication occurred in 8 (30.7%) patients and no mortality was observed. The 5-year overall survival (OS) was 57.7%, median OS was 78.7 months and recurrence free survival (RFS) was 49.0%, median RFS was 45.4 months with 66.5 months median follow-up. Pathological response (HR = 0.091, 95% CI 0.011-0.730, p = 0.016) and > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for recurrence, > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for overall survival by multivariate analysis., Conclusions: NAC-DS demonstrated acceptable toxicity with a high R0 resection rate in clinical stage III gastric cancer patients, especially in patients with good nutritional status. Further prospective study is warranted to compare the long-term outcomes between with and without NAC-DS.

Background/aim: Nanoparticle albumin-bound (nab)-paclitaxel has demonstrated antitumor activity against advanced gastric cancer. However, gastric cancer patients can be difficult to treat with the recommended dose because of the high incidence of adverse toxicities. The aim of this study was to evaluate the safety and effectiveness of low-dose nab-paclitaxel in a multicenter, single-arm, phase II study., Patients and Methods: Treatment included low doses of 180 mg/m 2 nab-paclitaxel administered on day 1 of each 21-day cycle. The primary endpoint was defined as the overall response rate (ORR). The secondary endpoints included progression-free survival (PFS), safety, and overall survival (OS). A total of 34 patients were enrolled in the full-analysis set., Results: The ORR was 5.9%. The median PFS and OS were 2.4 months and 9.2 months, respectively. The most common grade 3/4 toxicities were anemia (8.8%), neutropenia (5.9%), appetite loss (5.9%) and peripheral sensory neuropathy (5.9%). No treatment-related deaths occurred., Conclusion: The tri-weekly low dose of nab-paclitaxel therapy is effective towards advanced gastric cancer patients with good tolerability and an acceptable margin of safety., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The technical feasibility and oncologic efficacy of reduced-port laparoscopic gastrectomy (RPG) for gastric cancer remain unclear., Methods: A series of 767 patients with gastric cancer who underwent R0 laparoscopic gastrectomy were retrospectively matched for age, gender, American Society of Anesthesiology score, body mass index, surgeon, lymph node dissection, and pathologic stages by propensity scoring. Finally, data from 274 patients (74 conventional laparoscopic distal gastrectomy [CLDG] cases, 74 reduced-port distal gastrectomy [RPDG] cases, 63 conventional laparoscopic total gastrectomy [CLTG] cases, and 63, reduced-port total gastrectomy [RPTG] cases) were selected for analysis., Results: Compared with the conventional group, the reduced-port group had significantly longer operation times (RPDG 265 min vs CLDG 239 min; p = 0.001 and RPTG 305 min vs CLTG 285 min; p = 0.012) and reduced blood loss (RPDG 48 ml vs CLDG 68 ml; p = 0.001 and RPTG 75 ml vs CLTG 110 ml; p = 0.026). The number of dissected lymph nodes was significantly higher in the CLDG group than in the RPDG group (38 vs 31; p = 0.002). Cosmetic satisfaction showed significant superiority in the reduced-port group compared with the conventional group. No significant difference was observed in overall survival (OS) (5-year OS: RPDG 100% vs CLDG 96.7%; p = 0.207 and RPTG 91.6% vs CLTG 91.8%; p = 0.615) or relapse-free survival (RFS) (5-year RFS: RPTG 92.3% vs CLTG 92.1%; p = 0.587)., Conclusions: The study results suggest that RPG for gastric cancer by an experienced surgeon is a feasible and safe technique. The RPG procedure can be presented to patients as one of the effective treatment options.

Background/aim: The aim of this phase I/II study was to determine the safety, and efficacy of combination of neoadjuvant chemotherapy (NAC) with biweekly docetaxel, cisplatin, and S-1 (DCS) in stage III gastric cancer patients., Patients and Methods: In the phase I study, S1 was administered at doses of 80 mg/day to 120 mg/day depending on the body surface area and docetaxel was administered at 20 mg/m 2 , whereas cisplatin was initially administered at 25 mg/m 2 and was escalated by 5 mg/m 2 up to 50 mg/m 2 In the phase II study, safety and therapeutic efficacy of DCS were evaluated using the recommended dose of cisplatin., Results: In phase I, 21 patients were enrolled. In level II, perforation of gastric cancer occurred in one case although no dose limiting toxicities (DLTs) were noted in level III-VI. Recommended dose for cisplatin was 50 mg/m 2 /day. In phase II, among 47 patients, 14 experienced grade 3/4 adverse events. Clinically, response rate was 66.7% and disease control rate was 97.9%. The curative (R0) resection rate was 95.7%. Pathological response rate was 53.3%. Three-year overall survival and relapse-free survival rates were 78.5% and 65.3%, respectively., Conclusion: Biweekly DCS as NAC was efficient, safe, and acceptable; however, long-term survival should be evaluated to confirm the efficacy of biweekly DCS for stage III gastric cancer patients., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The present study evaluated the safety and effectiveness of laparoscopic gastrectomy (LG) in elderly gastric cancer patients., Patients and Methods: This study included 78 gastric cancer patients aged 80 years or above [39 in the LG group and 39 in the open gastrectomy group (matched)]. Patient characteristics, surgical outcomes, survival time, and immunonutritional status were compared., Results: Mean blood loss was significantly lower in the LG group, although the operation time did not differ. There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, total hospital stay, and the causes of death. The prognostic nutritional index and skeletal muscle index at 1 year were better maintained in the LG group than in the open gastrectomy group. The overall and relapse-free survivals did not differ., Conclusions: LG may be feasible in elderly patients with gastric cancer. A prospective randomized controlled trial should be conducted to confirm its efficacy.

Background/aim: The purpose of this study was to reveal the optimal lymph node (LN) dissection in remnant gastric cancer (RGC) patients., Patients and Methods: We retrospectively analyzed 46 RGC patients divided into two groups: patients who underwent initial gastrectomy for benign (group B) and malignant (group M) diseases., Results: Metastasis was more frequently observed at the left (nos. 2, 4sa, 4sb, 10, and 11p/d) and right (nos. 1, 3, 4d, 7, 8a, and 12a) side LNs of RGC in groups M and B. Modified IEBLD scores (frequency of LN metastasis by median survival time of patients with metastatic LNs) were high at station nos. 10 (4.7), 11p/d (4.3/9.9), and 16 (4.3) in group M and nos. 1 (2.1), 7 (1.9) and mesojejunal (3.0) in group B., Conclusion: After lymphadenectomy for initial gastric cancer, lymphatic flow toward the splenic artery was predominant. Therefore, splenectomy with para-aortic LN dissection is an option., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aims: The study aimed to clarify the risk factors for anastomotic leakage after laparoscopy-assisted total gastrectomy (LATG) for gastric cancer., Methods: In this study, we enrolled 131 patients with preoperatively diagnosed early gastric cancer who underwent LATG by a single surgeon between June 2006 and February 2014 at the Department of Surgery, Gastroenterological Center, Yokohama City University. Risk factors for anastomotic leakage (esophagojejunostomy) after LATG were retrospectively evaluated by univariate and multivariate analyses., Results: Anastomotic leakage of the esophagojejunostomy was observed in 13 (9.9%) of 131 patients. Univariate analysis of risk factors for anastomotic leakage revealed that the prognostic nutritional index (PNI) is a risk factor for anastomotic leakage (<55, 11 of 63 vs. ≥55, 2 of 55; p = 0.039). Multivariate analysis revealed that PNI is an independent risk factor for anastomotic leakage (OR 0.208; 95% CI 0.044-0.981; p = 0.047)., Conclusion: Gastric cancer patients with a low PNI have a higher risk for anastomotic leakage after LATG. The results of this study must be confirmed by a study with a large cohort of patients receiving LATG reconstructed using the same method by experienced surgeons in multiple institutions., (© 2017 S. Karger AG, Basel.)

We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy for liver metastasis of gastric cancer. A 76- year-old man who had received SOX therapy for metastatic gastric cancer was admitted to our hospital for a chief complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to SOX therapy because of his symptoms and because his laboratory studies showed significant elevation of his serum creatine kinase(CK)level. The symptoms disappeared and the CK level normalized following large-volume transfusions. Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event. This is the first detailed case report of rhabdomyolysis related to SOX therapy.

Background: Performing routine prophylactic cholecystectomy during gastrectomy in gastric cancer patients has been controversial. The frequency of cholelithiasis, cholecystitis, and cholangitis after gastrectomy has not been reported for large patient populations, so we carried out this retrospective study to aid the assessment of the necessity for prophylactic cholecystectomy., Methods: This retrospective study reviewed 969 patients with gastric cancer who underwent distal gastrectomies with Billroth I reconstructions (DG) or total gastrectomies with Roux-en-Y reconstructions (TG), preserving the gallbladder, between January 2000 and May 2012. Risk factors for cholelithiasis, cholecystitis, and cholangitis after gastrectomy were evaluated using logistic regression analysis., Results: The median follow-up period after gastrectomy was 48 months (range 12-159 months). After gastrectomy, cholelithiasis occurred in 6.1% (59/969) patients and cholecystitis and/or cholangitis occurred in 1.2% (12/969) patients. The method used for gastrectomy was an independent risk factor for both cholelithiasis (TG/DG: OR (95%CI): 1.900 (1.114-3.240), p = 0.018) and cholecystitis and/or cholangitis (TG/DG: OR (95%CI): 8.325 (1.814-38.197), p = 0.006). In patients who developed cholelithiasis, the incidence of cholecystitis and/or cholangitis was 31.3% (10/32) after TG, but only 7.4% after DG., Conclusions: Prophylactic cholecystectomy may be unnecessary in distal gastrectomy with Billroth I reconstruction.

Background/aims: Osteoporosis is found to have high prevalence after gastrectomy and therefore, it is important to prevent this condition by means of effective medication, such as alendronate sodium hydrate., Methods: A total number of 48 gastric cancer patients diagnosed with osteoporosis after R0 gastrectomy was registered in this study between December 2013 and August 2014. Twenty-three patients received intravenous (i.v.) alendronate sodium hydrate and 25 patients received the drug in an oral jelly form. Serological and urinary examinations related to bone metabolism and bone mineral density (BMD) were performed periodically and the results obtained from the 2 groups were compared., Results: BMD increased, serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b, and the urine level of urine N-terminal telopeptide decreased with time in both groups. However, the serum Ca level did not change. Two-way analysis of variance revealed no significant differences in these factors between the 2 groups., Conclusion: It is essential to prevent both forms of osteoporosis by using alendronate sodium hydrate after gastrectomy for gastric cancer. A prospective, randomized, controlled trial in many patients following long duration should be conducted to clarify the benefits of i.v. alendronate sodium hydrate., (© 2017 S. Karger AG, Basel.)

Background: Although a few studies have reported the use of reduced-port laparoscopic gastrectomy (RPG) in gastric cancer patients, the feasibility of routinely using this technique remains unclear. It is therefore important to evaluate the surgical advantages of this technique in this patient group., Methods: Between August 2010 and July 2015, 165 patients underwent RPGs at our hospital, performed by a single surgeon. Of these patients, 88 underwent reduced-port laparoscopic distal gastrectomy (RPLDG) and 77 underwent reduced-port laparoscopic total gastrectomy (RPLTG). In addition to short-term surgical outcomes after RPG, survival times and the surgical learning curve were also evaluated., Results: Blood losses during lymph node dissection in the RPLDG and RPLTG groups were not significantly different (p = 0.160). Conversion to open surgery was necessary in only two patients. Postoperative morbidities were observed in 14.8 % of the RPLDG group and 14.3 % of the RPLTG group, but there were no deaths. Most patients expressed high cosmetic satisfaction in both groups. In the RPLDG group, operation time during reconstruction decreased over the first 50 cases and then plateaued, as the surgeon's experience of the technique increased. In contrast, in the RPLTG group, operation times dropped with surgical experience for both lymph node dissection, plateauing after 40 cases, and for reconstruction, plateauing after 30 cases. Only three patients died of gastric cancer in the follow-up period and three patients died of other diseases. Five-year overall survival and 5-year disease-specific survival were 95.6 and 98.0 %, respectively., Conclusions: We have shown that reduced-port gastrectomy (RPG) could be an acceptable and satisfactory procedure for treating gastric cancer for an experienced laparoscopic gastric surgeon who has sufficient previous experience of conventional laparoscopic gastrectomies.

Background: Pulmonary metastasectomy has come to be recognized as an effective treatment for selected patients with some malignancies. On the other hand, the role of pulmonary metastasectomy for gastric cancer is still unknown. Metastasectomy is rarely indicated in cases of pulmonary metastasis from gastric cancer, because in most cases, the metastasis occurs in the form of lymphangitic carcinomatosis and the lesions are numerous. The purpose of this study was to determine the surgical outcomes and prognostic factors for survival after pulmonary metastasectomy., Methods: From 1985 to 2012, 10 patients underwent pulmonary metastasectomy for gastric cancer at Saitama Cancer Center, Japan. The overall survival rate was examined by the Kaplan-Meier method and univariate analysis was carried out to identify prognostic factors., Results: The overall 3-year survival rate was 30.0 %. The median follow-up period was 26.8 months (range, 6.5-96.6) after the pulmonary metastasectomy. Univariate analysis revealed an advanced pathological stage of the gastric cancer and occurrence of extrapulmonary metastasis before the pulmonary metastasectomy as unfavorable prognostic factors., Conclusion: Pulmonary metastasectomy should be considered in selected patients with lung metastasis from gastric cancer. An advanced pathological stage of gastric cancer and occurrence of extrapulmonary metastasis before the pulmonary metastasectomy are unfavorable prognostic factors.

A 70-year-old man with left abdominal pain was referred to our hospital, and was diagnosed with type 1 advanced gastric cancer with lymph node metastasis. Neoadjuvant chemotherapy(NAC)with docetaxel and S-1 combination was administered. After 2 courses of chemotherapy, total gastrectomy with D2 lymph node dissection, splenectomy, and cholecystectomy were performed. Pathologically, viable cancer cells were not evident in the primary lesion and lymph nodes. The pathological response of NAC was judged to be Grade 3. On immunohistochemical analysis of the biopsy specimens obtained before treatment, the cancer cells were positive for class III b-tubulin and negative for TS, DPD, and ERCC1. The anti-tumor effect of S-1 may have led to the pCR.

Background: Neoadjuvant chemotherapy (NAC) has been widely adopted for patients with advanced gastric cancer; however, the safety of gastrectomy with D2 lymphadenectomy followed by NAC has not yet been evaluated. We retrospectively analyzed the influence of NAC on morbidity and mortality after gastrectomy in patients with advanced gastric cancer., Patients and Methods: A series of 364 patients with advanced gastric cancer who underwent gastrectomy without pancreatectomy between January 2008 and December 2010 at eight hospitals registered to the Yokohama Clinical Oncology Group were studied retrospectively. There were 330 patients who underwent surgical treatment immediately after diagnosis (surgery alone group) and 34 patients (NAC group) who first received NAC and then underwent surgical resection., Results: Although there were no significant differences in the morbidity rate between the two groups, postoperative pancreatic fistula was more often observed in NAC patients than in patients of the group treated with surgery alone [5 cases (14.7%) vs. 11 cases (3.3%); p=0.011]. In the univariate analysis, NAC (p=0.029), bursectomy (p<0.001) and operative bleeding (≥300 ml, p=0.002), were significantly correlated with postoperative pancreatic fistula, and NAC [odds ratio (OR)=4.901, 95% confidence interval (CI)=1.455-16.67; p=0.010] and bursectomy (OR=11.2, 95% CI=3.460-37.04; p<0.001) were independent risk factors for postoperative pancreatic fistula by multivariate analysis. The incidence of postoperative pancreatic fistula was 40.0% among patients who underwent gastrectomy with bursectomy followed by NAC., Conclusion: The incidence of pancreatic fistula in patients treated with NAC and bursectomy was significantly higher than that in other patients. Bursectomy may be discouraged for the prevention of pancreatic fistula from gastrectomy following NAC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A 59-year-old man presented with epigastralgia. A diagnosis of advanced gastric cancer MLU, Circ, Type 3, 160 mm, tub2, cT4b (SI: panc), cN1, cM0, cH0, cP0, cCY0, cStage ⅢB was made. Because of difficulty with oral intake due to malignant outlet obstruction and tumor bleeding, endoscopic self-expanding metallic stent placement was performed. We administered chemotherapy involving docetaxel, cisplatin, and S-1(DCS). After 2 courses of chemotherapy, the primary lesion and regional lymph nodes had reduced in size. His response was judged as SD according to the RECIST criteria. The patient elected to undergo explorative laparotomy for assessment of the gastric cancer. The intraoperative findings showed that there was no pancreatic invasion, peritoneal dissemination, or distal metastasis, so a total gastrectomy and D2 lymph node dissection was performed. The pathological findings showed that there were very few cancer cells in the primary lesion, and a lymph node metastasis was found. The final stage was gastric cancer MLU, Circ, Type 3, 100 mm, muc, ypT4a(SE), ypN3a (13/51), ypM0, ypH0, ypP0, ypCY0, ypStage ⅢC. The therapy evaluation was Grade 1b. In summary, we encountered a patient with gastric cancer in whom curative surgery was made possible by undergoing chemotherapy and metallic stent placement.

Background: The feasibility of using reduced-port laparoscopic total gastrectomy (RPLTG) for the treatment of gastric cancer remains unclear. This study aimed to address the potentially important advantages of this surgical technique., Methods: Between April 2002 and February 2014, 90 patients underwent laparoscopy-assisted total gastrectomies, performed by a single surgeon. Of these, 45 patients underwent RPLTG and 45 patients underwent conventional laparoscopy-assisted total gastrectomy (CLATG). Short-term outcomes were compared to evaluate the feasibility of RPLTG for gastric cancer., Results: There were several significant differences between the RPLTG and CLATG groups in short-term outcomes: the mean total operation durations were significantly longer in the RPLTG group (319.0 min) than in the CLATG group (259.0 min). However, the mean volume of blood loss, the degree of lymph node dissection, and the number of dissected lymph nodes did not differ between the two groups., Conclusions: We have shown that RPLTG could be an acceptable and satisfactory procedure for the treatment of gastric cancer requiring total gastrectomy for surgeons sufficiently experienced in CLATG.

Background: Long-term outcomes of patients with peritoneal dissemination of gastric cancer remain unsatisfactory despite advances in treatment modalities. Internal luminescence conditionally replicative adenovirus (CRAd) presents a novel approach for cancer treatment and imaging., Materials and Methods: 3CL is a modified cyclooxygenase-2 (COX2) promoter-driven CRAd which contains the luciferase expression gene for bioluminescence imaging. The visualizing and therapeutic effect of 3CL was evaluated in a mouse model of peritoneal dissemination., Results: Intraperitoneal injection of 3CL achieved the shrinkage and reduction of lesions of peritoneal dissemination. Six model mice treated with 3CL had a significantly longer mean survival time than 6 mock-treated mice (85.7 versus 34.3 days, p=0.0005). By whole-body bioluminescent imaging, the sensitivity and specificity of peritoneal dissemination detection through macroscopic inspection were 58.1% and 83.2%, respectively, whereas 3CL viral imaging modality yielded corresponding values of 78.8% and 99.3%. Peritoneal lesions detected by imaging histologically contained cancer cells and necrotic tissue, which originated from viral oncolytic effects., Conclusion: Cox2 CRAds with 5/3 chimeric-fiber modification, therefore, appear to be a promising imaging and therapeutic tools for peritoneal dissemination of gastric cancer., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC.

Background: Laparoscopic total gastrectomy (LTG) has been performed since 1999. Although surgical outcomes have been reported from Japan, Korea, China, and many Western countries, the effectiveness of this technique has not been conclusively established. This study therefore aimed to review the literature systematically., Methods: Our search of the research literature identified 150 studies, which were mostly retrospective and from single institutions., Results: There has recently been a remarkable increase in the number of studies from Korea, and the number of patients included in studies has increased since 2009. In most studies, the surgical procedures were longer, blood loss was reduced, and the number of retrieved lymph nodes was the same in the LTG group as in the open total gastrectomy group. The incidence of postoperative complications and that of inflammation during postoperative recovery were the same in these two groups., Conclusions: During LTG, the method used for esophagojejunostomy is important for surgical reliability and to reduce postoperative complications. There has been rapid development of new techniques from the level of esophagojejunostomy through a small skin incision to the high level of intracorporeal esophagojejunostomy using various techniques. A nationwide prospective phase II study is urgently needed to establish the value of LTG.

Objective: This retrospective study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy., Methods: Two cycles of a 3-week regimen of fluoropyrimidine S-1 (40 mg/m(2), orally, twice daily), together with cisplatin (60 mg/m(2), intravenously, day 8), were administered to patients, separated by a 2-week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n = 27). We retrospectively evaluated overall survival and prognostic factors in these patients., Results: Univariate analysis showed that positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after S-1 plus cisplatin chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor., Conclusion: After S-1 plus cisplatin neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results., (2015 S. Karger AG, Basel)

Background: The clinical significance of body mass index (BMI) on the surgical outcomes in gastric cancer patients still remains controversial., Methods: The subjects included 427 patients who underwent gastrectomy between January 2001 and December 2005. The patients were principally divided into 3 groups on the basis of BMI: low (<18.5 kg/m2), normal (≥18.5-<25.0 kg/m2) and high (≥25.0 kg/m2)., Results: The low-BMI patients had more advanced disease than the other patients. There were no statistically significant differences in the characteristics of the normal- and high-BMI patients. The operation time was longer in the high-BMI group, but there were no differences in terms of lymph node dissection and postoperative complications among these 3 groups. The overall survival and disease-specific survival of the low-BMI group were worse than the other 2 groups. These survival rates of high-BMI group tended to be better than those of the normal BMI group; however, it was not statistically different. A multivariate analysis of these survival rate showed that a low BMI was an independent predictor of a poor prognosis., Conclusions: A low-BMI was an independent factor of poor prognosis for overall and disease-specific survivals after surgery in Japanese patients with gastric cancer. A high-BMI was not a risk factor., (© 2015 S. Karger AG, Basel.)

Background: Accurate evaluation of the biological behavior of Gastrointestinal stromal tumor and careful selection of patients with a high risk for tumor recurrence are necessary. In the present study, we analyzed prognostic factors in patients with GIST., Patients and Methods: A total of 214 patients who had undergone curative resection of a localized primary gastric GIST without adjuvant therapy were enrolled in this retrospective study. Prognostic factors were analyzed. The growth pattern was classified as intramural, endoluminal, exoluminal, or mixed- type., Results: On univariate and multivariate analyses, recurrence was predicted by exoluminal or mixed-type (hazard ratio [HR]=3.7, p=0.043), tumor size of >3.5 cm (HR=7.1, p=0.01), and mitotic rate of >5/50 high-power fields (HR=7.9, p<0.001)., Conclusion: It is suggested that exoluminal or mixed-type is independently associated with recurrence of surgically resected gastric GIST in addition to tumor size and mitotic rate., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A 62-year-old woman, who had multiple pulmonary nodules noted 6 years earlier, and surgery for a gastrointestinal stromal tumor 2 years earlier, was found to have enlargement of her pulmonary nodules. Surgery was selected to make a definite diagnosis. Thoracoscopic segmentectomy of right segments 9 and 10 was performed, and pulmonary chondroma was diagnosed. Carney designated the combination of 3 rare soft tissue tumors (gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal paraganglioma) as a syndrome. This patient may have had an incomplete type of Carney's triad with 2 lesions in the stomach and lung., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Purpose: The combination of docetaxel and S-1 (DS) therapy is effective in patients with unresectable gastric cancer and is expected to be a regimen in neoadjuvant setting for advanced gastric cancer. This study was held to evaluate the efficacy and safety of DS followed by surgery., Methods: Patients with resectable gastric cancer received 2 courses of docetaxel 40 mg/m(2) on days 1, 15 and S-1 40 mg/m(2) bid orally on days 1-7, 15-21 every 4 weeks, followed by standard radical gastrectomy. Primary end point was the pathological response rate: rate of tumors in which one-third or more parts were affected., Results: Fourteen patients were enrolled. Thirteen (92.8 %) patients completed two courses of chemotherapy. Grade 3 adverse events were neutropenia in 3 (21.4 %) patients, anemia in 1 (6.2 %) patient and diarrhea in 1 (6.2 %) patient. There were no grade 4 adverse event and febrile neutropenia. All patients underwent R0 resection, and pathological response was found in 50.0 % of patients. There were no major surgical complications and no treatment-related mortality., Conclusions: The neoadjuvant chemotherapy with DS was effective for patients with locally advanced gastric cancer with manageable toxicities. Further study to confirm the usefulness of this regimen is needed.

Here, we report the case of a patient with advanced gastric cancer complicated by pyloric stenosis and direct invasion into the pancreas who underwent curative resection after bi-weekly S-1/docetaxel(DS)therapy after gastrojejunostomy. A 73-year-old man consulted a general practitioner because of indigestibility, and upper gastrointestinal endoscopy indicated gastric cancer. He was referred to our hospital. Gastric cancer, whole stomach tumor(LMU), 150×80 mm, Type 3, T4a(SE), N2, M0, stage III B was diagnosed, and surgery was performed. The tumor was seen to directly invade the pancreas and the middle colic artery intraoperatively, so only a gastrojejunostomy was performed. After the operation, the patient was treated with DS therapy for 13 courses, and the response was defined as non-complete response(CR)and non-progressive disease (PD). During the second laparotomy, a curative operation was performed via distal gastrectomy because frozen-section diagnosis revealed that no cancer cells were present at the oral margin. Postoperatively, the tumor was diagnosed as LM, 10× 7 mm, 10×2.5 mm, pType 4, pT2(MP), pN0, pM0, CY0, stage I B. The patient is now receiving S-1 adjuvant chemotherapy and is still alive 2 years and 4 months after the first operation.

Background: The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1(TS-1, an oral fluoropyrimidine) was effective as adjuvant chemotherapy for patients with pathological stage II or III gastric cancer who underwent curative gastrectomy. The objective of this study was to clarify the risk factors for recurrence in patients who received S-1 adjuvant chemotherapy., Patients and Methods: We retrospectively analyzed the factors predicting recurrence in 77 patients with stage II or III gastric cancer who received S-1 chemotherapy following R0 gastrectomy between April 2003 and October 2008., Results: The tumor diameter, macroscopic appearance, and presence of lymph node metastasis were significant factors predictive of recurrence identified by the univariate analysis. Moreover, the tumor diameter was an independent risk factor identified by the multivariate analysis., Conclusion: It is necessary to establish a chemotherapeutic regimen for patients with stage II/III gastric cancers with large tumor diameter.

Overexpression of atypical protein kinase Cλ/ι (aPKCλ/ι), a regulator of cell polarity, is frequently associated with the poor prognoses of several cancers, including gastric cancer. Recent studies revealed a molecular link between aPKC and KIBRA, an upstream regulator of tumor suppressor Hippo pathway that regulates cell proliferation and apoptosis. Further, KIBRA directly inhibits the kinase activity of aPKC to regulate epithelial cell polarity. These observations suggest that the KIBRA-aPKC connection plays a role in cancer progression; however, clinical significance of the correlation between these factors remains unclear. Here we examined the correlation between KIBRA/aPKCλ/ι expression, as detected by immunohistochemistry, and clinicopathological outcomes in 164 gastric cancer patients using Fisher's exact test and Kaplan-Meier log-rank test. We found an intimate correlation between the expression level of KIBRA and aPKCλ/ι (P = 0.012). Furthermore, high expression of KIBRA is correlated with lymphatic (P = 0.046) and venous invasion (P = 0.039). The expression level of KIBRA by itself did not correlate with the prognosis; however, high expression of KIBRA in low aPKCλ/ι-expressing gastric cancer correlated with disease-specific (P = 0.037) and relapse-free survival (P = 0.041) by Kaplan-Meier with log-rank test and higher lymphatic invasion cases by Fisher's exact test (P = 0.042). Furthermore, overexpression of the aPKC-binding region of KIBRA disrupted tight junctions in epithelial cells. These results suggest that high expression of KIBRA in low aPKC-expressing cells causes massive loss of aPKC activity, leading to loss of polarity and invasiveness of gastric cancer cells., (© 2012 Japanese Cancer Association.)

Background/aim: This study assessed the toxicity and activity of biweekly docetaxel and S-1 combination therapy in elderly patients with advanced gastric cancer., Patients and Methods: One-hundred and thirteen patients were enrolled: 35 were 75 years old or more. The objective response rate, toxicity, progression-free survival (PFS), and overall survival (OS) were compared., Results: Dose reduction was significantly frequent in the elderly group (24/35 versus 25/78, p<0.001). The overall response rate was 54.9%. Out of these, 18 (15.9%) underwent gastrectomy (13 R0 gastrectomy). The median OS was 17.3 months and the median PFS was 8.0 months. Neutropenia was the most frequently observed hematological toxicity at grade 3 and 4 (34.5%), followed by leukopenia (24.8%). Most non-hematological toxicities were of grade 1 or 2. There were no significant differences in overall response rate, median OS, median PFS, or toxicities between the two groups., Conclusion: This combination offers favourable survival benefits with controllable tolerance for therapy of AGC in the elderly.

To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy, a dose-escalating phase I study was conducted. Cohorts of patients were treated with escalating doses of DOC (starting at 20 mg/m² per week with 5 mg/m² increments) and a fixed dose of CDDP (25 mg/m²). Drugs were administered on days 1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were performed, and the mean number of courses was 5.3. Two of the four patients at dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3 anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined as 25 mg/m². There is a need for a phase II clinical trial using this regimen in patients with S-1-refractory stage II/III gastric cancer.

Background/aims: Effectiveness of gastric emptying after pylorus-preserving gastrectomy (PPG) remains unclear and a method for continuous assessment is needed. We assessed post-PPG gastric emptying with a continuous real-time ¹³C breath test (BreathID system, Oridion, Israel)., Methodology: Gastric emptying function was assessed by ¹³C breath test in 12 post-PPG patients and 9 post-distal gastrectomy (DG) patients. Continuous ¹³C-acetic acid breath test was performed using the BreathID system. Endoscopic study was also completed., Results: Diarrhea was significantly less common in PPG than DG patients (p=0.021). No other questionnaire items and endoscopic findings showed a significant difference. In the ¹³C-acetic acid breath test, the gastric emptying coefficient (GEC) was significantly greater in PPG than DG patients (p=0.025). No other test parameters showed a significant difference., Conclusions: Emptying function in the remnant stomach was assessed successfully by the continuous ¹³C-acetic acid breath test. A greater GEC suggested better gastric emptying in PPG patients.

Background: The aim of this study was to clarify the technical feasibility and oncological efficacy of laparoscopy-assisted gastrectomy (LAG) for gastric cancer compared with open gastrectomy (OG)., Methods: Between April 2002 and March 2008, a series of 623 patients with gastric cancer underwent R0 gastrectomy (314 LAG patients and 309 OG patients). Age, gender, lymph node dissection, and pathological stage were matched by propensity scoring, and 212 patients (106 LAG and 106 OG) were selected for analysis after the exclusion of 40 patients who had proximal gastrectomy. Intraoperative factors, postoperative morbidity, long-term quality of life (QOL), and survival were evaluated. Moreover, these outcomes were also compared between the laparoscopy-assisted total gastrectomy (LATG) and the open total gastrectomy (OTG)., Results: There was no significant difference in preoperative characteristics between the two patient groups. Regarding intraoperative characteristics, blood loss was significantly lower in the LAG group (143 ml) than in the OG group (288 ml), while operation time was significantly longer in the LAG group (273 min) than the OG group (231 min). The degree of lymph node dissection and number of retrieved lymph nodes did not differ between the two groups. There were no significant differences in postoperative courses or overall and disease-specific survival (89.8% vs. 83.6%, P = 0.0886; 100% vs. 95.2%, P = 0.1073) except time to first flatus and time to use of nonsteroidal anti-inflammatory derivatives between the two groups. Significantly fewer patients felt wound pain in the LAG group 1 year after surgery. Analyses between the LATG and OTG groups showed similar results., Conclusions: LAG for gastric cancer may be both feasible and safe. However, it will be necessary to conduct a well-designed randomized controlled trial comparing short-term and long-term outcomes between LAG and OG in a larger number of patients.

Background/aims: Single-port and reduced-port laparoscopic surgeries are performed as a less invasive form of surgery than conventional laparoscopy. In this study, short-term patient outcomes were compared between reduced-port laparoscopic distal gastrectomy (RPLDG) and conventional laparoscopy-assisted distal gastrectomy (LADG) to evaluate the feasibility of RPLDG for gastric cancer., Methods: Between August 2010 and July 2011, 38 patients underwent LADGs that were performed by a single surgeon. Of these, 20 patients underwent RPLDG, and 18 patients underwent conventional LADG. Short-term outcomes were compared between the two groups., Results: Surgical procedures, total operation time (278.8 versus 228.7 min, p = 0.0002) and time for lymph node dissection (181.3 versus 136.3 min, p = 0.0001) were significantly longer in the RPLDG group compared with the LADG group, while the volume of blood loss during reconstruction was reduced (17.5 versus 49.6 ml, p = 0.0019). Cosmetic satisfaction in the RPLDG group showed significant superiority over that in the conventional LADG group (p = 0.0252)., Conclusion: RPLDG was shown to be an acceptable and satisfactory procedure for the treatment of gastric cancer. To confirm the feasibility of this surgical procedure, it is necessary to conduct a well-designed randomized controlled study comparing RPLDG and conventional LADG in many patients., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: This study was conducted to determine the prognostic value of the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score composed of C-reactive protein and albumin, for patients with advanced cancer., Methods: A total of 83 advanced gastric cancer patients receiving biweekly docetaxel/S-1 treatment (DS) were included in the study. To identify the value of GPS as prognostic factor for disease-specific survival (DSS) and progression-free survival (PFS), univariate and multivariate analyses were performed., Results: Unresectable tumors were observed in 78 patients and recurrent tumors were detected in 5 patients. Of these, 12 patients underwent gastrectomy. There were significant correlations between the GPS and the neutrophil/lymphocyte ratio. Univariate analysis revealed that the GPS, Eastern Cooperative Oncology Group performance status and gastrectomy after DS treatment significantly affected prognosis. Multivariate analysis showed that the GPS, age and gastrectomy independently influenced DSS, and that the GPS and gastrectomy also influenced PFS. Multivariate analysis restricted to patients without gastrectomy showed that the GPS and age independently affected DSS, and that the GPS influenced PFS., Conclusion: In the low GPS group, it may be possible to obtain favorable outcomes by chemotherapy in advanced gastric cancer patients. However, a well-designed prospective trial in a large patient cohort is required to corroborate the prognostic value of the GPS., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer., Methods: Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0-2 and no prior chemotherapy history were eligible for inclusion (n = 45). Patients received a total of 215 treatment courses (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was administered intravenously on days 1 and 15., Results: We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3 months, the median time to progression was 6.9 months, and the median duration of response in 26 patients was 8.0 months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths., Conclusions: S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.

Background: Laparoscopy-assisted total gastrectomy (LATG) is not a commonly performed procedure due to the surgical difficulty associated with reconstruction. Although various reconstruction methods have been reported, a standard technique has not yet been established. In this study, we compared the short-term outcomes of LATG reconstructed by mini-laparotomy and by the newly developed transorally inserted anvil (OrVil)., Methods: From April 2006, a series of 45 patients underwent LATG. Of these, 15 were reconstructed by mini-laparotomy and 30 by OrVil. Short-term outcomes were compared between the two groups., Results: Operation time was significantly shortened and intraoperative blood loss significantly reduced by the use of OrVil. The postoperative course, including morbidity, did not differ between the two groups., Conclusions: LATG using OrVil for the treatment of early gastric cancer is a technically feasible surgical procedure with sufficient lymph node dissection, satisfactory early recovery, and acceptable morbidity. It will be necessary to perform this novel technique in a large number of patients to confirm its feasibility.