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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.)

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.

We report the case of a 69-year-old man diagnosed with gastric cancer.The patient underwent distal gastrectomy(D2) and Billroth I reconstruction in March, 2010. Postoperative histopathological examination indicated M, Ant, Type 5, 100×50 mm, pap>por2>sig, T4aN3M0, pStage III C.We performed S-1 therapy as adjuvant chemotherapy.Abdominal CT showed para-aortic lymph node recurrence in February, 2015. Since HER2 protein was overexpressed in primary tumor immunostaining, he was treated with capecitabine plus CDDP plus trastuzumab therapy.After the chemotherapy, CEA levels decreased to the normal range and the enlarged lymph node was remarkably decreased in size in May, 2015.T he patient is alive 24 months after the chemotherapy with no evidence of recurrence.

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: 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.

A 75-year-old man admitted for left lateral abdominal pain was found to have advanced poorly differentiated gastric adenocarcinoma with abdominal para-aortic and Virchow's lymph node metastases, which was diagnosed to be clinical Stage IV (T3N3H0M1[LYM]). As curative surgery was not deemed possible, we started chemotherapy administration using S-1 (120mg/day)administered orally for 3 weeks and cisplatin(CDDP 100mg/body)administered intravenously on day 8. After 6 courses of chemotherapy, a CT scan showed that all lymph nodes metastases had disappeared, resulting in downstaging to clinical Stage II (T3[SE]N0H0P0M0). Thus, we performed total gastrectomy, lymph node dissection(D2), and splenectomy. Histological findings showed no residual tumor cells in any of the lymph nodes. However, cancer cells remained in the primary gastric lesion. The pathological response to chemotherapy was judged to be Grade 2. The patient has been recurrence-free for 5 years after surgery.

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.

A 77-year-old man underwent total gastrectomy with D1+ lymph node dissection after being diagnosed with cT4aN2M0, cStage ⅢB gastric cancer. Peritoneal dissemination was detected in the bursa omentalis. The pathological diagnosis after surgery was pT4aN3b (21/41) M1 (P1). He was treated with 6 courses of S-1 chemotherapy. Two years after surgery, upper gastrointestinal endoscopy revealed the presence of a tumor in the mid-thoracic esophagus. It was diagnosed to as metastatic esophageal cancer and treated with combination chemotherapy consisting of docetaxel (25 mg/m2, days 1, 8, 15) and cisplatin (25 mg/m2, days 1, 8, 15) in a 28-day cycle. A clinically complete response was observed after 5 courses of chemotherapy. Currently, the patient is alive with no signs of recurrence 12 months after the initial recurrence.

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: 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)

We retrospectively studied the clinical efficacy and safety of the combination therapy with low-dose cis-diamminedichloroplatinum ( CDDP) and irinotecan hydrochloride(CPT-11)as a second- or third-line chemotherapy in 41 patients with advanced and recurrent gastric cancer. Low-dose CDDP (20mg/m²) and CPT-11 (80 mg/m²) were administered intravenously once every 2 or 3 weeks. The patients comprised 31 men and 10 women, with ages ranging from 42 to 81 years (mean, 67.4 years). The overall treatment response rate was 12%, including 5 partial responses but no complete response. The mean survival time was 8 months, and the disease-free survival time was 3.7 months from the start of the regimen. The median number of treatment cycles was 7.1 (range, 1.0-26.0). The most common grade 3/4 toxicity was neutropenia (2 cases), followed by dehydration (1 case) and allergy (1 case). Our data suggest that the combination of low-dose CDDP and CPT-11 has mild therapeutic toxicities and may effectively prolong the median survival time in patients with advanced and recurrent gastric cancer.

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.)

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.

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.

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.

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.)

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: 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.

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.

Background and Objectives: This study compared surgical outcomes between patients undergoing laparoscopy-assisted distal gastrectomy (LADG) and those undergoing open distal gastrectomy (ODG) from the viewpoint of obesity., Methods: Between June 2002 and May 2008, 146 patients with preoperatively diagnosed early gastric cancer who underwent LADG (n = 90) or ODG (n = 56) were enrolled in this study and compared in terms of clinicopathological findings and operative outcome. The visceral fat area (VFA) and subcutaneous fat area (SFA) were assessed as identifiers of obesity using FatScan software. The relationship between obesity and operative outcomes after LADG and ODG was evaluated., Results: There were no significant correlations between intraoperative blood loss (IBL) and any obesity-related factors, or between operation time (OT) and any obesity-related factors in the LADG group. There was a significant correlation between IBL and BMI (r = 0.486, P = 0.0001), IBL and VFA (r = 0.456, P = 0.0003), IBL and SFA (r = 0.311, P = 0.0193), OT and BMI (r = 0.406, P = 0.0017), OT and VFA (r = 0.314, P = 0.0178), and between OT and SFA (r = 0.382, P = 0.0034) in the ODG group., Conclusions: LADG may be a useful operative manipulation that is not influenced by obesity, whereas ODG may be influenced by obesity even after reaching the surgical plateau., ((c) 2010 Wiley-Liss, Inc.)

Background: The significance of hepatic resection for liver metastasis after gastric cancer is not well established. This study aimed to evaluate the effect of hepatic resection in such patients., Patients and Methods: A retrospective analysis was performed on the outcome of 63 patients with liver metastases without other non-curative factors of gastric cancer who underwent gastrectomy with or without hepatic resection., Results: Overall 1-, 3-, and 5-year survival rates were 61.9%, 17.2%, and 10.3%, respectively, with a median survival time of 16 months. This increased to 82.3%, 46.4%, and 37.1%, respectively, with a median survival time of 31.2 months in patients who underwent hepatic resection. Multivariate analysis showed that hepatic resection was an independent prognostic factor. Moreover, unilobar liver metastases significantly influenced favorable prognosis in patients receiving hepatic resection by univariate analysis., Conclusion: In patients with liver metastases, hepatic resection may be a therapeutic option in the presence of unilobar liver metastases.

Background: Patients with stage I gastric cancer often suffer from tumor recurrence despite a generally favorable operative outcome. It is therefore important to determine the prognostic factors in order to improve such outcomes., Methods: Between April 1985 and March 2000, a total of 1,880 patients with histologically proven stage I gastric cancer were included in this study. Operative outcomes (survival time, prognostic factors, pattern of recurrence) were evaluated in these patients., Results: Multivariate analysis in patients with all stage I gastric cancer revealed that depth of invasion, lymph node metastasis, and lymphovascular invasion independently influenced prognosis. Moreover, advanced age was selected as an independent prognostic factor in patients with stage IA, and lymphovascular invasion in patients with stage IB gastric cancer by multivariate analyses. The 5-year survival rates in stage T1N1 patients with moderate to severe lymphovascular invasion, T2N0 with moderate to severe lymphovascular invasion, and II were 95.1%, 83.5%, and 76.9%, respectively. There was a significant difference in survival time between stage T1N1 and II (P = .0189) but not between stage T1N1 and T2N0 or stage T2N0 and II., Conclusion: T2N0 gastric cancer patients with moderate to severe lymphovascular invasion may be suitable candidates for adjuvant chemotherapy., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: The atypical protein kinase C lambda/iota (aPKClambda/iota) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKClambda/iota has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKClambda/iota in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKClambda/iota expression and the clinicopathological features of gastric cancer., Patients and Methods: Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKClambda/iota and E: -cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival., Results: Overexpression of aPKClambda/iota protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKClambda/iota was stronger in gastric adenocarcinoma of intestinal type than diffuse type (p = 0.036), but was not correlated with E: -cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKClambda/iota overexpression were prognostic factors for disease recurrence., Conclusions: Our results suggested that aPKClambda/iota overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKClambda/iota is also likely to be a novel therapeutic target for gastric cancer.

A 70-year-old male patient had advanced gastric cancer with severe lymph node metastasis. He was treated by combination chemotherapy of S-1 120 mg/body (1-week administration and 1-week rest)and docetaxel (DOC) 40 mg/body( day 1 and 15). After 2 courses of treatment, the primary lesion was remarkably improved and para-aortic lymph nodes disappeared by CT scan, so we diagnosed it as a partial response (PR). Anemia (WHO grade 3) was observed as toxicity and treated with transfusion. This regimen could be performed on an outpatient basis for over 2 years, and the response was maintained on CT and endoscopic examination after 20 courses of treatment. The biweekly docetaxel and S-1 combination chemotherapy was thought to be an effective method as chemotherapy for an outpatient with advanced gastric cancer.

Background: Some studies have found high incidences of intraoperative and postoperative complications for patients with gastric cancer. To determine the predictive factors for the surgical complications of laparoscopic gastric surgery, surgical outcomes were evaluated., Methods: Between April 2002 and December 2007, 152 patients with preoperatively diagnosed early gastric cancer who underwent laparoscopy-assisted distal gastrectomy (LADG) were enrolled. Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan software. The predictive factors for surgical complications of LADG were evaluated by univariate and logistic regression analyses., Results: Of 152 patients, conversion to open surgery due to uncontrollable bleeding was observed in nine male patients, and postoperative complications were detected in seven male and one female patient (four anastomotic leakage, two intraabdominal abscess, one pancreatic fistula, and one lymphorrhea). High body mass index (BMI) and high VFA independently predicted conversion to open surgery and postoperative complications. VFA was significantly higher, operation time was longer, blood loss was greater, and SFA was lower in male than in female patients, whereas no significant difference was observed in BMI between male and female patients., Conclusions: High BMI and high VFA can predict technical difficulties during laparoscopic gastric surgery and postoperative complications. Particularly, LADG should be performed cautiously to prevent surgical complications for male patients with high VFA. Predictive impact of VFA should be further determined in a larger set of patients.

Background: We retrospectively evaluated the efficacy of weekly paclitaxel therapy as second-line treatment for patients with advanced gastric cancer that was refractory to S-1., Patients and Methods: In total, 33 patients received intravenous paclitaxel (80 mg m(-2)) on days 1, 8 and 15 as part of a 4-week cycle., Results: Eight patients showed a partial response, 11 showed stable disease and 14 showed disease progression. In total, 171 courses (mean=5.2; range=3-16) were administered. Thirteen cases subsequently underwent third-line treatment. The median survival time and time to progression from the time of second-line treatment was 8.0 months and 4.2 months, respectively. The most common haematological toxicities were leukopenia and neutropenia. Non-haematological toxicities were generally mild to moderate and controllable., Conclusion: This study showed favourable therapeutic outcomes for advanced gastric cancer patients. However, it will be necessary to confirm the advantages of paclitaxel treatment for S-1-refractory advanced gastric cancer in a larger population.

Background: To date, it has been unclear whether laparoscopy-assisted distal gastrectomy (LADG) is a suitable treatment for elderly patients with early gastric cancer. This study retrospectively compared surgical outcomes between elderly and nonelderly patients with gastric cancer., Methods: The study group was comprised of 211 patients who underwent distal gastrectomy between April 2000 and March 2007. Of these, 130 patients (26 aged >or=75 years and 104 aged <75 years) underwent LADG, and the remaining 81 patients underwent conventional open distal gastrectomy (ODG). Short- and long-term patient outcomes were evaluated., Results: The operation time was significantly longer in the LADG group than in the ODG group (262.6 versus 234.3 min, p = 0.005), but the other short-term outcomes did not differ between the two groups. When performed by an experienced surgeon, blood loss was significantly reduced, while operation time for LADG was similar to that for ODG. Within the LADG group, incidences of comorbid disease and lymph-node metastasis were significantly greater, the histological tumor type was significantly more differentiated, and the macroscopically depressed tumor type was less common in elderly patients. However, the incidence of postoperative morbidity did not differ between the elderly and nonelderly groups (11.5% versus 3.8%, p = 0.1201), and there was no significant difference in postoperative course. Logistic regression analysis showed that body mass index, but not chronological age, was an independent predictive factor of postoperative morbidity (odds ratio = 3.674, p = 0.045). There were no significant differences in overall or disease-specific survival between elderly and nonelderly patients., Conclusion: LADG is an effective treatment for elderly patients with early gastric cancer if it is performed by an experienced surgeon. A high-volume study is needed to confirm this rationale.

Background: The aim of this study was to determine the influence of stage migration on the outcomes of D2 gastrectomy compared with D3 gastrectomy in advanced gastric cancer., Methods: A series of 580 advanced gastric cancer patients (430 D2 gastrectomy and 150 D3 gastrectomy) were registered. The incidence of stage migration and the surgical results of D2 and D3 gastrectomy were compared., Results: The incidence of N-stage migration was 22.7% and that of pathological stage was 20.7%. Stage-specific survival times of simulated D2 gastrectomy and real D2 gastrectomy were equal. In patients with pN2 tumors measuring 50 to 100 mm in diameter, there was a significant difference in survival between D2 and D3 gastrectomy. However, no difference was observed between D2 and simulated D2 gastrectomy., Conclusions: Because there was a high incidence of stage migration in patients after D3 gastrectomy, it may be more feasible to validate comparisons between different levels of lymph node dissection in a randomized controlled trial.

Background/aims: The purpose of this study was to evaluate and compare the use of 4.8-mm and 3.8-mm staples in gastric resection., Methodology: A series of 60 patients underwent distal or proximal gastrectomy. A 4.8-mm GIA universal stapler was randomly assigned for use in 50% of the patients and a 3.5-mm GIA universal stapler was assigned for use in the remaining 50%., Results: Bleeding was observed in 20 patients (12 in the 4.8-mm group and eight in the 3.5-mm group). In the 4.8-mm group, bleeding was less frequent in patients with a stomach wall thickness of 7.0-9.0mm. In the 3.5-mm group, bleeding was less frequent in patients with a stomach wall thickness of 5.0-7.0mm. Inappropriate staple formation was observed in patients with thick stomach walls in each group., Conclusions: The appropriate staple size for gastric surgery may depend on the thickness of the stomach wall.

Background: The aim of this study was to evaluate the prognostic value of tumor diameter in gastric cancer., Methods: The study group comprised a series of 1215 patients who underwent curative gastrectomy. The appropriate tumor diameter cutoff value was determined. Prognostic factors were evaluated by univariate and multivariate analyses., Results: The tumor diameter cutoff value was 100 mm. Multivariate analysis showed that tumor site, macroscopic appearance, tumor diameter, depth of invasion, and presence of lymph node metastasis independently affected prognosis in all patients. Multivariate analysis of patients with larger tumors identified depth of invasion as an independent prognostic factor. A comparison between patients with smaller and larger tumors showed marked differences in the survival of those with stage II, IIIA, and IIIB tumors. A comparison of clinicopathological factors between stage II and III patients revealed that tumors occupying the entire stomach, ill-defined, undifferentiated, and serosa-penetrating tumors, and peritoneal metastases were far more frequent in patients with larger tumors., Conclusions: Tumor diameter in gastric cancer is a reliable prognostic factor that might be a candidate for use in the staging system. To improve outcomes for patients with tumors >/=100 mm in diameter, it is necessary to establish therapeutic strategies for peritoneal metastasis, particularly in stage II and III tumors.

Background: Docetaxel and S-1 are novel antitumour chemotherapeutic agents with distinct toxicities. Here a phase I study of combined docetaxel and S-1 therapy for advanced gastric cancer is reported., Patients and Methods: The study group comprised 21 patients who received at least two courses of treatment. Intravenous docetaxel was administered with dose escalation from 20-45 mg/m2 depending on the dose-limiting toxicity (DLT) on days 1 and 15, and oral S-1 (BSA < 1.25 m2, 80 mg/day; 1.25 < or = BSA < 1.50 m2, 100 mg/day; 1.50 m2 < or = BSA, 120 mg/day) was administered on days 1-7 and 15-21., Results: The maximum tolerated dose of docetaxel was 45 mg/m2 and the DLT was defined as neutropenia. The recommended docetaxel dose was identified as 40 mg/m2. The response rate (including partial responses) was 57.1%. Five cases showed no change and four showed progressive disease after two courses of treatment. The mean survival rate was 15 months., Conclusion: A phase II clinical trial is required to confirm these results.

An assessment of the learning curve of laparoscopy-assisted distal gastrectomy (LADG) might encourage its worldwide spread among inexperienced surgeons. One hundred sixty-seven patients with early gastric cancer were enrolled in this study: 67 underwent conventional open distal gastrectomy and 100 underwent LADG after classification into 5 groups of 20 according to the surgeon's level of experience. Patient characteristics and operative findings were compared between groups. Operation time was significantly longer, time to first flatus earlier, and blood loss reduced in the LADG groups compared with the open distal gastrectomy group. Surgeons with experience of 60 cases performed operations of similar times in both groups, and blood loss decreased with experience of 20 cases. There was no operative conversion, the frequency of nonsteroidal anti-inflammatory drugs administered were significantly less, and length of hospital stay were shorter by surgeons with experience of 60 cases. LADG is a technically feasible surgical procedure, depending on the surgeon's technical proficiency. Experience of at least 60 cases of LADG seems to result in satisfactory patient outcomes.

The metastatic lymph-node ratio has important prognostic value in gastric cancer; this study focused on its significance in early gastric cancer. In total, 1,472 patients with early gastric cancer underwent curative gastrectomy between 1992 and 2001. Of these, 166 (11.3%) had histologically proven lymph-node metastasis. Prognostic factors were identified by univariate and multivariate analyses. Metastasis was evaluated using the Japanese Classification of Gastric Carcinoma (JGC) and the Union Internationale Contre le Cancer/Tumor, Node, Metastasis (UICC/TNM) Classification. The metastatic lymph-node ratio was calculated using the hazard ratio. The cut-off values for the metastatic lymph-node ratio were set at 0, <0.15, >or=0.15 to <0.30, and >or=0.30. The numbers of dissected and metastatic lymph nodes were correlated, but the number of dissected lymph nodes and the metastatic lymph-node ratio was not related. The JGC and UICC/TNM classification demonstrated stage migration and heterogeneous stratification for disease-specific survival. The metastatic lymph-node ratio showed less stage migration and homogenous stratification. The metastatic lymph-node ratio may be a superior method of classification, which provides also accurate prognostic stratification for early gastric cancer patients.

Background: The efficacy of palliative gastrectomy for incurable advanced gastric cancer remains debatable., Patients and Methods: The study group comprised a series of 164 patients who had undergone palliative gastrectomy. Survival and prognostic factors were evaluated by univariate and multivariate analyses., Results: The median survival time was 9 months. Univariate analysis identified the following as factors that adversely affected survival: larger and deeper undifferentiated tumors; peritoneal, hematogenous, or remaining lymph-node metastasis; a large number of non-curative factors; less extensive lymph-node dissection; and an absence of chemotherapy. The Cox proportional regression hazard model recognized histological type, hematogenous metastasis, peritoneal metastasis and chemotherapy as independent factors. Moreover, the number of non-curative factors independently affected the disease-specific survival. In patients with a single non-curative factor, histological type and adjuvant chemotherapy were independent prognostic factors., Conclusion: A randomized controlled study should be conducted in advanced gastric cancer patients with a single non-curative factor to confirm the usefulness of palliative gastrectomy followed by chemotherapy shown here.

Previous reports have suggested that splenectomy treatment of gastric carcinoma of the cardia results in poor patient outcome, but the reason for this is unclear. This study aimed to clarify the impact of splenectomy for gastric carcinoma patients. A total of 118 patients with gastric carcinoma of the cardia were enrolled in this study. The characteristics of patients with lymph node metastasis at the splenic hilum were determined, and the effects of lymph node dissection or splenectomy on postoperative morbidity, mortality, and pattern of recurrence were evaluated. Advanced tumors were common in patients with lymph node metastasis at the splenic hilum, Siewert type III, greater curvature sites, larger and deeper tumors, multiple metastatic lymph nodes, and high incidences of para-aortic lymph node metastasis frequently observed. The effectiveness of lymph node dissection of the splenic hilum was low and equal to that of dissection of the para-aortic lymph nodes. Postoperative morbidity, as represented by pancreatic fistula, was high following splenectomy or pancreaticosplenectomy, but patient mortality did not occur. Hematogenous metastasis was common, as well as peritoneal metastasis after curative gastrectomy. Splenectomy should be limited in those patients with gastric cardia tumors invading the spleen or with metastatic bulky lymph nodes extending to the spleen.

Background: The aim of this study was to clarify the lymph node status in patients with submucosal gastric cancer., Methods: Between April 1994 and December 1999, 615 patients with histologically proven submucosal gastric cancer who underwent curative resection were included in this study. The results of the surgery and predictive factors for lymph node metastasis were evaluated by univariate and multivariate analyses. The accuracy of the predictive factors was assessed in a second population of a further 186 patients., Results: Lymph node metastasis was observed in 119 patients (19.3%). Multivariate analysis showed that pathologic tumor diameter (> or = 20 mm) and lymphatic invasion were independent predictive factors for lymph node metastasis. The incidence of lymph node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors < 20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion. Among patients with a tumor < 20 mm in diameter, the incidence of lymph node metastasis was significantly reduced in those with a differentiated tumor: 4.2% (4 of 95). These results were almost identical to those observed in the second population., Conclusions: Lymph node status can be accurately predicted on the basis of pathologic tumor diameter < 20 mm, lymphatic invasion (absence), and histological type (differentiated) in patients with submucosal gastric cancer. Less extensive surgery for these patients might be reconsidered after confirmation of the reproducibility of the results of this study by an appropriately designed prospective clinical trial.

Gastric carcinoma is relatively rare in patients under the age of 40. This study was undertaken to clarify the clinicopathological characteristics and surgical outcomes of gastric carcinoma in younger patients compared with those of middle-aged patients. The surgical results from 131 younger patients (aged < or = 40 years) and 918 middle-aged patients (aged 55-65 years) were compared retrospectively. Female gender, undifferentiated tumor type and lymphatic invasion were significantly more common in the younger patients. Survival time did not differ between the two groups. The depth of tumor invasion was the only prognostic factor in younger patients, whereas macroscopic appearance, tumor diameter, depth of invasion, lymph node metastasis, and venous invasion were all significant prognostic factors in middle-aged patients. Peritoneal recurrence was significantly more common in younger patients. A family history of gastric adenocarcinoma was observed in 25.9% of younger patients, but this did not affect survival outcomes. As depth of invasion affects prognosis independently, and peritoneal metastasis is the predominant pattern of recurrence, it is essential to establish an optimal prophylactic treatment for peritoneal metastasis to improve surgical outcomes in younger patients with advanced gastric cancer.