Impact of a board certification system and adherence to the clinical practice guidelines for gastric cancer on risk-adjusted surgical mortality after distal and total gastrectomy in Japan: a questionnaire survey of departments registered in the National Clinical Database.

PURPOSE: The relationship between board certification, clinical guideline implementation, and quality of gastric cancer surgery remains unclear. METHODS: A web-based questionnaire survey was administered to departments registered in the National Clinical Database (NCD) of Japan between October 2014 and January 2015. Quality indicators (QIs) based on the Donabedian model were evaluated. Structural QIs (e.g., affiliations with academic societies and board certifications) and process QIs (adherence to clinical practice guidelines for gastric cancer) were assessed using risk-adjusted odds ratios (AORs) for surgical mortality. Multivariable logistic regression models with a generalized estimating equation were used. RESULTS: A total of 835 departments performing 40,992 distal gastrectomies and 806 departments performing 19,618 total gastrectomies responded. Some certified institutions and physicians showed significant associations, with lower AORs for surgical mortality. Important process QIs included pre- and postoperative abdominal CT scanning, endoscopic resection based on progression, curative resection with D2 dissection for advanced gastric cancer, laparoscopic surgery, and HER2 testing for patients with unresectable recurrent gastric cancer. CONCLUSIONS: Multiple structural and process QIs are associated with surgical mortality after gastrectomy in Japan. Measuring and visualizing QIs may enhance healthcare improvements.

An integrated analysis of two phase II trials (JCOG0001 and JCOG0405) of preoperative chemotherapy followed by D3 gastrectomy for gastric cancer with extensive lymph node metastasis.

BACKGROUND: Gastric cancer with extensive lymph node metastasis is commonly regarded as unresectable, while preoperative chemotherapy followed by gastrectomy has been tested since 2000 in JCOG (JCOG0001 and JCOG0405). The survivals were quite different between the trials despite the similar eligibility criteria. The aim of this study was to investigate if survival is still better in JCOG0405 after adjusting baseline factors and if there is any subset of patients who benefit more from either treatment. METHODS: Eligibility criteria for both trials included histologically proven gastric adenocarcinoma; bulky nodal involvement around the celiac artery and its major branches (bulky N) and/or para-aortic lymph node (PAN); cM0 (except PAN); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Patients received two or three cycles of preoperative chemotherapy of irinotecan plus cisplatin in JCOG0001, or S-1 plus cisplatin in JCOG0405, followed by D3 gastrectomy. Multivariable analysis for overall survival adjusting baseline and treatment factors was performed with the Cox regression model. RESULTS: After adjusting baseline factors, S-1 plus cisplatin was superior to irinotecan plus cisplatin for overall survival (HR = 0.39: 95% CI 0.22-0.67). The 5-year overall survival was poor for patients with bulky N+/PAN+ (19.2%) compared with bulky N+/PAN- (50.7%) or bulky N-/PAN+ (43.5%). CONCLUSIONS: S-1 plus cisplatin was shown to be a favorable preoperative treatment for gastric cancer with extensive lymph node metastasis by multivariable analysis, while poor prognosis in patients having both bulky N+ and PAN+ may necessitate further treatment improvement.

Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial.

Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m2 and intravenous paclitaxel 50 mg/m2 on days 1 and 8 plus S-1 80 mg/m2 per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m2 per day on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P = .080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P = .008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.

Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007).

BACKGROUND: The aim of this retrospective study was to investigate the tumor characteristics, surgical details, and survival distribution of surgically resected cases of gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. METHODS: Data from 118,367 patients with primary gastric carcinoma who underwent resection between 2001 and 2007 were included in the survival analyses. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The median age of the patients was 67 years. The proportions of patients with pathological stage (Japanese Gastric Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%, 11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who were treated by resection was 71.1%. The 5-year overall survival rates of patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were 91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease-specific survival rates in the patients with pT1 (mucosa) disease after D1+ dissection of lymph node station no. 7 (D1 + α), D1+ dissection of lymph node station nos. 7, 8, and 9 (D1+ ß), and D2 lymphadenectomy were 99.4%, 99.6%, and 99.1% respectively. The 5-year disease-specific survival rates in the patients with pT1 (submucosa) disease after D1 + α, D1 + ß, and D2 lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. CONCLUSION: Detailed analyses of the data from more than 100,000 patients show the recent trends of the outcomes of gastric cancer treatment in Japan and provide baseline information for use by medical communities around world.

Gastric cancer treated by endoscopic submucosal dissection or endoscopic mucosal resection in Japan from 2004 through 2006: JGCA nationwide registry conducted in 2013.

BACKGROUND: The Japanese Gastric Cancer Association (JGCA) initiated a new nationwide gastric cancer registry in 2008 and reported the treatment outcomes of patients with primary gastric cancer who underwent surgical therapy in 2001 and 2003. However, the outcomes of endoscopic therapy have not been reported yet. METHODS: The JGCA conducted a retrospective nationwide registry in 2013 to investigate the short-term and long-term outcomes of endoscopic mucosal resection or endoscopic submucosal dissection in patients with gastric cancer treated from January 2004 through December 2006. This registry used a computerized database with terminology in accordance with the JGCA classification (13th and 14th editions) and the Japanese Gastric Cancer Treatment Guidelines from 2010. RESULTS: Accurate data on 12,647 patients were collected from 126 participating hospitals and analyzed. The treatment procedure was endoscopic submucosal dissection in 81% of the patients and endoscopic mucosal resection in 19%. En bloc and R0 resections were achieved in 89% and 79% of the patients respectively. The total proportion of patients who underwent curative resection was 69.2%; 43.8% of patients underwent curative resection for absolute indication lesions, and 25.4% underwent curative resection for expanded indication lesions. Emergency surgery was performed to treat bleeding or perforation in very few patients (0.3% and 0.4% respectively). The 5-year follow-up rate after endoscopic resection was 70%. The 5-year overall survival rate was 91.6% in patients with absolute indications and 90.3% in patients with expanded indications after curative resection and 86.5% in patients who underwent noncurative resection. The 5-year disease-specific survival rates were 99.9%, 99.7%, and 98.7% in patients with absolute indications who underwent curative resection, patients with expanded indications who underwent curative resection, and patients who underwent noncurative resection respectively. CONCLUSION: Endoscopic resection of gastric cancer resulted in favorable short-term and long-term outcomes nationwide in Japan. Further efforts to increase the follow-up rate are needed.

Randomized Controlled Trial to Evaluate Splenectomy in Total Gastrectomy for Proximal Gastric Carcinoma.

OBJECTIVE: To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer. BACKGROUNDS: Splenectomy in total gastrectomy is associated with increased operative morbidity and mortality, but its survival benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive. METHODS: We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%. RESULTS: Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67-1.16) (<1.21); thus, the noninferiority of spleen preservation was confirmed (P = 0.025). CONCLUSIONS: In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival.

A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002.

BACKGROUND: Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose. METHODS: Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1, S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %. RESULTS: Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9-67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52). CONCLUSIONS: Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.

Nomogram for 5-year relapse-free survival of a patient with advanced gastric cancer after surgery.

BACKGROUND: Prognoses vary substantially among patients with advanced gastric cancer following curative surgery. The aim of the current study was to develop and verify the validity of a novel nomogram that predicts the probability of 5-year relapse-free survival (RFS) in patients who underwent curative resection for stage II/III gastric cancer. MATERIALS AND METHODS: A nomogram to predict 5-year RFS following surgical resection of gastric cancer was constructed based on the data of patients who underwent surgery for primary gastric carcinoma at three institutions in Japan in January 2001-December 2006. Multivariate analysis using a Cox proportional hazards regression model was performed, and the nomogram's predictive accuracy (discrimination) and the agreement between observed outcomes and predictions (calibration) were evaluated by internal validation. RESULTS: Multivariate analyses revealed that age at operation, depth of tumor, tumor location, lymph node classification, and presence of combined resection were significant prognostic factors for RFS. In the internal validation, discrimination of the developed nomogram for 5-year RFS was superior to that of the American Joint Committee on Cancer TNM classification (concordance indices of 0.80 versus 0.67; P < 0.001). Moreover, calibration appeared to be accurate. Based on these results, we have created free software to more easily predict 5-year RFS. CONCLUSION: We developed and validated a nomogram to predict 5-year RFS after curative surgery for stage II/III gastric cancer. This tool will be useful for the assessing a patient's individual recurrence risk when considering additional therapy in clinical practice.

Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial).

BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.

Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101).

BACKGROUND: Human epidermal growth factor (HER) 2 positivity and its association with clinicopathological factors remain unclear in Japanese gastric cancer (GC) patients. We performed a prospective, multicenter, observational cohort study to evaluate HER2 protein expression and gene amplification in Japanese metastatic and recurrent GC patients, and explored its correlations with clinicopathological features. METHODS: HER2 protein expression and gene amplification were centrally assessed in formalin-fixed, paraffin-embedded GC tissue by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Patient information was collected, and associations between clinicopathological factors and HER2 positivity (IHC score 3+ and/or FISH positive) and low HER2 expression (IHC score 0/FISH positive or IHC score 1+/FISH positive) were examined. RESULTS: From September 2011 to June 2012, 1461 patients were registered across 157 sites, and the HER2 status of 1427 patients was evaluated. The rate of HER2 positivity was 21.2 %, whereas the rate of high HER2 expression (IHC score 2+/FISH positive or IHC score 3+) was 15.6 % and that of low HER2 expression was 7.0 %. Multiple logistic regression analysis identified intestinal type, absence of peritoneal metastasis, and hepatic metastasis as significant independent factors related to HER2 positivity. The intestinal type was confirmed to be the GC subtype predominantly associated with lower HER2 expression. Sampling conditions including number of biopsy samples, formalin concentration, and formalin-fixation time did not significantly affect HER2 positivity. CONCLUSIONS: HER2 expression in Japanese patients was comparable to that in other populations examined. Intestinal type was an independent factor related to HER2 positivity and low HER2 expression.

Follow-up after gastrectomy for cancer: the Charter Scaligero Consensus Conference.

PURPOSE: Presently, there is no scientific evidence supporting a definite role for follow-up after gastrectomy for cancer, and clinical practices are quite different around the globe. The aim of this consensus conference was to present an ideal prototype of follow-up after gastrectomy for cancer, based on shared experiences and taking into account the need to rationalize the diagnostic course without losing the possibility of detecting local recurrence at a potentially curable stage. METHODS: On June 19-22, 2013 in Verona (Italy), during the 10th International Gastric Cancer Congress (IGCC) of the International Gastric Cancer Association, a consensus meeting was held, concluding a 6-month, Web-based, consensus conference entitled "Rationale of oncological follow-up after gastrectomy for cancer." RESULTS: Forty-eight experts, with a geographical distribution reflecting different health cultures worldwide, participated in the consensus conference, and 39 attended the consensus meeting. Six statements were finally approved, displayed in a plenary session and signed by the vast majority of the 10th IGCC participants. These statements are attached as an annex to the Charter Scaligero on Gastric Cancer. CONCLUSION: After gastrectomy for cancer, oncological follow-up should be offered to patients; it should be tailored to the stage of the disease, mainly based on cross-sectional imaging, and should be discontinued after 5 years.

Efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin and S-1 for resectable locally advanced gastric cancer.

BACKGROUND: The prognosis for locally advanced gastric cancer (AGC) remains unsatisfactory, even with S-1 adjuvant chemotherapy. We investigated the efficacy of neoadjuvant chemotherapy consisting of docetaxel, cisplatin and S-1 (DCS). METHODS: We retrospectively reviewed 59 patients who underwent neoadjuvant DCS therapy for clinical stage III tumors or serosa-positive tumors between January 2009 and December 2013 at Niigata Cancer Center Hospital. The patients received S-1 (40 mg/m(2) bid) on days 1-14, and docetaxel (35 mg/m(2)) and cisplatin (35 mg/m(2)) on days 1 and 15 every 4 weeks. RESULTS: Forty-three patients (72.9 %) received two courses of DCS therapy, while 16 patients (27.1 %) received one course of treatment. The clinical response rate of the primary tumor was 74.6 %, and the disease control rate was 100 %. A pathological response, defined as one-third or more of the affected tumor, was observed in 71.2 % of patients. The common grade 3/4 adverse events from chemotherapy were leucopenia (16.9 %), neutropenia (44.1 %), febrile neutropenia (8.5 %), anemia (10.2 %), anorexia (8.5 %) and nausea (6.8 %). Postoperative complications occurred in 11 patients (18.6 %). There was no treatment-related mortality or reoperation. The 3- and 5-year overall survival rates were 88 and 68.6 %, respectively. Clinical responders had a significantly higher survival rate than non-responders. Multivariate analysis identified clinical response as the only independent prognostic factor. CONCLUSIONS: Neoadjuvant DCS therapy demonstrated a very high clinical and pathological response rate with acceptable toxicities. Therefore, this therapy may improve the prognosis of locally AGC.

[A Case of Abdominal Para-Aortic Lymph Node Recurrence of Gastric Cancer Treated with Radiotherapy, Surviving More Than 5 Years].

A 66-year-old man was diagnosed with advanced type 2 gastric cancer and underwent total gastrectomy. The pathological diagnosis was T3N2H0P0CY0M0, stage ⅢB gastric cancer. Consequently, the patient received adjuvant S-1 therapy for 12 months. Thirty months after the operation, para-aortic lymph node recurrence was evident by computed tomography (CT). As a result, combination chemotherapy with paclitaxel, 5-fluorouracil, and cisplatin was initiated. However, after three courses of chemotherapy, abdominal CT showed progressive disease of the recurrent lymph node. Thereafter, radiotherapy at a total dose of 56 Gy was performed. After the radiotherapy treatment, abdominal CT demonstrated a remarkable reduction of the recurrent lymph node. The patient remains alive, with no signs of relapse, 70 months later. Therefore, this case suggests that radiotherapy may represent an effective treatment for localized remote lymph node recurrence of gastric cancer.

Characteristics of neoplastic cardiac tamponade and prognosis after pericardiocentesis: a single-center study of 113 consecutive cancer patients.

BACKGROUND: Neoplastic cardiac tamponade (NCT) is a life-threatening complication of cancer. The interval between cancer diagnosis and NCT onset and the prognosis after pericardiocentesis may differ according to cancer type. METHODS AND RESULTS: We performed a retrospective study of 113 patients (54 % male) with NCT who underwent pericardiocentesis at Niigata Cancer Center Hospital between 1992 and 2013. Mean age at NCT was 61.2 years (range 15.9-94.8 years). The most common underlying cancers were lung cancer (59.2 %), breast cancer (21.2 %), lymphoma/leukemia (5.3 %), and gastric/esophageal cancer (5.3 %). The median time from cancer diagnosis to NCT onset was 9.0, 60.4, 5.6, and 8.0 months for lung cancer, breast cancer, lymphoma/leukemia, and gastric/esophageal cancer, respectively. Kaplan-Meier survival estimates were worse for breast cancer patients with NCT than for matched breast cancer patients without NCT (P < 0.0001). Median survival time after pericardiocentesis was 2.9, 4.2, 2.3, and 0.6 months for lung cancer, breast cancer, lymphoma/leukemia, and gastric/esophageal cancer, respectively; one-year survival after pericardiocentesis was 6.0, 16.7, 33.3, and 0 %, respectively. CONCLUSIONS: The interval between cancer diagnosis and NCT onset, the impact of NCT on prognosis, and the prognosis after pericardiocentesis differed according to cancer type. Healthcare practitioners caring for patients with NCT should recognize the differences between cancer types and customize their care accordingly.

Prognostic analysis of submucosa-invasive gastric cancer with lymph node metastasis.

BACKGROUND: The aims of this study were to identify prognostic factors of patients with submucosa-invasive (T1b) gastric cancer and to verify the validity of adjuvant chemotherapy for this disease. METHODS: We retrospectively examined the cases of 1,236 consecutive patients in our prospectively maintained database with T1b gastric cancer who underwent gastrectomy in 1995-2012. We used 11 clinicopathologic characteristics to identify prognostic factors by univariate and multivariate analyses. We compared the survival of the 160 node-positive T1b gastric cancer patients with that of 133 patients in the same database who had node-positive muscularis propria-invasive (T2) gastric cancer and had undergone gastrectomy without adjuvant chemotherapy during the same period, as a reference cohort. RESULTS: The 5-year overall survival rate was 91.4% for all 1,236 patients. Advanced age (hazard ratio [HR] 4.51; 95% confidence interval [CI] 3.26-6.24; P < .01), male sex (HR 2.26; 95% CI 1.56-3.26; P < .01), and the presence of lymph node metastasis (HR 1.89; 95% CI 1.33-2.70; P < .01) were independent prognostic factors. The 5-year overall survival rates were 92.5% in node-negative patients, 84.5% in patients with 1 or 2 metastatic nodes, and 80.1% in patients with 3 or more metastatic nodes (P < .01). The 5-year overall survival rates of the node-positive T1b and T2 gastric cancer patients were 83.6% and 81.2%, respectively (P = .73). CONCLUSION: The prognosis of node-positive T1b gastric cancer patients after curative gastrectomy was unsatisfactory. Adjuvant chemotherapy should be considered for these patients, especially those with 3 or more metastatic nodes.

HER2 expression in locally advanced gastric cancer with extensive lymph node (bulky N2 or paraaortic) metastasis (JCOG1005-A trial).

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival. METHODS: HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results. RESULTS: Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis. CONCLUSION: The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.

The clinical significance of potentially curative resection for gastric cancer following the clearance of free cancer cells in the peritoneal cavity by induction chemotherapy.

PURPOSE: The aim of this study was to evaluate the significance of the conversion of the peritoneal cytology from positive to negative following induction chemotherapy in relation to the prognosis after subsequent resection for gastric cancer. METHODS: This retrospective study was conducted using a prospectively maintained database. A total of 47 patients with free cancer cells in the peritoneal cavity, as evaluated by staging laparoscopy, but no other evidence of distant metastasis, who underwent induction chemotherapy followed by surgery were enrolled in the study. Then, the clinicopathological factors and survival in the study subjects were assessed. RESULTS: The median survival time and 5-year overall survival rate of the 47 study participants were 20.4 months and 25.0 %, respectively. In 23 of the patients, the peritoneal cytology converted from positive to negative after the induction chemotherapy, and a microscopically margin-negative gastrectomy was performed. The median survival time of 30.4 months and the 5-year survival rate of 34.6 % of these patients was significantly more favorable than the corresponding values of 15.0 months and 17.6 % in the patients who had persistently positive cytology (P = 0.03). CONCLUSION: Based on our findings, the clearance of free cancer cells in the peritoneal cavity by induction chemotherapy improves the prognosis of patients following subsequent gastrectomy.

Clinical benefit of surgical management for gastric cancer with synchronous liver metastasis.

BACKGROUND/AIMS: The aim of this study was to evaluate the benefit of resection for liver metastasis from gastric cancer. METHODOLOGY: Consecutive 74 patients of gastric cancer who undergone the gastrectomy for primary gastric cancer and simultaneous hepatic resection for synchronous liver metastasis were enrolled. The clinicopathological factors were retrospectively compared to the prognosis. RESULTS: The median survival time and 5-year overall survival rate in 53 patients who accomplished microscopically negative margin resection was 27.4 months and 18.6%, respectively. In the multivariate survival analysis, the number of liver metastasis was identified as an independent prognostic factor (HR;2.232, 95%CI;1.036-4.808, p=0.04). When the patients undergone curative resection were subdivided into solitary and multiple liver metastasis, the median survival time and 5-year overall survival rate in a subgroup with solitary liver metastasis was 24.2 months and 27.2%, which was superior to the corresponding values of 12.6 months and 5.5% in another group with multiple liver metastasis (p=0.02). CONCLUSIONS: The resection for liver metastasis might offer a chance for long-term survival in a carefully selected group of patients. The number of liver metastasis was a reliable criterion to discriminate the subgroup of patients who are most likely to benefit from hepatic resection.

[Two cases of pancreatic cancer with multiple liver metastases treated with radical treatment after successful treatment with gemcitabine plus S-1 therapy].

UNLABELLED: We report two cases of pancreatic cancer with multiple liver metastases for which successful gemcitabine (GEM) +S-1 therapy facilitated radical resection. Case 1: A 40-year-old man with jaundice was diagnosed with pancreatic head cancer and multiple metastases. Radical treatment was not possible. Therefore, he was administered GEM +S-1 (GEM 1,000 mg/m² on days 1 and 8; S-1, 100mg/day for 14 days). Administration of seven courses of therapy achieved complete remission (CR) of the metastatic lesions. Considering the possibility of residual tumors, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Although pathological examination revealed a residual tumor in the primary lesion, R0 resection was achieved. GEM+S-1 therapy was resumed, and the patient is currently relapse-free. Case 2: A 65-year-old man with obstructive jaundice was diagnosed with pancreatic head cancer and multiple metastases. Radical treatment was not possible. Therefore, GEM +S-1 therapy was initiated. After 11 therapy courses, only one metastatic lesion remained. Radical treatment was then deemed possible, and a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination revealed residual tumors in the primary lesion and the peripancreatic lymph nodes. However, the liver nodules were only fibrotic, and their surgical radicality was R0. GEM +S-1 therapy was resumed, and the patient is currently relapse-free. CONCLUSION: The high response rate of GEM+S-1 therapy suggests its usefulness in facilitating radical resection after treatment with (GEM) +S-1.