Robust vascular invasion concurrent with intense EGFR immunostaining can predict recurrence in patients with stage IB node-negative gastric cancer.

PURPOSE: The prognosis of most patients with stage IB node-negative gastric cancer is good without postoperative chemotherapy; however, about 10% suffer recurrence and inevitably die. We conducted this study to establish the optimal indications for postoperative adjuvant chemotherapy in patients at risk of recurrence. METHODS: The subjects of this retrospective study were 124 patients with stage IB node-negative gastric cancer, who underwent gastrectomy at the Kitasato University East Hospital, between 2001 and 2010. We reviewed EGFR immunohistochemistry (IHC) as well as clinicopathological factors. RESULTS: Of the 124 patients, 47 (38%) showed intense EGFR IHC (2+ or 3+), with significantly less frequency than in stage II/III advanced gastric cancer (p < 0.001). According to univariate analysis, intense EGFR IHC was significantly associated with relapse-free survival (RFS) (p = 0.023) and associated with overall survival (OS) (p = 0.045) as well as vascular invasion (p = 0.031). On the multivariate Cox proportional hazards model, intense EGFR IHC(p = 0.016) was an independent prognostic predictor for RFS, and both vascular invasion (p = 0.033) and intense EGFR IHC (p = 0.031) were independent prognostic predictors for OS. The combination of both factors increased the risk of recurrence (p = 0.001). CONCLUSIONS: In stage IB node-negative gastric cancer, vascular invasion and intense EGFR IHC increase the likelihood of recurrence. We recommend adjuvant chemotherapy for such patients because of the high risk of metachronous recurrence.

Comprehensive Diagnosis of Bacterial Infection Associated with Acute Cholecystitis Using Metagenomic Approach.

Acute cholecystitis (AC), which is strongly associated with retrograde bacterial infection, is an inflammatory disease that can be fatal if inappropriately treated. Currently, bacterial culture testing, which is basically recommended to detect the etiological agent, is a time-consuming (4-6 days), non-comprehensive approach. To rapidly detect a potential pathogen and predict its antimicrobial susceptibility, we undertook a metagenomic approach to characterize the bacterial infection associated with AC. Six patients (P1-P6) who underwent cholecystectomy for AC were enrolled in this study. Metagenome analysis demonstrated possible single or multiple bacterial infections in four patients (P1, P2, P3, and P4) with 24-h experimental procedures; in addition, the CTX-M extended-spectrum ß-lactamase (ESBL) gene was identified in two bile samples (P1 and P4). Further whole genome sequencing of Escherichia coli isolates suggested that CTX-M-27-producing ST131 and CTX-M-14-producing novel-ST were identified in P1 and P4, respectively. Metagenome analysis of feces and saliva also suggested some imbalance in the microbiota for more comprehensive assessment of patients with AC. In conclusion, metagenome analysis was useful for rapid bacterial diagnostics, including assessing potential antimicrobial susceptibility, in patients with AC.

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer.

PURPOSE: A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy. METHODS: The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review. RESULT: Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018). CONCLUSION: Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy.

AIM: To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS: One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS: Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION: A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer.

DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer.

BACKGROUND: Minimal residual disease of the peritoneum is challenging for early cancer detection in gastric cancer (GC). Utility of PCR amplification of cancer-derived DNA has been considered feasible due to its molecular stability, however such markers have never been available in GC clinics. We recently discovered cancer-specific methylation of CDO1 gene in GC, and investigated the clinical potential to detect the minimal residual disease. METHODS: One hundred and two GC patients were investigated for peritoneal fluid cytology test (CY), and detection level of the promoter DNA methylation of CDO1 gene was assessed by quantitative methylation specific PCR (Q-MSP) in the sediments (DNA CY). RESULTS: (1) CY1 was pathologically confirmed in 8 cases, while DNA CY1 was detected in 18 cases. All 8 CY1 were DNA CY1. (2) DNA CY1 was recognized in 14.3, 25.0, 20.0, and 42.9%, in macroscopic Type II, small type III, large type III, and type IV, respectively, while it was not recognized in Type 0/I/V. (3) DNA CY1 was prognostic relevance in gastric cancer (p = 0.0004), and its significance was robust among Type III/IV gastric cancer (p = 0.006 for overall survival and p = 0.0006 for peritoneal recurrence free survival). (4) The peritoneal recurrence was hardly seen in GC patients with potent perioperative chemotherapy among those with DNA CY1. CONCLUSIONS: DNA CY1 detected by Q-MSP for CDO1 gene promoter DNA methylation has a great potential to detect minimal residual disease of the peritoneum in GC clinics as a novel DNA marker.

Evaluating the timing of laparoscopic cholecystectomy for acute cholecystitis in an experienced center based on propensity score matching.

INTRODUCTION: This study evaluates the therapeutic outcomes for laparoscopic cholecystectomy for acute cholecystitis based on the time from symptom onset to surgery. METHODS: This study enrolled 224 patients. Patients' characteristics and operative outcomes were compared between patient groups based on the timing of laparoscopic cholecystectomy from symptom onset: ≤72 h versus >72 h, and ≤7 days versus ≥8 days. Then, we performed propensity score matching of 13 relevant variables, including patient demographics, examination findings, and therapeutic factors. RESULTS: The early surgery groups (≤72 h and ≤7 days) had significantly younger patients with fewer comorbidities and a shorter duration from symptom onset to presentation before performed propensity score matching. These groups also had shorter surgery, postoperative hospital stay, and total length of stay. Other operative outcomes, including blood loss, conversion to open surgery, bile duct injury, and postoperative complications, did not significantly differ among the groups. After propensity score matching, all therapeutic outcomes, including duration of surgery, showed no significant differences in either analysis. CONCLUSIONS: In a center with sufficient experience, performing laparoscopic cholecystectomy at the earliest possible time after presentation was a safe therapeutic strategy for each patient with acute cholecystitis, regardless of the time from symptom onset.

Prognostic Advantage of Docetaxel/Cisplatin/ 5-Fluorouracil Neoadjuvant Chemotherapy in Clinical Stage II/III Esophageal Squamous Cell Carcinoma due to Excellent Control of Preoperative Disease and Postoperative Lymph Node Recurrence.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become prevalent in esophageal squamous cell carcinoma (ESCC), but its long-term prognostic advantages remain unclear. The latest prognostic outcomes in clinical Stage (cStage) II/III ESCC with NAC were herein elucidated. PATIENTS AND METHODS: NAC prior to curative treatment was done in 115 cStage II/III ESCC patients with either cisplatin (CDDP)/5-fluorouracil (5-FU; CF) (n = 41) or docetaxel/CDDP/5-FU (DCF) NAC (n = 74) between 2007 and 2013. RESULTS: (1) Esophagectomy was finally performed in 35 of the 41 CF NAC cases and in 48 of the 74 DCF NAC cases. The preservation rate of the esophagus was higher in the DCF NAC than in the CF NAC (p = 0.018). (2) The overall survival was better in DCF NAC than in CF NAC (p = 0.071), and progression-free survivals were 58.3% with DCF and 30.5% with CF (p = 0.0060). DCF NAC was associated with fewer cases of progression than CF NAC (p = 0.0040), largely due to excellent control of the preoperative disease (p = 0.018) and postoperative lymph node recurrence (p = 0.014). CONCLUSION: DCF NAC in cStage II/III ESCC could have a great potential to achieve a better prognosis due to suppression of specific progression events with a higher preservation rate of the esophagus.

Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma.

We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed. (i) The median TaqMeth value of CDO1 methylation was 9.4, ranging from 0 to 279.5. CDO1 methylation was significantly different between cStage I and cStage II/III (P = 0.02). (ii) On the log-rank plot, the optimal cut-off value was determined to be 8.9; ESCC patients with high CDO1 methylation showed a significantly worse prognosis than those with low CDO1 methylation (P = 0.02). (iii) A multivariate Cox proportional hazards model identified only CDO1 hypermethylation as an independent prognostic factor (HR 2.00, CI 1.09-3.78, P = 0.03). (iv) CDO1 hypermethylation stratified ESCC patients' prognosis in cStage II/III for both neoadjuvant chemo(radio)therapy (NAC)-positive and NAC-negative cases. Moreover, the CDO1 methylation level was significantly lower in cases with Grade 2/3 than in those with Grade 0/1 (P = 0.02) among cStage II/III ESCC patients with NAC. Promoter DNA hypermethylation of CDO1 could be an independent prognostic factor in ESCC; it may also reflect NAC eradication of tumor cells in the primary tumors.

Postoperative quality of life after laparoscopy-assisted pylorus-preserving gastrectomy compared With laparoscopy-assisted distal gastrectomy: A cross-sectional postal questionnaire survey.

BACKGROUND: Little is known about postgastrectomy syndrome and quality of life (QOL after laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). The aim of this study was to assess postgastrectomy syndrome and QOL after LAPPG as compared with laparoscopy-assisted distal gastrectomy with Billroth-I reconstruction (LADGBI). METHODS: Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaires were sent by mail to 167 patients. To balance the characteristics of the groups, propensity score matching was performed. RESULTS: Of the 167 patients sent questionnaires, 112 (67%) responded, including 47 who underwent LAPPG and 65 who underwent LADGBI. After propensity score matching, the LAPPG group scored significantly better on the diarrhea and dumping subscales. Multiple regression analysis showed that female sex and LADGBI were independent factors predicting dumping. Evaluation of outcome measures for singular symptom showed that the LAPPG group scored significantly worse on the acid regurgitation subscale, but significantly better on the lower abdominal pain and early dumping abdominal subscales. CONCLUSION: LAPPG is superior to LADGBI for ameliorating postgastrectomy syndrome and maintaining QOL. LAPPG is recommended for patients with cT1N0 middle third gastric cancer.

Neutrophil/lymphocyte ratio has a prognostic value for patients with terminal cancer.

BACKGROUND: Determining prognosis in advanced cancer is of key importance. Various prognostic scores have been developed. However, they are often very complex. In this study, we evaluated the feasibility of neutrophil/lymphocyte ratio (NLR) as an index to estimate survival in terminal cancer patients. METHODS: NLR was calculated retrospectively based on blood tests performed at 3 months, 2 months, 4 weeks, 3 weeks, 2 weeks, 1 week, and within 3 days before death in 160 cancer patients (82 men, 78 women; age range, 33-99 years; mean age, 69.8 years). RESULTS: NLR increased significantly with time (P < 0.0001). Mean NLR was significantly higher in patients who died within 4 weeks (29.82) than in those who lived more than 4 weeks (6.15). The NLR cutoff point was set at 9.21 according to receiver operating characteristic curve analysis (area under the curve, 0.82; 95% confidence interval, 0.79-0.85). We inferred that life expectancy would be <4 weeks when NLR >9.21. The sensitivity, specificity, positive predictive value, and negative predictive value were 65.6, 84.1, 90.6, and 51.1%, respectively. The positive and negative likelihood ratios were 4.125 and 0.409, respectively. CONCLUSIONS: NLR appears to be a useful and simple parameter to predict the clinical outcomes of patients with terminal cancer.

Delayed perforation after endoscopic submucosal dissection for early gastric cancer: Clinical features and treatment.

Perforation is an important procedural complication of endoscopic submucosal dissection (ESD) for early gastric cancer. Although the incidence of delayed perforation after ESD is low, extreme caution is necessary because many cases require surgical intervention. Among 1984 lesions of early gastric cancer treated in our hospital by ESD in 1588 patients from September 2002 through March 2015, delayed perforation developed in 4 patients (4 lesions, 0.25%). A diagnosis of delayed perforation requires prompt action, including surgical intervention when required.

Long-term prognostic outcome of cT1 gastric cancer patients who underwent laparoscopic gastrectomy after 5-year follow-up.

PURPOSE: We have reported that short-term and middle-term clinical outcomes including prognosis after laparoscopy-assisted gastrectomy (LAG) are excellent in cT1 gastric cancer. METHODS: In this study, long-term prognosis was finally confirmed in detail in 491 cT1 gastric cancer patients who underwent LAG between 1998 and 2010, where clinical course was completely pursued for recurrent cases. RESULTS: Among the 491 cases, follow-up examination at 5 years (60 months) after operation was done in 423 (86.2 %). Recurrent cases were seen in nine cases (1.8 %) who inevitably died despite aggressive multimodality treatments. The initial recurrent sites were the peritoneum in three, the liver in two, the bone in one, the ovary in one, the liver/bone in one, and the Virchow lymph node/bone in one. As a result, the 5-year disease-specific survival (DSS) was 98.3 %. cT1 gastric cancer was finally diagnosed as pathological stages IA to III, and the 5-year DSS was 99.7 % in pathological stage IA, 96.9 % in pathological stage IB, and 81 % in pathological stage II/III. The initial recurrent sites were the liver/bone in stage IA (M/N0), the liver in stage IB (MP/N0), the liver in stage IIA (MP/N1), the liver and the ovary in two stages IIB (T1N3), 3 peritoneum and 1 Virchow lymph node/bone in four stage III cases. Importantly, there were no initial recurrences in the regional lymph node, and all recurrences were seen within 5 years after operation. CONCLUSIONS: Although long-term prognostic outcome was extremely good in cT1 gastric cancer patients who underwent LAG, cases with recurrence inevitably died due to disease progression.

Neoadjuvant chemotherapy of triplet regimens of docetaxel/cisplatin/5-FU (DCF NAC) may improve patient prognosis of cStage II/III esophageal squamous cell carcinoma-propensity score analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) with CF (cisplatin/5-FU) was demonstrated to improve survival of clinical stage II/III (cStage II/III) esophageal squamous cell carcinoma (ESCC), however prognostic outcome remains unsatisfactory. We have recently reported preliminary potentiality of short-term survival benefit by NAC with DCF (docetaxel/cisplatin/5-FU). PATIENTS AND METHODS: Thirty-eight ESCC patients who underwent DCF NAC between 2009 and 2012 were investigated for prognosis with a median follow-up period of 49 months as compared to those with CF NAC. RESULTS: (1) ESCC patients with DCF NAC showed 66% of 3-year progression-free survival (PFS), which is significantly superior to that of CF NAC (38%) (p = 0.018). ESCC patients with DCF NAC showed 79% of 3-year overall survival (OS), which is marginally significantly superior to that of CF NAC (65%) (p = 0.093). (2) The multivariate Cox proportional hazards model revealed that DCF NAC was an independent prognostic factor for PFS (p = 0.0013) and OS (p = 0.047), respectively, when adjusted for patient sex, age, cT, cN, and preoperative borderline resectability. (3) Patients with more advanced stage were rather frequently included in DCF NAC than in CF NAC, however there was no significant difference. Nevertheless, propensity score (PS) to predict DCF NAC was significantly higher than CF NAC (p = 0.019). (4) Both NAC and PS were again applied to the multivariate Cox proportional hazards model, and DCF NAC was the only remnant prognostic indicator for PFS (p = 0.0044) and OS (p = 0.063). CONCLUSION: Prognosis may be significantly improved in cStage II/III ESCC patients who underwent DCF NAC than those with CF NAC.

Chemoradiotherapy for patients with recurrent lymph-node metastasis or local recurrence of gastric cancer after curative gastrectomy.

OBJECTIVES: Whether chemoradiotherapy (CRT) is clinically beneficial for the management of postoperative recurrence of advanced gastric cancer remains unclear. We retrospectively studied treatment outcomes in patients who had unresectable localized recurrence after surgery for advanced gastric cancer and evaluated the safety and efficacy of CRT. METHODS: The study group comprised 21 patients who received concurrent CRT for unresectable localized recurrence after undergoing R0 resection for stage II/III advanced gastric cancer. Localized recurrence was defined as a few or limited recurrent lesions. RESULTS: The recurrence pattern was anastomotic recurrence in 7 patients, abdominal lymph-node recurrence in 12, and anastomotic recurrence plus abdominal lymph-node recurrence in 2. The median total dose of radiotherapy was 48.6 Gy (range 39.6-56.0), and the CRT completion rate was 100 % (21 of 21 patients). CRT-related grade 3 or higher toxicity comprised neutropenia in 33.3 % of patients and anorexia in 9.5 %. The response rate was 61.9 % (complete response 38.1 %, partial response 23.8 %). The median overall survival was 35.0 months. CONCLUSIONS: We conclude that CRT may become one treatment strategy for the management of unresectable localized recurrence after curative resection of advanced gastric cancer.

Potential benefits of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy for cT1 upper-third gastric cancer.

BACKGROUND: Few reports have compared laparoscopy-assisted proximal gastrectomy (LAPG) with laparoscopy-assisted total gastrectomy (LATG) in patients with cT1N0 gastric cancer. This study assessed the safety and feasibility of LAPG with esophagogastrostomy in these patients and compared postgastrectomy disturbances and nutritional status following LAPG and LATG. METHODS: This study compared 40 patients who underwent LAPG with esophagogastrostomy and 59 who underwent LATG with esophagojejunostomy, both with OrVil™. Surgical outcomes, postoperative complications, nutritional status at 1 and 2 years, and relapse-free survival were compared in these two groups. RESULTS: Operation time was significantly shorter in the LAPG group than in the LATG group (280 min vs. 365 min, P < 0.001). Although the rate of surgical complications was similar in the two groups, the rate of anastomotic stricture was significantly higher in the LAPG group than in the LATG group (28 vs. 8.4 %; P = 0.012). Rates of reflux esophagitis graded A or higher in the Los Angeles classification were 10 and 5.1 %, respectively. Hemoglobin levels 2 years after surgery, relative to baseline levels, were significantly higher in the LAPG group than in the LATG group (98.6 vs. 92.9 %, P = 0.020). Body weight, albumin and total protein concentrations, and total lymphocyte count 1 and 2 years after surgery were slightly, but not significantly, higher in the LAPG group. Relapse-free survival rates were similar, as were 5-year overall survival rates (86 vs. 79 %, P = 0.42). CONCLUSIONS: LAPG with esophagogastrostomy using OrVil™ was safe and feasible for patients with cT1N0 gastric cancer. LAPG may have nutritional advantages over LATG, but the rate of anastomotic stricture was significantly higher for LAPG than for LATG.

Lectin microarray technology identifies specific lectins related to lymph node metastasis of advanced gastric cancer.

BACKGROUND: Although various molecular profiling technologies have the potential to predict specific tumor phenotypes, the comprehensive profiling of lectin-bound glycans in human cancer tissues has not yet been achieved. METHODS: We examined 242 advanced gastric cancer (AGC) patients without or with lymph node metastasis-N0 (n = 62) or N+ (n = 180)-by lectin microarray, and identified the specific lectins highly associated with AGC phenotypes. RESULTS: In seven gastric cancer cell lines, in contrast to expressed-in-cancer lectins, not-expressed-in-cancer (NEC) lectins were tentatively designated by lectin microarray. Binding signals of the specific lectins were robustly reduced in AGC patients with N+ status as compared with those with N0 status. The receiver operating characteristic curve determined the optimal cutoff value to differentiate N0 status from N+ status, and subsequent profiling of NEC lectins identified Vicia villosa agglutinin (VVA) association with the significant other lectins involved in lymph node metastasis. VVA reaction was clearly found on cancer cells, suggesting that it may result from carcinoma-stroma interaction in primary AGC, because VVA is an NEC lectin. Most intriguingly, VVA reaction was remarkably attenuated in the tumor cells of the metastatic lymph nodes, even if it was recognized in primary AGC. In AGC, histological type was strongly associated with soybean agglutinin and Bauhinia purpurea lectin, whereas p53 mutation was the best correlated with Griffonia simplicifolia lectin II. CONCLUSIONS: Lectin microarrays can be used to very accurately quantify the reaction of glycans with tumor tissues, and such profiles may represent the specific phenotypes, including N+ status, histological type, or p53 mutation of AGC.

Laparoscopic versus open distal gastrectomy for early gastric cancer in Japan: long-term clinical outcomes of a randomized clinical trial.

PURPOSE: We report the long-term clinical outcomes of a randomized clinical trial comparing laparoscopy-assisted distal gastrectomy (LADG) with open DG (ODG). METHODS: Between 2005 and 2008, 63 patients with clinical T1 (cT1) gastric cancer were randomly assigned to undergo either LADG or ODG. Long-term clinical outcomes included prospective questionnaire-based symptoms and survival. RESULTS: Based on the responses to the prospective questionnaires, patients who underwent LADG reported greater satisfaction and were more likely to favor the procedure than those who underwent ODG. The most notable difference in symptoms was related to wound pain and diarrhea. After ODG, wound pain reduced in intensity but persisted throughout the follow-up. Surprisingly, diarrhea was more frequent after LADG than after ODG, possibly due to overeating, because symptoms elicited by overeating, such as vomiting after a meal or heartburn, were also more frequent after LADG. In terms of long-term survival, there were no cases of recurrence in either group. CONCLUSIONS: LADG was associated with less wound pain during long-term follow-up after surgery, whereas symptoms related to overeating were common. Based on our findings and the patients' reported satisfaction, we recommend LADG for cT1 gastric cancer as an effective procedure with excellent long-term survival.

A Risk Model for Surgical Site Infection in the Gastric Cancer Surgery Using Data of 790 Patients.

BACKGROUND: Understanding risk factors of surgical site infections (SSIs) in gastrectomy is important to provide the best treatment for the patients with gastric cancer. METHODS: This is a retrospective observational study using the medical records of 790 patients with gastrectomy from 2005 through 2009. SSIs were classified into incisional SSIs (iSSIs) and organ/space SSIs (o/sSSIs). RESULTS: iSSIs and o/sSSIs were detected in 41 (5.2%) patients and 68 (8.6%) patients, respectively. Open surgery was the only independent risk factor (p = 0.028) for iSSIs, while open surgery (p = 0.004), concurrent splenectomy (p < 0.001), operative time ≥220 min (p = 0.009), preoperative body mass index ≥20.8 kg/m2 (p = 0.004) and male gender (p = 0.028) were the independent risk factors for o/sSSIs. We created a risk model for o/sSSIs using these independent risk factors. The C-index model discrimination was 0.84 (p < 0.001), and the calibration of the models demonstrated a linear correlation between the predicted and observed probability. CONCLUSION: We reported the risk factors of SSIs for gastrectomy. The risk model developed in this study for o/sSSIs pertaining to gastric cancer surgery would contribute to provide guidance for the development of best practices.

Exclusive Association of p53 Mutation with Super-High Methylation of Tumor Suppressor Genes in the p53 Pathway in a Unique Gastric Cancer Phenotype.

BACKGROUND: A comprehensive search for DNA methylated genes identified candidate tumor suppressor genes that have been proven to be involved in the apoptotic process of the p53 pathway. In this study, we investigated p53 mutation in relation to such epigenetic alteration in primary gastric cancer. METHODS: The methylation profiles of the 3 genes: PGP9.5, NMDAR2B, and CCNA1, which are involved in the p53 tumor suppressor pathway in combination with p53 mutation were examined in 163 primary gastric cancers. The effect of epigenetic reversion in combination with chemotherapeutic drugs on apoptosis was also assessed according to the tumor p53 mutation status. RESULTS: p53 gene mutations were found in 44 primary gastric tumors (27%), and super-high methylation of any of the 3 genes was only found in cases with wild type p53. Higher p53 pathway aberration was found in cases with male gender (p = 0.003), intestinal type (p = 0.005), and non-infiltrating type (p = 0.001). The p53 pathway aberration group exhibited less recurrence in lymph nodes, distant organs, and peritoneum than the p53 non-aberration group. In the NUGC4 gastric cancer cell line (p53 wild type), epigenetic treatment augmented apoptosis by chemotherapeutic drugs, partially through p53 transcription activity. On the other hand, in the KATO III cancer cell line (p53 mutant), epigenetic treatment alone induced robust apoptosis, with no trans-activation of p53. CONCLUSION: In gastric cancer, p53 relevant and non-relevant pathways exist, and tumors with either pathway type exhibited unique clinical features. Epigenetic treatments can induce apoptosis partially through p53 activation, however their apoptotic effects may be explained largely by mechanism other than through p53 pathways.

A Multi-institutional, Prospective, Phase II Feasibility Study of Laparoscopy-Assisted Distal Gastrectomy with D2 Lymph Node Dissection for Locally Advanced Gastric Cancer (JLSSG0901).

BACKGROUND: The efficacy and safety outcomes of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection for locally advanced gastric cancer remain unclear. Therefore, we conducted a randomized, controlled phase II trial to confirm the feasibility of LADG in terms of technical safety, and short-term surgical outcomes were investigated. METHODS: Eligibility criteria included pre-operatively diagnosed advanced gastric cancer that could be treated by distal gastrectomy with D2 lymph node dissection; MP, SS, and SE without involvement of other organs; and N0-2 and M0. Patients aged 20-80 years were pre-operatively randomized. RESULTS: In total, 180 patients were registered and randomized to the open (89 patients) and laparoscopic arms (91 patients). Among 91 patients in the laparoscopic arm, 86 underwent laparoscopic gastrectomy according to the study protocol. Regarding the primary endpoint of the phase II trial, the proportion of patients with either anastomotic leakage or pancreatic fistula was 4.7 % (4/86). The grade 3 or higher morbidity rate, including systemic and local complications, was 5.8 %. Conversion to open surgery was required for 1 patient (1.2 %), without any intra-operative complication. The post-operative mortality rate was 0, and no patient required readmission for surgical complications within 6 months after initial discharge. CONCLUSIONS: The technical safety of LADG with D2 lymph node dissection for locally advanced gastric cancer was demonstrated. A phase III trial to confirm the non-inferiority of this procedure to open gastrectomy in terms of long-term outcomes is ongoing. Registered Number: UMIN 000003420 ( www.umin.ac.jp/ctr/).