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.

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.

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.

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.

Predictive factors for lymph node metastasis in additional gastrectomy after endoscopic resection of cT1aN0 gastric cancer.

PURPOSE: Endoscopic therapy for clinical T1aN0 (cT1aN0) gastric cancer is an excellent therapeutic strategy; however, pathological lymph node metastasis (LNM) occasionally occurs. Patients who have a potential for LNM are subject to additional gastrectomy. Our aim was to identify predictors of LNM in additional gastrectomy. METHODS: One hundred and twelve cT1aN0 gastric cancer patients undergoing additional gastrectomy after endoscopic resection were identified between 1997 and 2013. Predictors for LNM were initially selected by a univariate analysis and applied to a multivariate analysis. RESULTS: (1) Twelve patients (10.7 %) had LNM following additional gastrectomy. (2) Clinicopathological factors significantly associated with LNM were the depth of invasion (SM2 or deeper, designated as SM2) (p = 0.0018) and rigorous lymphatic invasion (ly2,3) (p < 0.001). (3) The univariate predictors for LNM were applied to the multivariate logistic regression model, and SM2 (p = 0.0027) and ly2,3 (p = 0.0028) remained significant predictors. (4) When classified into 2 × 2 subgroups, the predictability for LNM was as follows: SM2 plus ly2,3 (46.7 %), SM2 plus ly0,1 (10.0 %), M,SM1 plus ly2,3 (0 %), and M,SM1 plus ly0,1 (0 %). CONCLUSIONS: In cT1aN0 gastric cancer patients, both SM2 and ly2,3 are significant predictors for LNM that may be important as references for additional gastrectomy after endoscopic resection.

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.

Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-ß in patients with advanced gastric cancer: A randomized clinical trial.

Systemic abrogation of TGF-ß signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-ß. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-ß. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-ß was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-ß ranged from 1.85-43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-ß (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-ß remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-ß between groups A and B (P=0.019). PSK reduced the plasma TGF-ß in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-ß by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC.

A preliminary study on pre-operative tumor volumetry measured by three-dimensional computer tomography in gastric cancer.

BACKGROUND/AIMS: The aim of the present study was to evaluate the clinical significance of tumor volumetry measured by three-dimensional (3-D) multidetector row computed tomography (MD-CT). METHODOLOGY: A total of 50 patients with gastric cancer who had undergone pre-operative tumor volumetry using 3D-MD-CT followed by subsequent laparotomy (11 women, 39 men; mean age 63.9 years) were examined. Tumor volume and conventional clinicopathological factors were studied and then analyzed with respect to survival. RESULTS: Tumor volume was distributed widely and ranged from 0.16 cm3 to 363.5 cm3 with a mean of 43.6 cm3 (<10 cm3, 21 tumors; ≥10 cm3, 29 tu- mors). Significant differences in survival were found for volume (<10.0 cm3 vs. ≥10.0 cm3; p=0.0414), and depth of invasion (T1-2 vs. T3-4; p=0.0475), but not for diameter (<50 mm vs. ≥50 mm; p=0.2142), location (proximal third vs. middle or distal third; p=0.3254), macroscopic type (localized vs. invasive; p=0.3619), or microscopic type (differentiated vs. undifferentiated; p=0.1230). CONCLUSIONS: The present findings suggest that tumor volume measured by pre-operative 3D-MD-CT offers an alternative indicator for determining the prognosis in gastric cancer.

Survival outcome of Borrmann type IV gastric cancer potentially improved by multimodality treatment.

BACKGROUND: Type IV macroscopic gastric cancer has the poorest prognosis of all gastric cancer types. Although progress of multidisciplinary treatments is outstanding, the current survival outcome of such therapies is obscure. PATIENTS AND METHODS: Among 5,172 patients with gastric cancer between 1971 and 2013, 287 cases of type IV were identified (5%). We divided time period into early (1971-2004) and late periods (2005-2013), and compared their prognosis. Multivariate Cox proportional hazards model was applied to the univariate prognostic factors, and identified independent prognostic factors and long-term survivors. RESULTS: Five-year overall survival (OS) was 13% and 31% in the early and late periods, respectively (p=0.0010). Univariate prognostic factors were age, pathological tumor depth of invasion (pT), pathological lymph node metastasis (pN), peritoneal dissemination (P), intra-peritoneal cytology test (CY), and margin status. Multivariate analysis determined independent prognostic factors to be treatment period (p=0.0001), pT (p=0.0024) and P (p=0.035). Survival outcomes were stratified by combination of pT and P in both periods, where OS was improved in the late period. Long-term survivors often underwent long-term postoperative chemotherapy with S-1. CONCLUSION: Long-term postoperative S-1 chemotherapy may improve survival outcome of patients with type IV gastric cancer, and their prognosis is predicted by pT and P status.

Benefit of neoadjuvant chemotherapy for Siewert type II esophagogastric junction adenocarcinoma.

AIM: Our objective was to clarify if preoperative chemotherapy was associated with improved survival in Japanese patients with Siewert type II adenocarcinoma of the esophagogastric junction. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 86 patients with Siewert type II adenocarcinoma who underwent R0 resection at the Kitasato University between 1997 and 2013. Cox regression analysis using a backward stepwise selection method was performed to identify independent prognostic factors for relapse-free survival (RFS). RESULTS: The median age was 67 years. The male:female ratio was 74:12. Right thoracic, left thoracic and transhiatal approaches were performed in 10, 10 and 66 patients, respectively, and perioperative transfusion in 16 patients. Preoperative chemotherapy was administered to 19 patients; out of these, 13 received chemotherapy using the DCS regimen (docetaxel 40 mg/m(2), day 1; cisplatin 60 mg/m(2), day 1; S-1 80-120 mg/body, days 1-14; every 28 days). A median of three cycles of preoperative DCS chemotherapy were used. Histological responses of 1b, 2, 3 and unknown grades were obtained in three, three, four and three patients, respectively. The 5-year RFS rate was 55%, and the median follow-up period was 36 months. Cox regression analysis regarding RFS identified (y)pN1-3 [hazard ratio (HR)=4.44; 95% confidence interval (CI)=1.98-11.27], performance of perioperative transfusion (HR=4.71; 95% CI=1.69-11.88) and no preoperative chemotherapy (HR=3.75; 95% CI=1.22-14.26) as significant and independent indicators of poor prognosis. CONCLUSION: Preoperative chemotherapy using DCS is potentially beneficial for Japanese patients with Siewert type II adenocarcinoma. Further prospective clinical studies are required to confirm our findings.

Impact of lower mediastinal lymphadenectomy for the treatment of esophagogastric junction carcinoma.

AIM: To define the optimal extent of resection for esophagogastric junction (EGJ) carcinoma. PATIENTS AND METHODS: We retrospectively reviewed medical records of 193 patients with EGJ adenocarcinoma or squamous cell carcinoma who underwent surgery at the Kitasato University. An index was calculated to evaluate the therapeutic value of lymphadenectomy. RESULTS: The following factors were identified as independent predictors of poor survival: (y)pT3-4, (y)pN3, ly2-3, no performance of splenectomy and R1-2. Although metastases were found in mediastinal lymph-nodes in patients with esophageal invasion of ≤30 mm, the index was 0 for all mediastinal lymph-nodes. By contrast, in patients with esophageal invasion of >30 mm, the index was 13.9 for the No. 110 nodes, which was the second highest after the index for the No. 1 nodes. CONCLUSION: In EGJ cancer patients with esophageal invasion of >30 mm, aggressive lower mediastinal lymphadenectomy with R0 resection is required to obtain the best result.

Preoperative tumor size is a critical prognostic factor for patients with Borrmann type III gastric cancer.

PURPOSE: This study was designed to clarify whether preoperative tumor size is an independent prognostic factor (IPF) for patients with Borrmann type III gastric cancer. METHODS: The study group comprised 350 patients with Borrmann type III gastric cancer. We performed a log-rank plot analysis to establish the threshold value of preoperative tumor size for the prediction of overall survival (OS). Factors with P < 0.10 on univariate prognostic analyses for OS were put into a Cox's proportional hazards model to identify the IPFs. RESULTS: Peritoneal lavage cytology (CY) was the strongest IPF for patients with Borrmann type III gastric cancer (P < 0.0001). We were able to measure the tumor size preoperatively in 135 patients with negative CY results (CY0). The cutoff tumor size for the prediction of OS was 5.3 cm. A Cox's proportional hazards model showed that pathological lymph-node metastasis (P = 0.007) and preoperative tumor size (P = 0.018) were significant IPFs in the CY0 patients. Patients with a preoperative tumor size of <5.3 cm had satisfactory outcomes, with a 5-year OS rate of >80 %. CONCLUSIONS: Preoperative tumor size is an IPF for patients with Borrmann type III gastric cancer and CY0. Thus, preoperative tumor size may be a useful factor for deciding on whether neoadjuvant chemotherapy is indicated.

Prognostic impact of venous invasion in stage IB node-negative gastric cancer.

BACKGROUND: Little is known about risk factors for recurrence in stage IB gastric cancer without lymph node metastasis. The aims of this study were to determine prognostic factors associated with long-term survival and to clarify patterns of recurrence. METHODS: We retrospectively reviewed the medical records of 130 patients with primary gastric cancer who underwent gastrectomy at Kitasato University East Hospital from 2001 through 2010 and analyzed clinicopathological characteristics associated with survival and patterns of recurrence. RESULTS: Of the 130 patients, 12 (9.2%) had recurrence, among whom 10 (83%) patients died. Four patients (3.1%) died of other diseases. The 5-year overall survival rate was 89%. Of the 12 patients with recurrence, 7 (58%) had liver metastasis, 3 (25%) had distant lymph-node metastasis, 2 (17%) had peritoneal dissemination, and 1 (8.3%) had locoregional recurrence. Patients with tumors more than 5 cm in diameter tended to have recurrence within 1 year. Patients who had recurrence more than 2 years after surgery tended to survive for longer than 5 years after recurrence. Moderate or marked venous invasion (v2 or v3) and age >65 years were significantly associated with relapse-free and overall survival on univariate analysis. On multivariate analysis, the only independent prognostic factor for relapse-free and overall survival was venous invasion. CONCLUSIONS: Moderate or marked venous invasion (v2 or v3) is an independent predictor of relapse-free and overall survival in stage IB node-negative gastric cancer. Postoperative adjuvant chemotherapy, currently not given to this subgroup of patients, may improve the outcomes of patients with stage IB node-negative gastric cancer, particularly when accompanied by venous invasion.

Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer.

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S-1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S-1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF-1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5-year Relapse Free Survival (5y-RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF-1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF-1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11-2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3-positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.

Simple prognostic indicators using macroscopic features and age in advanced gastric cancer.

BACKGROUND/AIM: Macroscopic features and age may be important prognostic factors that discriminate survival among clinical conditions requiring different therapeutic strategies of advanced gastric cancer (AGC), and this study aimed to identify their clinical relevance. METHODOLOGY: A total of 232 AGC patients who had Surgical T2b or beyond was enrolled to identify clinical indicators, including macroscopic features in combination with age. RESULTS: Macroscopic features were divided into 3 categories (types I/II/V, III, and IV), which included stage IV in 24%, 53%, and 72% (P < 0.0001), respectively. Macroscopic features (P < 0.0001), histological features (P = 0.025), and pathological infiltration type (P = 0.0003) were all univariate prognostic factors, as well as stage (P < 0.0001) and age (P = 0.009). However, the multivariate proportional hazards model found that macroscopic features (P = 0.0013) and age (P = 0.0091) were the only factors independent of stage (P <0.0001). Both factors clearly classified the patients into 4 groups (young type 1/II/V (group 1), elderly type I/II/V (group 2), type III and young type IV (group 3), and elderly type IV (group 4) with different prognoses. CONCLUSIONS: Macroscopic features and age were simple indicators of prognosis in AGC. Both factors may have great potential to develop prognostic categories that effectively classify AGC into categories requiring different therapeutic strategies.

Preoperative dual-phase 3D CT angiography assessment of the right hepatic artery before gastrectomy.

PURPOSES: In the current study, we evaluated the efficacy of dual-phase three-dimensional (3D) CT angiography (CTA) in the assessment of the vascular anatomy, especially the right hepatic artery (RHA), before gastrectomy. METHODS: The study initially included 714 consecutive patients being treated for gastric cancer. A dual-phase contrast-enhanced CT scan using 32-multi detector-row CT was performed for all patients. RESULTS: Among the 714 patients, 3D CTA clearly identified anomalies with the RHA arising from the superior mesenteric artery (SMA) in 49 cases (6.9 %). In Michels' classification type IX, the common hepatic artery (CHA) originates only from the SMA. Such cases exhibit defective anatomy for the CHA in conjunction with the celiac-splenic artery system, resulting in direct exposure of the portal vein beneath the #8a lymph node station, which was retrospectively confirmed by video in laparoscopic gastrectomy cases. Fused images of both 3D angiography and venography were obtained, and could have predicted the risk preoperatively, and the surgical finding confirmed its usefulness. CONCLUSION: Preoperative evaluations using 3D CTA can provide more accurate information about the vessel anatomy. The fused images from 3D CTA have the potential to reduce the intraoperative risks for injuries to critical vessel, such as the portal vein, during gastrectomy.

Lymph node ratio is a critical prognostic predictor in gastric cancer treated with S-1 chemotherapy.

BACKGROUND: S-1 is an oral anticancer drug widely used in postoperative adjuvant therapy for patients in Japan with stage II/III gastric cancer. Candidates for more intense adjuvant treatments need to be identified, particularly among patients with stage III cancer. METHODS: Univariate and multivariate analyses were conducted for patients with stage II/III gastric cancer who underwent surgery and received S-1 postoperatively between 2000 and 2010. RESULTS: Factors indicating poor prognosis identified by univariate analysis include male sex (P = 0.022), age ≥67 years (P = 0.021), intestinal-type histology (P = 0.049), lymph node ratio ≥16.7 % (P < 0.0001), open surgery (P = 0.039), as well as the 13th JGCA stage (P < 0.0001) and the 14th JGCA/7th International Union Against Cancer (UICC) stage (P < 0.0001). Multivariate analysis revealed that lymph node ratio ≥16.7 % and intestinal-type histology were significant as predictors of prognosis, independent from the pathological stages. Based on these and other findings, stage IIIC cancer on the 14th JGCA/7th UICC stage system in combination with the lymph node ratio could identify patients with extremely high risk for recurrence CONCLUSIONS: Our current findings suggest that lymph node ratio ≥16.7 % in combination with the new staging system could be a useful prognostic indicator in advanced gastric cancer. Because these high-risk patients cannot be identified preoperatively by any diagnostic tool, further improvement in postoperative adjuvant therapy is warranted.

Comparison of the Heller-Toupet procedure with the Heller-Dor procedure in patients who underwent laparoscopic surgery for achalasia.

PURPOSE: We compared the outcomes of Toupet fundoplication with those of Dor fundoplication in patients with achalasia who underwent laparoscopic Heller myotomy. METHODS: Seventy-two patients with achalasia and dysphagia underwent laparoscopic Heller myotomy with fundoplication performed by a single surgeon. Heller-Toupet fundoplication (HT) was performed in 30 patients, and Heller-Dor fundoplication (HD) was done in 42. The symptoms and esophageal function were retrospectively assessed in both groups. RESULTS: The dysphagia scores significantly decreased after both the HT and HD procedures, and did not differ significantly between them. The incidence of reflux symptoms was significantly higher after HT (26.7%) than after HD (7.1%). The lower esophageal sphincter (LES) resting pressure significantly decreased after both HT and HD. Upon endoscopic examination, the incidence of reflux esophagitis was significantly higher after HT (38.5%) than after HD (8.8%). During esophageal pH monitoring, the fraction time at pH <4 was similar in the patients who underwent HT and HD. CONCLUSIONS: Laparoscopic Heller myotomy provided significant improvements in the dysphagia symptoms of achalasia patients, regardless of the type of fundoplication. The incidences of reflux symptoms and reflux esophagitis were higher after HT than after HD. However, the results of pH monitoring did not differ between the procedures.