Lymph Node Progression and Optimized Node Dissection of Middle Thoracic Esophageal Squamous Cell Carcinoma in the Latest Therapeutic Surgical Strategy.

PURPOSE: The aim of this study is to elucidate the optimized lymph node dissection range in middle thoracic (Mt) esophageal squamous cell carcinoma (ESCC) requiring surgery. PATIENTS AND METHODS: We retrospectively analyzed 165 ESCC patients who underwent surgery with curative intent between 2009 and 2016, including 99 (60%) with MtESCC. Preoperative chemotherapy was administered in more than 80% of cStage II/III MtESCC patients. The rates of pathological and potential metastasis (representing recurrences) to lymph nodes and prognosis (median follow-up 52 months) were clarified. Lymph node dissection efficacy was assessed by calculating the efficacy index (EI) for each lymph node. RESULTS: No. 2R had the highest rate of metastasis, with frequencies of 13/38/46% in cStage I/II/III, respectively, with the highest EI in MtESCC. Recurrences were seen in about 2-10% in the regional (nos. 1, 2L, 4R, and 10) and extraregional lymph nodes (paraaortic lymph node). The EI of lymph nodes was found to exhibit the highest score of 15 for no. 2R, followed by 11.5 for no. 17. The 5-year overall survival (OS) in MtESCC patients who underwent no. 2R lymph node dissection was 73.8%, while those who did not undergo no. 2R dissection did never reach 5-year OS (P = 0.002). CONCLUSIONS: Meticulous lymph node dissection of no. 2R is the most important for long-term survival, and mandatory with the highest priority in MtESCC.

Comprehensive Exploration to Identify Predictive DNA Markers of ΔNp63/SOX2 in Drug Resistance in Human Esophageal Squamous Cell Carcinoma.

BACKGROUND: OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer. METHODS: OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC). RESULTS: OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance. CONCLUSION: Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC.

Safety and Feasibility of Robotic Distal Gastrectomy for Stage IA Gastric Cancer: A Phase II Trial.

BACKGROUND: Conventional laparoscopic and open distal gastrectomy procedures have inherent limitations such as restricted movement of straight forceps and tremor of the tip of the devices that can potentially be overcome using robotic distal gastrectomy (RDG). This single-institutional phase II trial aimed to evaluate the safety and feasibility of RDG with lymph node dissection for clinical stage IA gastric cancer. METHODS: The study included patients with clinical stage IA gastric cancer in the lower two-thirds of the stomach considered to be curatively resected via distal gastrectomy. The primary end point was the proportion of patients who developed intra-abdominal complications, requiring medical or interventional treatment. The planned sample size was 25, calculated based on an expected complication rate of 3% and a threshold complication rate of 15%, with a one-sided alpha of 10%, power of 70%. RESULTS: Overall postoperative complications rate was 16%. The proportion of patients who developed intra-abdominal complications, requiring treatment was 0% (90% confidence interval, 0-9.8%). No patient developed in-hospital adverse events of grade 3 or higher. The short-term clinical outcomes were as follows: the median duration of postoperative hospital stay was 7 d, and 10 patients (40.0%) had a body temperature of 38°C or higher during their hospital stay. CONCLUSIONS: This trial confirmed the safety of RDG with limitation by the restriction of dedicated surgeons. A phase III trial to confirm the superiority of RDG to conventional laparoscopic distal gastrectomy is warranted.

A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: results of the KDOG1001 trial.

BACKGROUND: The prognosis of patients with gastric cancer with bulky node metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) remains poor. We conducted a phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for establishing a new treatment modality that improves prognosis. METHODS: Patients received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was administered for 1 year after surgical resection. The primary endpoint was the percentage of complete resections of the primary tumor with clear margins (R0 resection). The planned sample size was 40; this was calculated based on an expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of 5% and a power of 90%. RESULTS: Between 2010 and 2017, 40 patients were enrolled. The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade 3 histological response rate of 8%. CONCLUSIONS: Neoadjuvant chemotherapy with DCS was feasible and showed a sufficient R0 resection rate. A future study with a sufficient follow-up period should confirm survival outcomes.

Comparison of double-flap and OrVil techniques of laparoscopy-assisted proximal gastrectomy in preventing gastroesophageal reflux: a retrospective cohort study.

BACKGROUND: Laparoscopy-assisted proximal gastrectomy (LAPG) with esophagogastrostomy using the double-flap technique has been reported to rarely cause gastroesophageal reflux. However, quantitative evaluation of the reflux has hardly been performed. The aim of this study was to clarify the superiority of the double-flap technique of LAPG with esophagogastrostomy compared with the OrVil technique in terms of preventing gastroesophageal reflux. METHODS: A total of 40 and 51 patients who underwent LAPG with esophagogastrostomy using the double-flap and OrVil techniques, respectively, for upper one-third gastric cancer were included in this study. Of these, 22 and 13 patients in the double-flap and OrVil groups, respectively, consented to undergo a 24-h impedance-pH monitoring test at 3 months postoperatively. Postoperative complications, including gastroesophageal reflux and anastomotic stricture, were assessed retrospectively. RESULTS: No significant differences were observed in the patients' background between both groups, except for a higher D1+ dissection rate observed in double-flap group than in the OrVil group (93% vs 25%, P < 0.001). Operative time was significantly longer in the double-flap group than in the OrVil group (353 min vs 280 min, P < 0.001). All reflux % time was significantly lower in the double-flap group than in the OrVil group (1.29% vs 2.62%, P = 0.043). On the other hand, the proportion of anastomotic stricture requiring endoscopic balloon dilatation was lower in the double-flap group than in the OrVil group but without statistical significance (18% vs 27%; P = 0.32). CONCLUSIONS: Despite its longer operative time and still relatively high anastomotic stricture rate, the double-flap technique would be better than the OrVil technique in terms of preventing gastroesophageal reflux in patients who underwent LAPG with esophagogastrostomy.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.