[Two Cases of Chemotherapy after Self-Expandable Metallic Stent Placement for Obstructive Sigmoid Cancer with Unresectable Liver Metastasis].

Immediate decompression and induction of chemotherapy are exceedingly critical for obstructive colorectal cancer patients with unresectable liver metastasis. Systematic chemotherapy was administered after self-expandable metallic stent(SEMS) placement in 2 patients with obstructive sigmoid cancer with unresectable liver metastasis. Chemotherapy-induced tumor shrinkage led to SEMS migration, enabling the use of an anti-VEGF drug. Eventually, both patients underwent successful management without restenosis.

[A Case of Resection of Para-Aortic Lymph Node Recurrence following Rectal Cancer Surgery].

A 54-year old man diagnosed with rectal cancer underwent laparoscopic high anterior resection with Japanese D3 lymph node dissection. The pathology results were as follows: pT2pN3M0, pStage Ⅲb(Japanese Classification of Colorectal, 8th edition). Adjuvant chemotherapy with CapeOX regimen was administered 8 courses. 1.5 years after the operation, computed tomography(CT)examination revealed a swollen para-aortic lymph node(PALN). Positron emission tomography (PET)-CT revealed PALN with high FDG uptake. We considered that neo-adjuvant chemotherapy and PALN dissection may be possible for PALN, which was isolated metastasis and curative by surgery. After 6 courses of bevacizumab-FOLFIRI therapy was administered, PALN dissection was performed. Pathological examination of the resected specimen showed adenocarcinoma in 4 of the 16 dissected lymph nodes. Histological treatment effect of preoperative therapy was Grade 1b. Postoperatively 6 courses of FOLFIRI were administered. The patient has been followed up for 7 years and 8 months after the first surgery, 5 years and 9 months after the curative resection, with no recurrence showed complete cure. Multidisciplinary treatment with anticancer drug and R0 resection was an effective treatment for isolated PALN recurrence of rectal cancer.

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.

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.

[A Case of Recurrent Gastric Cancer with Clinical Complete Response after Ramucirumab plus Paclitaxel Therapy].

We report a case of a 61-year-old man who underwent open total gastrectomy and D2 lymph node dissection for gastric cancer. The pathological findings were suggestive of pT2N3M0, fStage ⅢA. S -1 was administered for 1 year post-surgery. One year and 9 months after the operation, an epigastralgia was found, and the PET-CT showed an increase of SUVmax 3.80 around the celiac artery. S -1 plus CDDP therapy was initiated. However, due to the occurrence of neutropenia, the therapy was changed to ramucirumab plus paclitaxel. After 20 courses of the same regimen, no PET-CT uptake was observed. We thus considered it cCR and discontinued further chemotherapy. The patient has been alive for 15 months without recurrence. By performing effective chemotherapy at an early stage, cCR could be observed after a secondary treatment. Therefore, longterm survival could be expected for post-operative recurrence of gastric cancer.

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.

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.

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.

Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis.

BACKGROUND: We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). METHODS: Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. RESULTS: PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor forming and invasive ability. CONCLUSION: Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.

Delta-shaped anastomosis vs circular stapler anastomosis after laparoscopic distal gastrectomy with Billroth I reconstruction: A randomized controlled trial.

INTRODUCTION: The aim of this study is to evaluate the efficacy of delta-shaped anastomosis compared to circular stapler anastomosis in laparoscopic distal gastrectomy with Billroth I reconstruction. METHODS: This is a single-center randomized controlled study. Eligibility criteria included histologically proven gastric adenocarcinoma in the lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to circular stapler anastomosis or delta-shaped anastomosis. The primary endpoint is the number of analgesics used during three days after surgery. We compared the surgical outcomes of the two groups. Postoperative quality of life was evaluated using the Postgastrectomy Syndrome Assessment Scale-45. This trial was registered at the UMIN Clinical Trials Registry as UMIN000025160. RESULTS: Between December 2016 and September 2018, 39 patients (delta-shaped anastomosis 18, circular stapler anastomosis 21) were enrolled. There was no difference in the number of analgesics used during three days after surgery (median nine: delta-shaped anastomosis vs nine: circular stapler anastomosis, P = .91). There was no difference in the overall proportion with in-hospital grade II-IIIB surgical complications (11%: delta-shaped anastomosis, 14%: circular stapler anastomosis). There was no operation-related death in either arm. Regarding postoperative quality of life evaluated one month after surgery, diarrhea subscale was significantly worse in delta-shaped anastomosis than in circular stapler anastomosis. CONCLUSION: We did not demonstrate the advantage of delta-shaped anastomosis in terms of postoperative pain. Since delta-shaped anastomosis tended to cause postoperative abdominal symptoms related to diarrhea, we should carefully apply the delta-shaped anastomosis to laparoscopic distal gastrectomy with Billroth I reconstruction.

Carcinosarcoma of the esophagus: A report of 6 cases associated with zinc finger E-box-binding homeobox 1 expression.

Esophageal carcinosarcoma (ECS) has been suggested to result from an epithelial mesenchymal transition (EMT) phenomenon. However, knowledge on its underlying molecular features is limited. The clinical and pathological features, and the prognosis of ECS require further investigation. In the present study, a total of 325 patients with esophageal tumors were observed between January 2004 and December 2014, of which 6 patients were diagnosed pathologically with ECS. The clinicopathological features were compared with those of corresponding cases with the identical pathological T stage (pT) of esophageal squamous cell carcinoma (ESCC). In terms of the clinical T stage (cT), the 6 cases were composed of cT1, cT2, cT3 and cT4 in 1, 1, 3 and 1 case, respectively. Nevertheless, pT was eventually diagnosed as pT1 in all cases. There was a large discrepancy between clinically diagnosed depth of tumor invasion prior to surgery and depth of tumor invasion following surgery. Zinc finger E-box-binding homeobox 1 (ZEB1), an EMT-associated transcription factor, was expressed only in the sarcoma component in all 6 cases of ECS. The ECS cases had a significantly poorer prognosis compared with the 115 pT1 ESCC cases. The present study suggests that the depth of invasion of ECS lesions does not correspond with their respective size, and the EMT of the carcinoma component may affect the prognosis by overexpression of the ZEB1 gene.

Cancer-specific promoter DNA methylation of Cysteine dioxygenase type 1 (CDO1) gene as an important prognostic biomarker of gastric cancer.

BACKGROUND: There have been few available prognostic biomarkers in gastric cancer. We rigorously assessed the clinical relevance of promoter DNA methylation of Cysteine dioxygenase type 1 (CDO1) gene, a cancer-specific aberration, in human gastric cancer. METHODS: Quantitative CDO1 methylation value (TaqMeth V) was initially calculated in 138 gastric cancer patients operated in 2005, and its clinical significance was elucidated. As a subsequent expanded set, 154 gastric cancer patients with pathological stage (pStage) II / III with no postoperative therapy were validated between 2000 and 2010. RESULTS: (1) Median TaqMeth V of CDO1 gene methylation of gastric cancer was 25.6, ranging from 0 to 120.9. As pStage progressed, CDO1 TaqMeth V became higher (p < 0.0001). (2) The optimal cut-off value was determined to be 32.6; gastric cancer patients with high CDO1 gene methylation showed a significantly worse prognosis than those with low CDO1 gene methylation (p < 0.0001). (3) A multivariate cox proportional hazards model identified high CDO1 gene methylation (p = 0.033) as an independent prognostic factor. (4) The results were recapitulated in the expanded set in pStage III, where high CDO1 gene methylation group had a significantly worse prognosis than low CDO1 gene methylation group (p = 0.0065). Hematogenous metastasis was unique in pStage III with high CDO1 gene methylation (p = 0.0075). (5) Anchorage independent growth was reduced in several gastric cancer cell lines due to forced expression of the CDO1 gene, suggesting that abnormal CDO1 gene expression may represent distant metastatic ability. CONCLUSIONS: Promoter DNA hypermethylation of CDO1 gene was rigorously validated as an important prognostic biomarker in primary gastric cancer with specific stage.

Prognostic relevance of FGFR2 expression in stage II/III gastric cancer with curative resection and S-1 chemotherapy.

Curative gastrectomy and adjuvant chemotherapy using S-1 is a standard treatment for stage II/III gastric cancer in Japan. The purpose of the present study was to evaluate the prognostic relevance of fibroblast growth factor receptor (FGFR)2 expression in patients with stage II/III gastric cancer that underwent postoperative adjuvant chemotherapy with S-1. Formalin-fixed paraffin-embedded surgical specimens were retrospectively examined in 167 patients with stage II/III gastric cancer that underwent curative gastrectomy followed by adjuvant S1 chemotherapy. FGFR2 expression was measured using immunohistochemistry (IHC) staining. The IHC results for FGFR2 were as follows: Grade 1+, 32; grade 2+, 80; grade 3+, 55 patients. The FGFR2 expression level was not significantly associated with relapse-free or overall survival rates. However, in the diffuse type, the FGFR2 expression level tended to be negatively correlated with relapse-free survival. In particular, the proportion of patients who recurred >5 years following surgery was significantly larger in the FGFR2 grade 3+ group than in the grade 1+, 2+ group (4/22 vs. 1/35; P=0.047). The recurrent sites of long-term failure were mostly peritoneum among the diffuse type. To the best of our knowledge, the present study indicated for the first time that FGFR2 could predict long-term failure of adjuvant S-1 chemotherapy in curative advanced gastric cancer. There was no interaction between FGFR2 expression and patient survival outcomes in stage II/III gastric cancer. Patients with FGFR2 3+ in stage II/III gastric cancer should carefully be followed-up for >5 years after surgery.

Prognoses of advanced esophago-gastric junction cancer may be modified by thoracotomy and splenectomy.

Globally, the incidence of esophago-gastric junction (EGJ) cancer is rapidly increasing. However, the proposed strategies for the treatment of these types of cancer are so diverse that there is no established consensus on the optimal treatment. The aim of the present study was to identify independent prognostic factors to delineate the optimal strategies for the treatment of EGJ cancer. The medical records of 150 patients with EGJ cancer who underwent curative surgery at the Kitasato University were retrospectively reviewed. The median follow-up period was 48 months. The patients with tumors that were classified as post-treatment primary tumor stage 3 [(y)pT3] or higher had a 5-year disease-specific survival (DSS) rate of 53%, whereas those with tumors that were classified as (y)pT0-2 had a 5-year DSS rate of 90%. Therefore, prognostic analysis was restricted to those tumors that were designated (y)pT3 or higher. A multivariate Cox's proportional hazards model identified the following independent prognostic factors that negatively influenced the DSS: i) Presence of tumors classified as post-treatment regional lymph node stage 1-3 [(y)pN1-3] [hazard ratio (HR), 3.62; 95% confidence interval (CI), 1.39-12.36]; ii) not undergoing treatment with splenectomy (HR, 2.40; 95% CI, 1.15-5.15); and iii) undergoing treatment with thoracotomy (HR, 2.07; 95% CI, 1.02-4.23). In patients with (y)pN0 tumors, the DSS rate was significantly improved for those who underwent splenectomy than for those who did not (P=0.024). In patients with (y)pN1-3 tumors, the DSS rate was significantly worse for those who underwent thoracotomy compared with those who did not (P=0.004). Splenectomy and thoracotomy may critically affect prognosis in locally advanced EGJ cancer that are classified as (y)pN0 and (y)pN1-3, respectively. Surgical treatments require optimization in order to improve prognoses in advanced EGJ cancer.

Optimized lymph node dissection range during progression of lower thoracic esophageal squamous cell carcinoma in the latest therapeutic surgical strategy: A retrospective analysis.

The distribution of lymph node metastases, including recurrences, remains elusive in lower thoracic esophageal squamous cell carcinoma (LtESCC). The present study was a retrospective investigation into the optimized lymph node dissection range during LtESCC. Esophagectomies were performed on 163 patients with ESCC between 2009 and 2016, among whom 41 patients with LtESCC were examined. The rates of pathological and potential (including recurrences) metastases to lymph nodes and the prognosis (median, 34 months) were determined. Preoperative Docetaxel, Cisplatin and 5-fluorouracil chemotherapy was administered in >60% of cStage II/III LtESCC. During stage progression, abdominal lymph node metastasis rapidly becomes aggressive in LtESCC and lymph node metastases to the para-aortic area were more dominant than cervical and recurrent laryngeal nerve (RLN) areas. There were few control failures of regional lymph node metastases in LtESCC with surgery, if 1 unique case with cStage III who had metastases and recurrences of multiple lymph nodes during the clinical course was excluded. Defective lymph node dissection around the RLN did not worsen LtESCC prognosis with no RLN palsy. In the context of the potent preoperative chemotherapy and esophagectomy, lymph node dissection of cervical, para-aortic and RLN areas are putatively not mandatory to all LtESCC patients.