Background Magnifying endoscopy has demonstrated dramatic morphologic changes in the surface microvasculature of superficial esophageal squamous cell carcinoma (ESCC) according to the depth of invasion. We investigated the mechanism of angiogenesis in early-stage ESCC by examining the expression of vascular endothelial growth factor (VEGF)-A and chondromodulin (ChM)-1. Methods Using 41 samples of superficial esophageal cancer (EP and LPM 19 cases, MM or deeper 22 cases) and 7 samples of regenerative squamous epithelium, the expression of VEGF-A and ChM-1 was examined in relation to the histological grade or morphology of the surface microvasculature demonstrated by magnifying endoscopy (types A, B, and C correspond to types A, B1, and B2 and B3 of the magnifying endoscopic classification of the Japan Esophageal Society, respectively). We also investigated the correlation between CD31-positive microvessel density (MVD) and VEGF-A or ChM-1 expression. Results In normal squamous epithelium, regenerative squamous epithelium, EP and LPM cancer, and MM or deeper cancer, the positivity rates for VEGF-A and ChM-1 were 0%, 85.7%, 52.6% and 90.9%, respectively, and 48.5%, 71.4%, 73.7% and 23.8%, respectively. The VEGF-A and ChM-1 positivity rates in type B or type C vasculature were 70.0% and 76.2%, respectively, and 75.0% and 19.0%, respectively. The expression of neither VEGF-A nor ChM-1 in cancer cells was correlated with MVD (P = 0.19 and 0.68, respectively), whereas that of VEGF-A in stromal mononuclear cells (SMCs) was significantly correlated with MVD (P = 0.04). Conclusion Angiogenesis at the early stage of ESCC progression is configured by the balance between accelerator (angiogenic factors from both cancer cells and SMCs) and brake (angiogenic inhibitor) factors.

By examining the reconstructed gastric tube during esophagectomy using indocyanine green fluorescence (ICG) angiography, we have established a '90-second rule' to confirm good blood perfusion at the anastomosis site. We examined the surgical outcome (rate of anastomotic leakage) of 70 consecutive patients who underwent esophagectomy with gastric tube reconstruction using ICG fluorescence angiography. All of the anastomoses were made in the area where less than 90 seconds was needed for enhancement using ICG fluorescence angiography (i.e. within the 90-second rule). In 18 cases for which the time until enhancement of the gastric tube tip exceeded 60 seconds, the anastomosis site was decided by reference to the ICG fluorescence angiogram, and the hypoperfused area was excised, and this significantly shortened the median time until enhancement of the gastric tube tip from 95.5 (60.0-204.0) seconds to 41.0 (9.0-77.0) seconds (P < 0.001). In three cases, the anastomosis was made at the site where more than 60 seconds was needed for ICG enhancement. In one case where ICG enhancement had taken 77 seconds, minor anastomotic leakage occurred. The overall rate of anastomotic leakage in this series was 1.4%. Blood flow in the reconstructed gastric tube is sufficient if the anastomosis is made in the area where ICG fluorescence angiography demonstrates enhancement within 60 seconds. Gastric tube necrosis can be avoided if the area showing an enhancement time exceeding 90 seconds is excised. The 90-second rule is a safe and effective method for deciding the site of anastomosis.

We conducted a detailed study of lymphangiogenesis and subsequent lymph node metastasis in early-stage esophageal squamous cell carcinoma (ESCC) using immunostaining for D2-40 and vascular endothelial growth factor (VEGF)-C and D. The study materials included 13 samples of normal squamous epithelium, 6 samples of low-grade intraepithelial neoplasia (LGIN), and 60 samples of superficial ESCC (M1 and M2 cancer 24; M3 or deeper cancer 36). We assessed lymphatic vessel density (LVD) using D2-40 and immunoreactivity for VEGF-C and D in relation to histological type, lymphatic invasion, and lymph node metastasis. LVD in M1 and M2 lesions and M3 or deeper lesions was significantly higher than in normal squamous epithelium (P < 0.001). High expression of VEGF-C and D was observed in M1 and M2 cancer and in M3 or deeper cancer, but not in normal squamous epithelium or LGIN. LVD in VEGF-C-and D-positive cases was significantly higher than in negative cases (P < 0.001). In M3 or deeper cancer, the correlation between VEGF-C or D status and lymphatic invasion or lymph node metastasis was not significant. LVD in cases with positive lymphatic invasion and those with lymph node metastasis was significantly higher than in cases lacking either (P = 0.02 and 0.03, respectively). ESCC cells produce VEGF-C and D from the very early stage of progression. VEGF-C and D activate lymphangiogenesis, and this increase of lymphatic vessels leads to lymphatic invasion and subsequent lymph node metastasis.

The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.

BACKGROUND/AIM:To evaluate the efficacy of conversion surgery following S-1 plus cisplatin (CS) or oxaliplatin (SOX) chemotherapy.PATIENTS AND METHODS:We retrospectively analyzed clinicopathological and survival data of 74 patients with unresectable gastric cancer receiving CS or SOX.RESULTS:Fifty-five and nineteen patients received CS and SOX, respectively. Conversion surgery (odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.64; p=0.01) was the only significant independent predictor of longer survival in multivariate Cox regression analysis. Patients (median age, 74 years) receiving SOX were significantly older than those receiving CS (median age=67 years) (p<0.01), although the rates of response, severe toxicity or conversion surgery did not differ significantly between the two treatment groups.CONCLUSION:Conversion surgery after a response to CS or SOX chemotherapy may have survival benefit in selected unresectable gastric cancer patients, for both non-elderly and elderly patients responding to SOX.

The purpose of this paper is to compare the oncologic outcomes between colorectal cancer (CRC) patients with tumor perforation and those with perforation proximal to the tumor. Medical charts of 39 patients who underwent emergency surgery for colonic perforation related to potentially curable CRC were reviewed. Eighteen patients developed tumor perforation (group A), whereas 21 patients developed perforation proximal to the tumor (group B). Twenty-four patients were pathologic stage II and 15 patients were stage III. There were no significant differences in the clinicopathologic and surgical data, including hospital mortality, between the groups; however, the incidence of diffuse peritonitis was higher in group B than that in group A (P < 0.01). The induction rates of adjuvant chemotherapy for survivors were identical between the 2 groups. Disease-free and overall survival periods did not significantly differ between the groups. Perforation type was not found to be associated with oncologic outcomes in patients with CRC-related perforation.

目的：直腸癌に対する括約筋温存術（sphincter preserving operation，SPO）時の側端吻合におけるsurgical site infection（SSI）と縫合不全，およびそれらのリスク因子について経腹的single stapling technique（SST）法と経肛門的double stapling technique（DST）法を比較検討した．

Background and study aims We report the features of a newly developed endocytoscopy system (ECS), the GIF-Y0074.Patients and methods The GIF-Y0074 offers high-definition resolution with a consecutive increase of magnification to x 500. Using ECS, we observed 32 cases of esophageal squamous cell carcinoma (ESCC), 11 cases of gastric cancer, and five cases of duodenal adenoma.Results The images of cells obtained using the GIF-Y0074 at maximum magnification were brighter and clearer than those obtained with previous ECS systems. For diagnosis of ESCC, clearer visualization of the nucleus made nuclear abnormality easier to recognize. Cancer cells were visualized in 10/11 cases of gastric cancer, but removal of mucus still remained a problem. Duodenal adenomas were found to have atypical cells with villi and tubules at the mucosal surface, thus assisting their histological diagnosis in vivo.Conclusion The GIF-Y0074 is an excellent ECS in terms of ease of use, satisfactory resolution, and magnification power, and therefore achieves a level of utility that makes its commercial release justifiable. This ECS heralds a new era of endoscopic and histological diagnosis.

Use of an endocytoscopy system (ECS) makes it possible to omit biopsy histology for esophageal squamous cell carcinoma (ESCC). However, for differential diagnosis of ESCC, the endocytoscopic characteristics of esophagitis should be clarified.

Aim: To identify the prognostic factors for gastric cancer with positive peritoneal cytology (CY1) or peritoneal metastasis (P1). Patients and Methods: We retrospectively analyzed clinicopathological and survival data of 78 patients who had undergone gastrectomy and/or S-1 based chemotherapy for CY1 or P1 gastric cancer. Results: The median overall survival (OS) did not differ significantly between patients with CY1P0, CY0P1 and CY1P1 disease (24, 17 vs. 14 months, respectively). Among 12 clinicopathological factors, clinical N3 (odds ratio [OR]=2.18; 95% confidence interval [CI]=1.22-4.00; p=0.01) and gastrectomy not performed (OR=1.80; 95% CI=1.29-2.51; p<0.01) were significant independent prognostic factors. The median OS significantly differed between patients who had undergone gastrectomy plus chemotherapy versus chemotherapy alone (22 vs. 10 months, respectively; p<0.01). Conclusion: Gastrectomy and perioperative chemotherapy may both be indicated in CY1 or P1 gastric cancer patients with clinical N0-2.

The association between angiogenesis and tumor-associated macrophages (TAMs) is unclear. Mononuclear cell infiltration was reported to induce angiogenesis in early stage esophageal squamous cell carcinoma (ESCC).

The objective of this study was to clarify the factors affecting blood flow at the tip of the gastric tube during esophagectomy using indocyanine green (ICG) fluorescence angiography. The time until enhancement of the gastric tube tip determined using ICG fluorescence imaging is a useful indicator of blood flow, and has been shown not to differ significantly according to the connection status of the right or left gastroepiploic artery. Using ICG fluorescence imaging, the time until enhancement of the gastric tube tip was measured in 50 patients undergoing esophagectomy. Blood flow at the gastric tube tip was compared between 2 groups of patients: those in whom a connecting vessel from the left gastro-epiploic artery to the short gastric artery (l-s GA) was present and those in whom it was absent. The factors affecting blood flow to the gastric tube tip were also investigated using univariate and multivariate logistic regression analysis. The median time taken for the gastric tube tip to show enhancement with ICG was significantly shorter in the group with an l-s GA connection (P = 0.02). Multivariate analysis showed that the absence of an l-s GA connection (P = 0.04) and presence of arteriosclerosis-related disease (P = 0.02) were significant independent factors that delayed blood flow to the gastric tube. It is essential to preserve the whole vessel arcade of the greater curvature to achieve good perfusion of the gastric tube with blood. The presence of arteriosclerosis-related disease is a major factor affecting the safety of anastomosis during gastric tube reconstruction.

AIMTo evaluate the efficacy and safety of nanoparticle albumin-bound-paclitaxel (nab-PTX) as second-line chemotherapy (CT) for patients with unresectable or recurrent gastric cancer (GC).PATIENTS AND METHODSThe clinicopathological and survival data of 37 patients with unresectable or recurrent GC who underwent nab-PTX monotherapy as second-line CT, were retrospectively analyzed.RESULTSThe median number of cycles and relative dose intensity administered per patient were 5 and 90%, respectively. Their overall response rate was 24.3% and the disease control rate was 59.5%. Median progression-free survival (PFS) and overall survival were 4.8 months and 10.4 months, respectively. Thirteen patients had grade 3 or 4 toxicities and were managed. In multivariate Cox regression analysis, cycles of chemotherapy ≥5 (odds ratio, 0.20; 95% confidence interval, 0.08-0.50; p<0.01) was the only significant independent predictor of longer PFS.CONCLUSIONNab-PTX may effectively prevent disease progression as second-line CT by increasing treatment cycles and managing adverse effects.

Aim: To evaluate the efficacy of protein-bound polysaccharide K (PSK) added to S-1 adjuvant chemotherapy for treatment of advanced gastric cancer. Patients and Methods: We retrospectively examined clinicopathological and recurrence-free survival (RFS) data for 136 patients with stage II or III advanced gastric cancer who underwent S-1 adjuvant chemotherapy with or without PSK. Results: Among 13 clinicopathological factors, non-T4 stage (odds ratio (OR)=0.61; 95% confidence interval (CI)=0.41-0.89; p<0.01), N0-1 (OR=0.65; 95% CI=0.43-0.95; p=0.03) and number of treatment cycles >= 7 (OR=0.37; 95% CI=0.200.67; p<0.01) were significant independent factors for better RFS. The number of treatment cycles of S-1 plus PSK was significantly higher than that of S-1 alone (p<0.01). Conclusion: S-1 adjuvant chemotherapy combined with PSK may reduce recurrence by prolonging the treatment cycles in patients with advanced non-T4 or N0-1 gastric cancer.

The clinical outcome and efficacy of postoperative chemotherapy in patients with Stage Ⅳ colorectal cancer with perforation were investigated. We compared the clinical outcomes between 11 patients with Stage Ⅳ colorectal cancer (perforation group), who underwent emergency surgery for colonic perforation between September 2005 and March 2012, and 22 matched patients (matching group) who underwent elective colorectal surgery during the same period. The colostomy rate in the perforation group was significantly higher than that of the matching group: patients with perforation received stoma construction surgery more frequently (p<0.01). Seven patients (64%) in the perforation group received postoperative chemotherapy, while 20 patients (91%) in the matching group received chemotherapy (p=0.15). Oxaliplatin-based chemotherapy was administered to all patients in both groups. There was no difference in the median relative dose intensity of oxaliplatin between these groups (p=0.37). No significant difference was observed between the cumulative 3-year overall survival rate in the perforation group and that of the matching group (35% and 54%, respectively; p=0.35). Moreover, the 3-year overall survival rates of patients who received oxaliplatin-based chemotherapy were 51%in the perforation group and 57% in the matching group (p=0.74). Our results suggest that postoperative oxaliplatin-based chemotherapy may improve the prognosis of patients with Stage Ⅳ colorectal cancer with perforation.

Using immunohistochemical staining, the present study was conducted to examine whether cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) affect angiogenesis in early-stage esophageal squamous cell carcinoma (ESCC). We also analyzed the correlation between these two factors. Cyclooxygenase 2, iNOS, and angiogenesis in early-stage ESCC are unclear. Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia (LGIN), and 45 samples of superficial esophageal cancer, we observed the expression of COX-2 and iNOS. We then investigated the COX-2 and iNOS immunoreactivity scores and the correlation between COX-2 or iNOS scores and microvessel density (MVD) using CD34 or CD105. The intensity of COX-2 or iNOS expression differed significantly according to histological type (P < 0.001). The scores of COX-2 and iNOS were lowest for normal squamous epithelium, followed in ascending order by LGIN, carcinoma in situ and tumor invading the lamina propria mucosae (M1-M2 cancer); and tumor invading the muscularis mucosa (M3) or deeper cancer. The differences were significant (P < 0.001). Cancers classified M1-M2 (P < 0.01 and P < 0.05, respectively); M3; or deeper cancer (P < 0.01) had significantly higher COX-2 and iNOS scores than normal squamous epithelium. There was a significant correlation between COX-2 and iNOS scores (P < 0.001, rs = 0.51). Correlations between COX-2 score and CD34-positive MVD or CD105-positive MVD were significant (rs = 0.53, P < 0.001; rs = 0.62, P < 0.001, respectively). Inducible nitric oxide synthase score was also significantly correlated with CD34 MVD and CD105 MVD (rs = 0.45, P < 0.001; rs = 0.60, P < 0.001, respectively). Chemoprevention of COX-2 or iNOS activity may blunt the development of ESCC from precancerous lesions.

【目的】直腸癌の括約筋温存手術における，closed suction drainの縫合不全に対する意義について後方視的に検討した．さらに，縫合不全の危険因子についても検討した．【対象・方法】直腸癌に対する括約筋温存手術において，仙骨前面にclosed suction drainを留置した連続151例を対象．縫合不全の頻度，治療，ドレーン排液量の推移，縫合不全の危険因子について検討した．縫合不全の分類はInternational Study Group of Rectal Cancer（ISREC）groupのGrade分類に従った．【結果】縫合不全は６例（4.0％）に認めた．縫合不全のGradeはA ３例，B １例，C ２例であった．縫合不全の部位が吻合部後壁の３例ではすべてGrade A，側端吻合の口側大腸断端の１例ではGrade B，吻合部前壁の２例ではいずれもGrade Cであった．ドレーン排液量は，縫合不全症例の方が，非縫合不全症例より第１病日までの排液量が多かった（p＝0.04）が，第２病日，第３病日の排液量に差はなかった．縫合不全の危険因子について，ロジスティック回帰分析を行ったところ，単変量解析では側方郭清施行（p<0.01），ドレーン抜去日６日目以降（p＝0.06）が選択され，多変量解析では側方郭清（p＝0.04）のみが縫合不全の危険因子として同定された．【結語】直腸癌に対する括約筋温存手術においてclosed suction drainは，縫合不全発生率とのバランスから考えれば有用性は限定的である．

Aim: To evaluate the recurrence risk for Siewert type II esophagogastric junction carcinoma treated with curative resection. Patients and Methods: We retrospectively analyzed clinicopathological and recurrence-free survival (RFS) data of 52 patients after curative resection for Siewert type II carcinoma focusing on the role of lymph node metastasis around the greater curvature or parapyloric area. Results: Recurrence was observed in 21 (40%) patients; the median time-to-recurrence was 11 months (range=3-33 months). According to multivariate Cox proportional hazard regression analysis, involvement of nodes no. 4sa, 4sb, 4d, 5 and/or 6 (odds ratio (OR)=6.62; 95% confidence interval (CI)=1.27-41.1; p=0.04) and younger age (OR=2.10; 95% CI=1.25-3.82; p<0.01) were significant independent risk factors affecting RFS. Conclusion: Involvement of no. 4-6 nodes appears to predict recurrence of Siewert type II carcinoma treated with curative resection. Patients with this risk factor may benefit from effective use of perioperative chemotherapy.

INTRODUCTION:Reports on pancreas-preserving total duodenectomy (PPTD) for duodenal polyposis (DP) in familial adenomatous polyposis (FAP) patients are rare. We herein report a case of PPTD performed by minilaparotomy for DP in an FAP patient.CASE:A 27-year-old female FAP patient was diagnosed with Spigelman classification (SC) stage Ⅳ DP on gastroduodenoscopy. She underwent PPTD through a 7 cm upper abdominal incision. All polyps were confirmed as adenomas histopathologically. After 6 months of follow-up, complications related to total duodenectomy, such as weight loss, diabetes mellitus, and fatty liver have not been observed.DISCUSSION:SC stage Ⅳ refers to non-advanced cancers, and PPTD is basically prophylactic surgery. Therefore, pancreatoduodenectomy seems too aggressive for SC stage Ⅳ patients. PPTD by minilaparotomy is suitable for young female patients for its curability, esthetic outcome, and safety.