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A 57-year-old woman was admitted to our hospital for treatment of gastric cancer presenting as a type 2 tumor in the lower third of the stomach. According to pre-therapeutic imaging examinations and laparoscopy, she was diagnosed with advanced gastric cancer, cT4a(SE)N2M0, Stage Ⅲ. Therefore, neoadjuvant chemotherapy was planned, and she received the SOX regimen. After 3 courses of chemotherapy, post-therapeutic imaging examinations showed that the primary gastric tumor and metastatic lymph nodes had reduced in size. We performed distal gastrectomy with D2 lymphadenectomy. Final pathological examinations demonstrated that no viable tumor cells remained in the resected stomach and dissected lymph nodes (Grade 3). SOX may be useful as neoadjuvant chemotherapy to improve prognosis in patients with advanced gastric cancer. Herein, we report a case of advanced gastric cancer with pathological complete response after neoadjuvant chemotherapy with the SOX regimen.

Background/aim: We previously described the safety of distal jejunal pouch with Roux-en-Y reconstruction after total gastrectomy. The present prospective study evaluated its clinical benefit., Patients and Methods: Forty-five patients with gastric cancer were preoperatively assigned to groups who underwent Roux-en-Y reconstruction with jejunal pouch (PRY) (n=23) or without pouch (RY) (n=22). Age, sex, grade of lymph node dissection, splenectomy and mode of laparotomy were analyzed, and body mass index (BMI), volume of food intake at one sitting and blood chemistry (total protein, hemoglobin, iron and cholesterol) were periodically assessed in both groups., Results: Post-surgical mortality and severe morbidity did not occur. Three and four patients in the PRY and RY groups, respectively, died of gastric cancer recurrence during the study. BMI at six months after surgery was significantly higher in the PRY than in the RY group (p<0.05). The percentage of food intake at one year after the procedure was significantly higher in the PRY than in the RY group (p<0.05)., Conclusion: The distal jejunal pouch ameliorated postoperative weight loss and increased food intake. A distal jejunal pouch with PRY reconstruction may confer significant clinical advantages after total gastrectomy. The long-term clinical benefit of this procedure should be evaluated., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The sentinel node (SN) detection by dual tracer method using indocyanine green (ICG) and a radioisotope (RI) has been recommended for early gastric cancer. However, institutions are limited due to radioactivity in the RI method. The greatest advantage of the RI method is that it objectively assesses RI uptake as a numerical value. The aim of the present study was to verify the usefulness of ICG fluorescence intensity in SN., Methods: Seventeen patients with early gastric cancer were enrolled in this study. RI uptake by each lymph node was measured using Navigator GPS and fluorescence nodes were identified using the hyper eye medical system (HEMS). Fluorescence intensity in fluorescence nodes was evaluated using ICG intensity imaging software (Mizuho, Japan) of the HEMS., Results: The total number of dissected lymph nodes was 227, with an average of 13.3 per patient. The numbers of HN, FN-S, and FN-B were 64, 77, and 34. RI uptake was significantly greater by FN-S than by non-FN-S (P = 0.0016). The median fluorescence intensity value was higher in HN than in non-HN (P < 0.001). A correlation was observed between RI uptake and fluorescence intensity. Dissecting FNs with fluorescence intensity levels of 1-6 resulted in 92.1% dissection of HNs., Conclusion: It is possible that the evaluation of fluorescence intensity is useful for selected SNs instead of RI tracer. If fluorescence intensity is measurable in surgery, an infrared fluorescence method using ICG may be useful and safe for the detection of SN in early gastric cancer.

Background: Sex-determining region Y-box 9 (SOX9) is an important transcription factor for the development and differentiation of cells and their organization. In the present study, the clinical significance of SOX9 expression in oesophageal squamous cell carcinoma was examined., Materials and Methods: SOX9 expression in surgical specimens of primary tumours were immunohistochemically investigated in 175 patients with oesophageal squamous cell carcinomas., Results: SOX9 was expressed (moderately or strongly) in 62.9% of samples. Expression of SOX9 was significantly positively correlated with depth of invasion, advanced stage, lymphatic and venous invasion, and poor prognosis. Univariate analysis showed that depth of invasion, lymph node metastasis, distant metastasis, stage, lymphatic invasion, venous invasion, and SOX9 expression were prognostic factors. Multivariate analysis indicated that depth of invasion and stage were independent prognostic factors, but SOX9 expression was not., Conclusion: SOX9 expression is related to prognosis in patients with oesophageal squamous cell carcinoma, although it is not an independent prognostic factor., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor. Untreated peripheral blood specimens were obtained from 111 patients with gastric cancer and 20 healthy volunteers. HHLA2 mRNA expression levels were determined using quantitative RT-PCR assay. Blood specimens obtained from patients with gastric cancer had significantly lower copies of HHLA2 mRNA than those obtained from healthy volunteers ( P < 0.0001). Furthermore, HHLA2 expression was significantly correlated with the depth of tumor invasion ( P = 0.0331), distant metastasis ( P < 0.0001), and stage of disease ( P = 0.0032). The 5-year survival rate was significantly higher in patients with high HHLA2 expression compared with the patients with low expression ( P = 0.0001). These findings demonstrate that assessment of HHLA2 expression levels in the blood could be utilized to predict tumor aggressiveness in patients with gastric cancer., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Rationale: Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function., Objective: To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure., Methods and Results: We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes., Conclusions: CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750., (© 2018 American Heart Association, Inc.)

Background: Almost all reports on cardiac regeneration therapy have referred to adults, and only a few have focused on transcoronary infusion of cardiac progenitor cells using the stop-flow technique in children., Methods: Intracoronary autologous cardiosphere-derived cell (CDC) transfer was conducted at Okayama University as a phase 1 clinical trial for seven patients with hypoplastic left heart syndrome between January 2011 and December 2012, and as a phase 2 clinical trial for 34 patients with single-ventricle physiology between July 2013 and March 2015., Results: A total of 41 patients with single-ventricle physiology underwent transcoronary infusion of CDC with the stop-flow technique. The median age was 33 months (range, 5-70 months) and the median weight was 10.1 kg (range, 4.1-16.0 kg). Transient adverse events occurred during the procedure, including ST-segment elevation or depression, hypotension, bradycardia, and coronary artery vasospasm. All patients completely recovered. There were no major procedure-related adverse events. In this study, transcoronary infusion of CDC using the stop-flow technique was successfully completed in all patients., Conclusion: Transcoronary infusion of CDC using the stop-flow technique in children is a feasible and safe procedure., (© 2017 Japan Pediatric Society.)

Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis. This study assessed the clinical significance of PD-L1 mRNA expression in blood specimens obtained from patients with gastric cancer. Peripheral blood specimens were collected before treatment from 124 patients with gastric cancer. The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death-ligand 1 mRNA expression was significantly higher in patients with advanced gastric cancer than in patients with early gastric cancer (P = .002). Moreover, PD-L1 expression correlated significantly with depth of tumor invasion, distant metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients with high PD-L1 expression showed significantly poorer prognosis than those with low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1 expression as an independent prognostic factor. Expression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

As an antagonist of bone morphogenetic proteins (BMPs), 2, 4 and 7, gremlin1 plays a role in regulating organogenesis, tissue differentiation and angiogenesis. However, there is little information regarding gremlin1 in gastrointestinal cancer. We attempted to clarify how gremlin1 expression affects the clinical features and biological properties of gastric cancer. A total of 232 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were enrolled. Gremlin1 expression in gastric cancer was detected by immunohistochemical and western blotting methods. Correlations between clinicopathological parameters and gremlin1 expression were analyzed. Gremlin1 was identified in the cytoplasm and nucleus of all gastric cancer cell lines and some regions of surgical specimens of gastric cancer. One hundred and seventeen of the 232 patients (50.4%) were classified as gremlin1-positive based on gremlin1 expression. Gremlin1 positivity was correlated with shallower tumor depth, smaller tumor size, less nodal involvement and vessel invasion (p < 0.05). The 5-year survival rate of the gremlin1-positive group was 81%, which was significantly higher than the gremlin1-negative group (p < 0.01). Multivariate analysis revealed that gremlin1 was not selected as an independent prognostic marker. Gremlin1 expression in gastric cancer may be a useful prognostic marker that is involved with the BMP signaling pathway. Furthermore, gremlin1 may have clinical use as a diagnostic and treatment tool.

Background: While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not., Methods: Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis., Results: The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor., Conclusion: Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

Although postoperative management of gastric cancer is determined by pathological stage based on the tumor-node-metastasis classification, predicting disease recurrence and prognosis in patients undergoing gastrectomy is clinically difficult. We investigated the depth of tumor invasion and tumor size in resected specimens from patients with gastric cancer and assessed the clinical utility of primary tumor score (PTS) calculated by tumor depth and size as a prognostic marker. We classified 247 patients with gastric cancer into three groups based on cut-off values for deeper tumor invasion (pT2-T4) and larger tumor size (≥ 45 mm) as a PTS of 2 (both abnormalities), 1 (one abnormality), or 0 (neither abnormality). PTS correlated significantly with lymph node metastasis, lymphovascular invasion, and stage ( P < 0.0001 each). Survival differences among groups based on PTS were significant ( P < 0.0001). Multivariate analysis identified PTS alone as an independent prognostic factor ( P = 0.0363). PTS derived from primary tumor information alone is a potentially useful marker for predicting tumor progression and prognosis in postoperative patients with gastric cancer., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Background: Perforation of the horizontal duodenum is very rare due to the presence in retroperitoneal space. It depicts an unusual clinical picture and is difficult to diagnose, leading to increased morbidity and mortality. The treatment strategies are usually varied and based on small series of cases, literature reviews, and expert opinions., Case Presentation: Here, we presented three cases of horizontal duodenal perforation in three different clinical processes. The first case, a 30-year-old male patient, presented with abdominal pain and hematemesis after experiencing a physical assault on the previous day. Computed tomography (CT) scan showed rupture of the horizontal duodenum. It was repaired by side-to-side duodenojejunostomy. Postoperatively, he had anastomotic leakage, disseminated intravascular coagulation, and pulmonary failure and recovered after a long hospital stay. The second case, an 81-year-old female, had duodenal perforation with endoscopic coagulation of the bleeding diverticulum. Segmental resection of the duodenum and side-to-side duodenojejunostomy were performed. Postoperatively, there was slight anastomotic leakage, but surgical intervention was not needed. The third case, an 89-year-old female, was a patient with obstructive jaundice due to pancreas head carcinoma, who developed perforation of the horizontal duodenum during endoscopic retrograde cholangiopancreatography (ERCP). After unsuccessful conservative management, duodenojejunostomy at the perforated site and gastric bypass were performed. The postoperative course was uneventful., Conclusion: Early suspicion and investigation is necessary for cases of abdominal injuries. CT scan is the investigation of choice. The management options should be based on the clinical condition of the patient, comorbidities, surgical expertise, existing guidelines, and available resources.

Sentinel node navigation surgery (SNNS) has been recognized as a minimally invasive tool for individualized lymphadenectomy in patients with early gastric cancer (EGC). The aim of this study was to compare clinicopathological factors, adverse events, and clinical outcomes between sentinel node mapping (SNM) and SN dissection (SND) groups and assess the clinical utility of SNNS in patients with EGC. The clinical data of 157 patients with EGC, diagnosed as clinical T1N0M0 with tumors ≤ 40 mm, undergoing SNNS between March 2004 and April 2016 were retrospectively reviewed. Twenty-seven patients were excluded from the analysis. In the remaining 130 patients, 59 and 71 patients underwent standard lymphadenectomy for SNM and SND, respectively. The sentinel node detection rate in the SNM and SND groups was 98.3% (58/59) and 100% (71/71), respectively. Two (3.5%), 15 (25.9%), and 41 (70.7%) patients having sentinel nodes underwent total gastrectomy, proximal gastrectomy (PG), and distal gastrectomy (DG), respectively, in the SNM group. One (1.4%), 5 (7.0%), 10 (14.1%), 39 (54.9%), and 16 (22.5%) patients underwent PG, DG, segmental gastrectomy, local resection, and endoscopic submucosal dissection, respectively, in the SND group. There was no significant difference in postoperative complications between the SNM and SND groups ( P = 0.781). Survival did not differ between the both groups ( P = 0.856). The present results suggest that personalized surgery with SND provides technical safety and curability related with a favorable survival outcome in patients with EGC., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Rationale: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure., Objective: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology., Methods and Results: We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P =0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P <0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P <0.0001) and volumes ( P <0.001), somatic growth ( P <0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status ( P <0.0001) and cardiac fibrosis ( P =0.014) relative to baseline., Conclusions: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750., (© 2017 American Heart Association, Inc.)

Background: Cysteine/histidine-rich 1 (CYHR1) was first discovered in a yeast two-hybrid screen with murine galectin-3, and no previous reports have described a relationship between the CYHR1 gene and human cancer. The current study evaluated the role and significance of CYHR1 in esophageal cancer., Methods: The human esophageal squamous cell carcinoma (ESCC) cell line TE-8 and the CYHR1 knock-down cell line TE-8/small interfering (si)-CYHR1 were used for in vitro and in vivo assays. For clinical study, ESCC tissues (n = 104) were used., Results: Compared with parental cells, TE-8/si-CYHR1 cells had suppressed proliferation and invasion activities. In the in vivo assay, the tumors from TE-8 cells treated with si-CYHR1 had abrogated tumorigenicity. In the clinical study, the expression of CYHR1 mRNA was associated with lymph node metastasis and stage and shown to be an independent prognostic factor., Conclusions: As the findings show, CYHR1 may represent not only a valuable prognostic marker but also a therapeutic target for ESCC patients.

Patients with advanced esophageal squamous cell carcinoma (ESCC) is received chemoradiotherapy or chemotherapy for clinical management. However, it is difficult to predict tumor response and prognosis using blood markers before starting treatments. The purpose of this study was to investigate the pre-treatment plasma fibrinogen and neutrophil-lymphocyte ratio (NLR) in patients with advanced ESCC treated with chemoradiotherapy or chemotherapy, and to assess the clinical utility of a combined score using these blood markers, named as the F-NLR (fibrinogen and NLR) score, as a predictor of tumor response and prognosis. A total of 98 advanced ESCC patients, treated with chemoradiotherapy or chemotherapy, were classified into three groups: F-NLR score of 2, having both hyperfibrinogenemia (>400 mg/dL) and high NLR (>3.0), score of 1, one of these hematological abnormalities, and score of 0, having neither hyperfibrinogenemia nor high NLR. Fibrinogen and NLR were significantly higher in the progressive disease (PD) group than the non-PD group (P = 0.0419, and P = 0.0001, respectively). A significantly higher F-NLR score was found in the PD group than the non-PD group (P = 0.0140). Overall survival was significantly lower in patients with an F-NLR score of 2 than in those with an F-NLR score of 0 or 1 (P < 0.0001). Multivariate analysis showed that the F-NLR score was one of the independent prognostic factors (P = 0.0081). Our study demonstrates that the F-NLR score is promising as a predictive marker for therapeutic effects and prognosis in patients with advanced ESCC., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Advanced gastric cancer in the lower third of the stomach often results in stricture of the gastric cavity and digestive symptoms. Gastrojejunostomy has been suggested to improve such symptoms, and the advent of new anticancer agents for gastric cancer has improved the response rate of the disease, which makes it possible to perform R0 gastrectomy in part of patients with stage IV gastric cancer. We experienced a rare case in which a patient with stage IV gastric cancer and cancerous pyloric stenosis was treated with R0 surgery after undergoing a gastrojejunal bypass procedure and multidisciplinary treatment. There have not been any previous reports about cases in which a previous gastrojejunostomy was utilized as a reconstruction route during distal gastrectomy in a patient with gastric cancer that had been treated with chemotherapy and/or CRT., Case Presentation: An 80-year-old female with advanced gastric cancer and pyloric stenosis was admitted to Kagoshima University Hospital. As peritoneal washing cytology produced a positive result, laparoscopic gastrojejunostomy (modified Devine procedure) was performed to improve food passage, and S-1 (100 mg/body, days 1-14) plus paclitaxel (120 mg/body, days 1 and 15) was administered. Although the tumor was temporarily reduced in size, an abdominal computed tomography scan obtained after four courses of chemotherapy showed progressive disease. Thus, chemoradiotherapy (56 Gy, S-1: 60 mg/body, CDDP: 5 mg/body, days 1-5) was indicated. Marked tumor shrinkage and negative peritoneal washing cytological results were achieved. Curative gastrectomy with D2 lymphadenectomy was performed. We carried out distal gastrectomy and lymph node dissection, and the gastrojejunostomy produced as a gastric bypass in the previous operation was preserved. The patient has not suffered a tumor relapse in 4 years since the surgery., Conclusions: We surgeons increase a chance to perform R0 gastrectomy for stage IV gastric cancer following intensive chemotherapy and/or CRT. We should choose proper position of gastrojejunostomy in producing alimentary bypass for stage IV gastric cancer patients to facilitate curative surgery.

Aim: To assess the clinical utility of the Glasgow prognostic score (GPS) as a blood predictor of postoperative recurrence in patients with gastric gastrointestinal stromal tumors (GISTs)., Patients and Methods: Twenty-nine patients with gastric GISTs undergoing gastrectomy were retrospectively reviewed. Patients were classified based on GPS criteria as follows: GPS of 2: elevated C-reactive protein (>1.0 mg/dl) and hypoalbuminemia (<3.5 g/dl), GPS of 1: one of these hematological abnormalities, and GPS of 0: neither elevated CRP nor hypoalbuminemia., Results: The National Institutes of Health (NIH) classification for a risk stratification demonstrated that 3 (10.3%), 15 (51.7%), 5 (17.2%), and 6 (20.7%) patients were at very low, low, intermediate, and high risk, respectively, of disease recurrence. GPS criteria classified 24 (82.8%), five (17.2%), and no (0%) patients into GPS of 0, 1, and 2, respectively. Postoperative recurrence was identified in five patients (17.2%). Disease recurrence correlated with a risk stratification based on the NIH or GPS classification (p=0.004 and p=0.024, respectively)., Conclusion: The GPS, as well as NIH classification, is a promising blood predictor of disease recurrence in patients with resectable gastric GISTs., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: Therapeutic mammoplasty (TM) for breast cancer is a widely practiced oncoplastic technique. Intraductal spread towards the nipple or the location of the cancerous lesion on the central breast may become a contraindication for breast-conserving surgery. We herein report the results of TM in such cases., Methods: Six patients underwent TM that combined partial mastectomy with free nipple-areola (NA) grafting. The nipple was removed together with the cancerous lesions, and the areola was preserved for NA reconstruction. The tumors were located in the lower quadrant (n = 1), the central area (n = 1), the upper-outer area (n = 2), and the upper-inner area (n = 2). The types of mammoplasty that were performed included: amputation (n = 1), inverted T mammoplasty (n = 3), and L mammoplasty (n = 2). With the exception of one patient, all patients underwent inverted T mammoplasty on the contralateral breast in order to achieve symmetry., Results: The total surgical and plastic periods ranged from 155 to 235 min (mean 207 min) and 100 to 150 min (mean 121 min), respectively. Oncological safety and excellent cosmetic results were achieved., Conclusions: TM combining partial mastectomy with NA grafting was successfully performed in patients with early-stage cancer in all quadrant areas.

Aim: To compare adverse events and post-therapeutic clinical courses between stomach-partitioning gastrojejunostomy with Braun enteroenterostomy (SPGJ-BEE) and endoscopic metallic stent placement (EMSP) in patients with gastric outlet obstruction (GOO) caused by unresectable gastric cancer and assess the clinical utility of SPGJ-BEE., Patients and Methods: We retrospectively reviewed clinical data of 16 and 9 patients with GOO undergoing SPGJ-BEE and EMSP, respectively., Results: Re-obstruction caused by tumor overgrowth was identified in 3 (33.3%) out of 9 patients in the EMSP group. The GOO scoring system (GOOSS) revealed that its score after treatments was significantly higher in the SPGJ-BEE group than in the EMSP group (p<0.001). All patients in both groups received chemotherapy after treatments. The median survival times in the SPGJ-BEE and EMSP groups were 414 and 303 days, respectively., Conclusion: Our preliminary results suggest that SPGJ-BEE provides an improved long-term quality of life and the early induction of subsequent chemotherapy related with a better prognosis in patients with GOO., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The necessity of surgical treatment of liver metastases of gastric cancer is still controversial., Patients and Methods: We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria., Results: Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival., Conclusions: To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

The percentage of gastroduodenal neuroendocrine tumors (NETs) among all gastroenteropancreatic (GEP) NETs has gradually increased worldwide. Sentinel node navigation surgery (SNNS) has been developed as a personalized approach in the surgical strategy for early gastrointestinal tract cancers. We herein report 2 cases of gastroduodenal NETs treated with SNNS. Technetium-tin colloid including indocyanine green was endoscopically injected into the submucosa around a tumor the day before surgery. Basin dissection including the sentinel nodes (SNs), which were identified by Navigator GPS and near-infrared fluorescence imaging, was performed during laparoscopic surgery. SNs were intraoperatively examined using hematoxylin-eosin (HE) staining.SNs were detected in 2 patients. Lymph node metastasis was intraoperatively identified in 1 of the 2 patients. Consequently, 1 patient with metastatic SNs underwent laparoscopic gastrectomy with lymphadenectomy. Pathological findings identified submucosal NET measuring 6.0 mm × 5.0 mm.Our results suggest that SNNS is a promising surgical tool for detecting subclinical lymph node metastasis in patients with gastroduodenal NETs.

A 51-year-old man who had undergone distal gastrectomy for gastric cancer was admitted in Kagoshima University Hospital under the diagnosis of anastomotic recurrence of gastric cancer. From abdominal CT results, the recurred tumor was suspected to invade into the pancreas with regional node metastases. Because of the intense radicality of surgical intervention, we planned 3 courses of docetaxel, cisplatin, and S-1 triplet therapy(DCS therapy). After the chemotherapy, the recurred tumor and lymph node metastases shrunk drastically. Segmental gastrectomy with lymph node dissection was performed with curative intent. Final pathology revealed complete regression of both the recurred tumor and lymph node metastases. The patient's postoperative course was uneventful without tumor relapse. DCS therapy seems to be suitable to obtain drastic tumor regression before surgical intervention as a neoadjuvant chemotherapy for locally advanced gastric cancer.

The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT 3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT 3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC.

Background: The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses., Methods: A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer., Results: SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively., Conclusions: The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer., (© 2015 American Cancer Society.)

Certain patients with early gastric cancer succumb to recurrent disease and cancer-associated complications. The key cause of recurrence is challenging to determine, since clinical blood markers that are able to predict the tumor properties of gastric cancer are limited. The present study investigated the fibrinogen concentration and neutrophil-lymphocyte ratio (NLR) in blood specimens from patients with gastric cancer, and assessed the clinical applicability of combining the fibrinogen concentration with the NLR (CFS-NLR) as a prognostic marker of gastric cancer. The present study consisted of 275 patients with gastric cancer, who were divided into three groups: Those possessing hyperfibrinogenemia (≥305 mg/dl) and a high NLR (≥2.34; CFS-NLR 2 group); those possessing either hyperfibrinogenemia or a high NLR (CFS-NLR 1 group); or those that possessed neither abnormality (CFS-NLR 0 group). The CFS-NLR was significantly associated with the depth of tumor invasion, lymph node metastasis, lymphovascular invasion and tumor stage (P<0.0001). The prognostic differences among the three groups were significant (P=0.0016). Therefore, the CFS-NLR may be a potentially useful blood marker for predicting tumor progression and the prognosis of patients with gastric cancer.

Objective: We assessed the clinical applicability of the F-NLR score, which is based on fibrinogen (F) and the neutrophil-lymphocyte ratio (NLR), and the Glasgow Prognostic Score (GPS) to predict the therapeutic effects of chemotherapy or chemoradiotherapy on advanced gastric cancer and the prognoses of patients., Methods: Sixty-eight patients with advanced gastric cancer treated with first-line chemotherapy or chemoradiotherapy were classified into two groups based on tumor response. Furthermore, we categorized patients according to cutoff F-NLR scores of 2 [hyperfibrinogenemia (>400 mg/dl) and high NLR (>3.0)], 1 [one of these hematological abnormalities], and 0 [neither hyperfibrinogenemia nor high NLR]., Results: A total of 27 patients had progressive disease (PD) and 41 did not. The F-NLR scores were significantly higher in the PD than in the non-PD group (p = 0.003). Survival was significantly shorter for patients with high F-NLR scores and GPS (p = 0.0071 and p = 0.0065, respectively). Multivariate analysis selected the F-NLR score as an independent prognostic factor (p = 0.017)., Conclusion: A novel grading system based on F-NLR scores, as well as the GPS, appears to have value as a clinical predictor of the therapeutic response of advanced gastric cancer to chemotherapy or chemoradiotherapy and the prognoses of patients., (© 2016 S. Karger AG, Basel.)

Background: Ferredoxin reductase (Fdxr) is the mitochondrial cytochrome P-450 NADPH reductase. Fdxr overexpression increases the sensitivity of tumor cells to apoptosis in response to chemotherapy through reactive oxygen species (ROS) production. The aim of the present study was to examine the Fdxr expression in esophageal squamous cell carcinoma (ESCC) and determine if the expression is useful for predicting response to chemoradiation therapy (CRT)., Materials and Methods: Fdxr expression in biopsy specimens from 50 patients before neoadjuvant CRT were immunohistochemically examined. Then, the correlation between Fdxr expression and response to CRT were analyzed., Results: Both clinically and histologically, significant correlations were found between positive Fdxr expression and favorable response to CRT. Furthermore, Fdxr was significantly correlated with postoperative outcomes and was found to be an independent prognostic factor., Conclusion: Fdxr expression was found to be closely related to the effect of CRT and could predict the CRT outcome in patients with ESCC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS)., Methods: In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up., Results: No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion., Conclusions: Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the maintenance of volume as a spacer by comparing vascular supply and apoptosis in an implanted autologous-free dermal fat graft (FDFG) and free fat graft (FFG). An autologous FDFG is a material used in plastic surgery and oncoplastic breast surgery that is ideal for immediate volume replacement after partial mastectomy because of its easy availability and minimal invasion of the donor site; however, immunohistochemical findings and survival procedures have not yet been reported., Methods: An experimental protocol using a unique animal model was designed for the present study. The expression of vascular endothelial growth factor (VEGF) was measured in FDFGs and FFGs implanted onto the pectoral major muscle of Wistar rats. Thirty Wistar rats were divided into two groups and postoperatively 1, 2, 4, 8, and 16 weeks (POW1, 2, 4, 8, 16). Six samples from three rats in each group were used as control samples (POW0)., Results: The thickness of the implanted FDFG was not significantly different from the control sample at POW1, 2, 4, 8, and 16 between FDFG and FFG group; however, the thickness at POW8 and 16 was significantly lesser in the FFG group than in the control samples. The average proportion of fatty tissue to whole tissue ranged from 34.2 to 48.6 % in the FDFG group and from 57.2 to 76.7 % in the FFG group during the observation period; however, there was no significant difference in the proportion of fatty tissue between these two groups. There were no significant differences between the average number of VEGF-positive cells in the FDFG group and the FFG group at POW1, 2, 4, 8, and 16. The average number of TUNEL-positive cells in the early period at POW1 was significantly lower in the FDFG group than in the FFG group., Conclusions: This rat model was useful for investigating the mechanisms of angiogenesis, apoptosis, structure maintenance, and fibromatous changes. From the present experimental study, we believe that FDFG is one of the most convenient materials currently available to repair small defects at the time of BCS even in the clinical field.

A 67-year-old man who was hospitalized at a mental hospital because of schizophrenia was admitted to our hospital with a complaint of dysphagia and vomiting. He was found to have advanced cancer in the middle thoracic esophagus. With the cooperation of a radiologist, a psychiatrist, and a nurse, we successfully performed chemoradiation therapy with S-1 and CDDP. The patient had adverse events of esophagitis and anuria during chemoradiation therapy. However, such adverse events were well controlled through the cooperation with a palliative care team and a urologist. Finally, we were able to enforce chemoradiation therapy with S-1 and CDDP without interruption.

Background: An association between inflammatory/immunonutritional status and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the utility of inflammatory/immunonutritional factors as therapeutic predictors for patients with locally advanced pancreatic cancer treated with chemoradiotherapy (CRT)., Methods: Ninety-six patients with histologically proven locally advanced pancreatic adenocarcinoma who underwent CRT were enrolled in this study. We evaluated significance of inflammation-based factors as predictors of therapeutic effect and prognosis., Results: The median progression free survival (PFS) and overall survival (OS) of all patients was 10 and 18 months, respectively. A Glasgow prognostic score (GPS) of 2 and plasma fibrinogen levels ≥ 400 mg/dL were independent predictors of poor PFS and OS. A prognostic nutritional index (PNI) ≥ 45 was a predictor of a significantly better reduction rate of the primary tumor. The prognosis between patients with GPS 0/1 and fibrinogen <400 mg/dL, GPS 2 or fibrinogen ≥400 mg/dL, and GPS 2 and fibrinogen ≥400 mg/dL were significantly different. Patients with GPS 2 and/or plasma fibrinogen ≥ 400 mg/dL had significantly higher incidence of metastasis within 6 months after CRT., Conclusions: GPS, fibrinogen, PNI are useful therapeutic and prognostic predictors in patients with locally advanced pancreatic cancer treated with CRT., (Copyright © 2015 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.)

Human leukocyte antigen (HLA)-F is one of the non-classical HLA class I molecules that protects the fetus in pregnancy. HLA-F expression was immunohistochemically examined and the association between clinical parameters and HLA-F expression was analyzed. Cancerous HLA-F and stromal HLA-F-positive infiltrating cells were detected in 91 (40.0%) and 186 (81.6%) cases, respectively. HLA-F positivity in cancer cells was significantly associated with tumor size (P < 0.05). There was a weak correlation between HLA-F positivity of cancer cells and HLA-F positive infiltrative cells (P < 0.01, r = 0.11). HLA-F positivity did not affect patients' survival in 209 breast cancer. However, confined to stage II breast cancer, the HLA-F positive group showed significantly poorer outcomes than the HLA-F negative group (P < 0.05). The present study provides the first evidence that HLA-F positivity in breast carcinoma affects clinicopathological factors and could be selected as a prognostic marker for limited clinical stage., (© 2015 The Authors. Pathology International published by Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Background: Esophageal squamous cell carcinoma is an aggressive gastrointestinal tract cancer. To date, the presence of circulating tumor cells (CTC) has been reported as a prognostic factor in peripheral blood from patients with gastrointestinal cancers., Methods: The CellSearch system was used to isolate and enumerate CTCs. A total of 90 patients with esophageal squamous cell carcinoma who received chemotherapy or chemoradiotherapy were enrolled. Peripheral blood specimens were collected before and after treatments., Results: At baseline analysis, CTCs were detected in 25 patients (27.8 %). Overall survival was significantly shorter in patients with than without CTCs. Follow-up blood specimens were obtained from 71 patients. Partial response, stable disease, and progressive disease after treatment were seen in 32, 12, and 27 patients, respectively. CTC positivity after treatment in the progressive disease group (40.7 %) was significantly higher than that of the partial response group (6.3 %). Patients with a change in CTC status from positive to negative had a good prognosis as well as patients without baseline CTCs., Conclusions: Evaluation of CTCs may be a promising indicator for predicting tumor prognosis and the clinical efficacy of chemotherapy or chemoradiation therapy in patients with esophageal squamous cell carcinoma.

A 66-year-old man was diagnosed with synchronous early esophageal cancer and advanced gastric cancer. He received CDDP-based combination chemotherapy (docetaxcel, CDDP, and TS-1). During chemotherapy for gastric cancer, he suddenly developed septic shock, requiring intensive treatment with antibiotics, intravenous immunoglobulin, circulatory and respiratory care, and hemoperfusion with a polymyxin B column. He also had disseminated intravascular coagulation (DIC), complicated by sepsis. Recombinant human soluble thrombomodulin (rTM) was administered to treat DIC. The intensive treatments described above allowed the patient to recover from septic shock and DIC several days later. Early and adequate treatment could be used to rescue a compromised cancer-bearing patient from septic shock following chemotherapy.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in gastrointestinal tract cancers and even patients with early ESCC have a high metastatic potential. Difficulties are associated with clinically predicting tumor progression and prognosis based on conventional tumor markers determined from preoperative blood examinations. The aim of the present study was to measure plasma fibrinogen levels and the neutrophil-lymphocyte ratio (NLR) in blood and compare the clinical impacts of their combined values (fibrinogen and neutrophil-lymphocyte ratio score-F-NLR score) and the modified Glasgow Prognostic Score (mGPS) in patients with ESCC.We classified 238 patients with ESCC based on cut-off values for hyperfibrinogenemia (>400 mg/dL) and high NLR (>3.0) as F-NLR scores of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), or 0 (neither abnormality). We also categorized patients based on cut-off values for high C-reactive protein (CRP) (>0.5 mg/dL) and hypoalbuminemia (<3.8 g/dL) as mGPS of 2 (elevated CRP and hypoalbuminemia), 1 (either elevated CRP or hypoalbuminemia), or 0 (neither elevated CRP nor hypoalbuminemia).The F-NLR score correlated with the depth of tumor invasion, lymph node metastasis, lymphovascular invasion, tumor size, and stage (all P < 0.05). Prognoses among the groups based on the F-NLR score and mGPS significantly differed (all P < 0.001). A multivariate analysis identified the depth of tumor invasion, lymph node metastasis, and F-NLR score as independent prognostic factors (P = 0.002, P = 0.007, and P = 0.037, respectively).The results of the present study showed that the F-NLR score is a promising blood predictor for tumor progression and outcomes in patients with ESCC.

A 68-year-old woman was diagnosed with advanced esophageal cancer with lymph node metastasis, for which she received neoadjuvant chemoradiotherapy. During therapy, she had loss of appetite and weight; therefore, we inserted a nasal feeding tube for her nutrition, after which, she gained weight soon. After therapy, she had a high fever with lymphocytopenia and was diagnosed with cytomegalovirus infection because of significantly high CMV antigenemia. Ganciclovir was administered immediately, and she recovered soon. Two months later, we performed esophagectomy, and she recovered without complications. Immediate diagnosis of CMV infection, ganciclovir administration, and nutrition through a feeding tube were useful for the esophageal cancer patient in this report who had immunosuppression and malnutrition during chemoradiation.

Purpose: Mediastinoscope-assisted transhiatal esophagectomy (MATHE) is a useful surgical procedure in esophageal cancer patients who have limited indications for transthoracic operations due to preoperative complications., Methods: In the last 10 years, 63 patients underwent MATHE at our department. We examined the clinical data of these patients and assessed the indications, postoperative outcomes, and prognostic factors of MATHE., Results: The 5-year overall survival (OS) rate was 53.4 %, and disease-free survival (DFS) rate was 66.0 %. Postoperative complications were observed in 22 cases (34.9 %), and recurrent disease occurred in 17 cases (27.0 %). On univariate analyses of OS, location of the tumor, tumor depth, lymph node metastasis, clinical stage, simultaneous resection of other organs, postoperative pneumonia, and blood loss were significant prognostic factors. On multivariate analyses, location of the tumor and lymph node metastasis were independent prognostic factors of OS. On univariate analyses, location of the tumor, tumor depth, lymph node metastasis, clinical stage, and blood loss were significant prognostic factors of DFS, while on multivariate analyses of DFS, lymph node metastasis and blood loss were independent prognostic factors., Conclusion: MATHE is a useful procedure for the middle to lower thoracic esophageal cancer patients without clinical lymph node metastasis with serious complications who were unable to undergo thoracotomy.

Background: We reported our experience of adenocarcinoma of sigmoid colon neovagina., Case Presentation: A 67-year-old female with a history of neovagina construction for Rokitansky syndrome complained of vaginal bleeding. She had a mucinous adenocarcinoma at the anterior aspect of the neovagina. Her original surgery, using sigmoid colon to construct the artificial vagina, was 40 years ago, Conclusions: This patient's case may contribute to our understanding of carcinogenesis in the colon.

Endoscopy is now being used for breast cancer surgery. Though it is used for mastectomy, lymph node dissection, and breast reconstruction, its prime use is for mastectomy. Because an incision can be placed inconspicuously in the axillary site, a relatively large incision can be created. A retractor with an endoscope, CO2, and an abrasion device with the endoscope are used for operation space security. It is extremely rare that an endoscope is used for lymph node dissection. For breast reconstruction, it may be used for latissimus muscle flap making, but an endoscope is rarely used for other reconstructions. Endoscopic mastectomy is limited to certain institutions and practiced hands, and it has not been significantly developed in breast cancer surgery. On the other hand, endoscopic surgery may be used widely in breast reconstruction. With respect to the spread of robotic surgery, many factors remain uncertain.

Background/aim: Interleukin-32 (IL32) has been newly-identified as a proinflammatory cytokine. In the present study, we aimed to clarify the clinical role of IL32-positive cells in esophageal squamous cell cancer (ESCC) and regulatory T-cell (Treg) infiltration in the stroma. A total of 179 patients with ESCC who underwent surgical resection from 1990 to 2004 were eligible for this study. The expression of IL32 and the degree of stromal infiltration by Tregs were examined simultaneously. The association between each factor and the clinicopathological features was analyzed. Sixty and 74 out of 179 patients with ESCC were regarded as having IL32-positive tumors and many Tregs (high-Treg group), respectively. The IL32-positive and high-Treg groups had significantly deeper tumor invasion than did the IL32-negative and low-Treg groups (p<0.05, for both groups). The multivariate analysis indicated that a combination of IL32 expression and presence of Tregs was one of the poor independent factors (p<0.05). IL32 expression and Treg infiltration in ESCC play an important synergistic role in tumor growth and invasion. The combination of IL32 positivity and degree of infiltration of Treg is a useful prognostic marker in ESCC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC). However, because some patients respond well to CRT and others do not, it is important to be able to predict response to CRT before beginning treatment by using markers. Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions in centrosome maturation and chromosome segregation. In this study, we investigated the relationship between the expression of Aurora-A and the response to CRT in patients with ESCC., Methods: We immunohistochemically investigated the expression of Aurora-A in biopsy specimens of untreated primary tumors of 78 patients with ESCC and determined the relationship between Aurora-A levels and patient responses to CRT, which consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation., Results: Tumors were judged as Aurora-A positive when more than 10% of the cancer cells displayed a distinct positive nuclear anti-Aurora-A immunoreaction by immunohistochemical evaluation. The tumors of 46 of 78 patients (58.9%) displayed positive expression of Aurora-A. In terms of clinical response the percentage of patients showing complete response (CR), incomplete response/stable disease of primary lesion (IR/SD), and progressive disease (PD) was 19.2, 69.2, and 11.5%, respectively. In terms of histological response the tumor grade of the 41 patients who underwent surgery was as follows: grade 1, 48.8%; grade 2, 29.2%; grade 3, 22.0%. CRT was effective for patients who had Aurora-A (+) tumors (clinically: P = 0.0003, histologically: P = 0.036)., Conclusions: Our results suggest that Aurora-A expression in biopsy specimens of primary tumors is associated with CRT efficacy in patients with ESCC. Assessment of Aurora-A expression in biopsy specimens maybe useful for regarding the potential utility of CRT therapy for patients with ESCC before treatment.

Human leukocyte antigen (HLA)-E and HLA-F are classified as non-classical HLA class Ib antigens. Ectopic HLA-E and HLA-F expression was recently detected in cancer cells; however, the clinical implication of their expression remains unknown. A total of 209 patients with gastric cancer were enrolled in this study. Immunohistochemistry was used to evaluate the expression of HLA-E and HLA-F in gastric cancer specimens. HLA-E and HLA-F expression were seen in the cell membrane. HLA-E and HLA-F expression significantly correlated with depth of invasion, nodal involvement, lymphatic invasion, and venous invasion. No significant correlation between HLA-E and HLA-F expression was found (p<0.05, r=0.24). The five-year survival rate of the HLA-E-positive group and HLA-F-positive group were significantly poorer than that of their respective negative groups. Combination of HLA-E and HLA-F made the p-value smaller than single analysis (p<0.009). This is the first report detailing a clinical implication of HLA-E and HLA-F expression simultaneously in gastric cancer. We identified that the HLA-E and HLA-F in gastric cancer independently affected clinical factors, including postoperative outcome. For HLA-E- or HLA-F-positive gastric cancer, we should settle on a treatment strategy that reinforces the host immune response., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A 48-year-old Japanese woman was found to have local recurrence of breast cancer in the chest wall following neoadjuvant chemotherapy, total mastectomy with axillary lymphadenectomy, postoperative radiation therapy to the chest wall, and adjuvant systemic therapy using trastuzumab. As a third line of treatment after recurrence, bevacizumab with paclitaxel was initiated for several metastatic lesions on the skin of the chest wall, left internal costal lymph nodes, and right axillary lymph nodes. The wound on the chest wall continued to expand in diameter and depth after the third course of bevacizumab with paclitaxel until the rib was exposed. After stopping the bevacizumab, granulation tissue expanded and by 3 months, had covered the bottom of the ulcer. The patient died soon thereafter, despite systemic chemotherapy with eribulin; however, there was no further bleeding from the ulcer on the chest wall or the exposed ribs.

Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function., Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome., Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007)., Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01273857., (© 2014 American Heart Association, Inc.)

Background: The transcription factor nuclear factor (erythroid-2)-related factor 2 (Nrf2) was originally identified as a critical regulator of intracellular anti-oxidants and of phase II detoxification enzymes through its transcriptional up-regulation of many anti-oxidant response element (ARE)-containing genes. Nrf2 protects not only normal cells but also cancer cells from cellular stress, and enhances cancer cell survival. Some studies have shown that Nrf2 expression in cancer patients has clinical significance. However, there has been no comprehensive analysis of the nuclear expression level of Nrf2 in gastrointestinal cancer cells. In this study we aimed to immunohistochemically evaluate the expression of Nrf2, and to assess its clinical significance in gastric cancer., Methods: A total of 175 gastric cancer patients who received R0 gastrectomy with standard lymph node dissection were enrolled. We immunohistochemically evaluated Nrf2 expression in the paraffin-embedded surgically resected specimens of these 175 patients. Group differences were analyzed using the χ (2) test, Fisher's exact test, and the Mann-Whitney U test. Associations between Nrf2 expression and clinicopathological features, including clinical outcome, were assessed using univariate and multivariate analyses, and Kaplan-Meier curves with the log-rank test, respectively., Results: Nrf2 immunoreactivity was predominantly identified in the nucleus of gastric cancer cells. Nrf2 positivity was closely associated with tumor size, tumor depth, lymph node metastases, lymphovascular invasion, histology and stage (p < 0.05 for all). A log-rank test indicated that the overall survival of the Nrf2-positive group was significantly poorer than that of the Nrf2-negative group (p < 0.01). And, positive Nrf2 expression was significantly associated with resistance to 5FU-based adjuvant chemotherapy (p = 0.024)., Conclusions: Nrf2 expression was positively associated with aggressive tumor behavior in gastric cancer. This result suggests that Nrf2 expression in gastric cancer is a potential indicator of worse prognosis.

Background/purpose: This study aimed to evaluate the feasibility and safety of a novel pancreaticogastrostomy technique for diminishing pancreatic fistulas after pancreaticoduodenectomy using gastric wrapping of the pancreatic stump with a twin square-shaped horizontal mattress and a suture fixing the main pancreatic duct to the gastric mucosa anastomosis [twin square wrapping (TSW) method]., Methods: Fifty-three patients undergoing pancreaticogastrostomy after pancreaticoduodenectomy were included in the study and chronologically divided into a conventional group (n = 32) and a TSW group (n = 21). The perioperative factors and the postoperative outcomes were retrospectively analyzed., Results: The operating time for the pancreatic anastomosis, the total operating time, and the blood loss volume in the TSW group were lower than in the conventional group, but without a statistically significant difference. The TSW group had a significantly lower postoperative white blood cell count and C-reactive protein level, with a reduced intra-abdominal fluid accumulation as assessed by computed tomography on postoperative day 7, had a lower incidence of postoperative complications and pancreatic fistulas, and achieved a shorter duration of drain placement and shorter postoperative hospital stays as compared to the conventional group., Conclusions: The TSW technique should be considered for reducing pancreatic fistulas by diminishing the postoperative inflammatory response and improving patient outcomes without increasing the operating time., (2015 S. Karger AG, Basel.)

Background: An appropriate timing for surgical resection of branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) to achieve sufficient postoperative survival is still unknown., Methods: Of 80 patients with histologically proven IPMNs, 61 patients who had BD-IPMN without pancreatic cancer concomitant with IPMN were enrolled in this study. We divided BD-IPMN into four groups according to disease progression: low to intermediate grade of dysplasia (LGD/IGD-IPMN), high grade of dysplasia (HGD-IPMN), minimally invasive IPMN (MI-IPMN: T1a), and invasive IPMN (IN-IPMN: ≥T1b). Indicators of surgical resection were investigated on the basis of pathological findings and postoperative prognosis., Results: Postoperative survival was distinctly worse for patients with IN-IPMN than for patients with MI-IPMN, HGD-IPMN, and LGD/IGD-IPMN. Postoperative disease-specific 5-year survival rate was 100 % in patients with IN-IPMN, HGD-IPMN, and LGD/IGD-IPMN, by contrast, 40 % in patients with IN-IPMN. The presence of two of the three factors (pancreatitis, serum carbohydrate antigen [CA] 19-9 levels >13 U/mL, and mural nodules) could distinguish HGD-IPMN from LGD/IGD-IPMN with a sensitivity of 92.9 %, specificity of 90.2 %, positive predictive value of 76.5 %, negative predictive value of 97.4 %, and accuracy of 90.9 %., Conclusions: To manage patients with BD-IPMN and achieve a good postoperative prognosis, surgical resection should be performed before progression to IN-IPMN.

Background: We have evaluated the safety and feasibility of combining median-to-lateral and anterior-to-median (MLAM) approaches to perform laparoscopic complete mesocolic excision (CME) with radical lymph node dissection along the gastrocolic trunk of Henle (GTH) for right hemicolon cancer., Patients and Methods: We retrospectively analyzed data obtained from a prospectively maintained database on 31 consecutive patients who had undergone laparoscopic CME with radical lymph node dissection for right hemicolon cancer between January 2010 and December 2013. We used video recordings of the procedure to assess the quality of the surgery and completeness of CME. We also assessed operative data, pathological findings, length of large bowel resected, complications, BMI, operative time by experience of surgeon, and length of hospital stay., Results: All patients had undergone en bloc resection of the enveloped parietal planes and radical lymph node dissection along the surgical trunk without any serious intraoperative complications. Twenty six and five patients graded mesocolic and intra-mesocolic plane, respectively. Five, three, eleven, and thirteen patients had T1, T2, T3, and T4 tumors, respectively. The median number of lymph nodes retrieved was 25, lymph node metastasis being identified in 11 patients. The mean length of large bowel resected was 21.8 cm. The mean operative time and intraoperative blood loss were 269 min and 39 mL, respectively. No intraoperative complications occurred in any patient. Three patients had postoperative complications. The mean BMI was 22.6 kg/m(2). The mean operative time for patients stratified by BMI of <22 or ≥22 was 225 and 297 min, respectively. There were no correlations with operative time by experience of surgeon. The median postoperative hospital stay was 13 days., Conclusions: Laparoscopic CME conducted by fusion fascia exposure with radical lymph node dissection along the GTH via a combination of MLAM approaches is a safe and feasible procedure for right hemicolon cancer.

Background: Perioperative staging laparoscopy is a useful tool for the detection of occult peritoneal metastases in gastrointestinal cancers. This retrospective study aimed to determine the clinical value of staging laparoscopy for advanced or recurrent gastric cancer., Methods: A total of 178 patients with advanced or recurred gastric cancer who underwent perioperative staging laparoscopy were enrolled. In the absence of peritoneal deposits (P1) and positive peritoneal cytology (CY1), gastrectomy with lymph node dissection was indicated with curative intent. If P1 or CY1 was detected intraoperatively, patients received intensive chemotherapy and laparoscopic surgical intervention., Results: Curative gastrectomy was performed in 104 patients after confirmation of P0 and CY0 status. P1 or CY1 was detected for the first time in 23 (15%) patients. A total of 13 patients were converted from gastrectomy to intensive chemotherapy after detection of P1 or CY1. Additional laparoscopic interventions included insertion of intraperitoneal reservoir port in 54 patients, insertion of a metallic stent in five, ileostomy for colon stricture in six, jejunostomy in 19, and gastrojejunostomy in 16. Of eight patients treated with intensive chemotherapy who underwent R0 gastrectomy after second-look laparoscopy, five are currently free from recurrence of gastric cancer for 25.5 months., Conclusions: Occult peritoneal dissemination was detected in about 14% in patients with tumors deeper than T2. Moreover, additional laparoscopic interventions can be utilized for P1 or CY1 patients. The excellent surgical outcomes of R0 gastrectomy after chemotherapy and second-look laparoscopy indicate that confirmation of P0 and CY0 status by staging laparoscopy is of value to determine treatment strategy in patients with advanced gastric cancer.