Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.

PURPOSE: Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). METHODS: A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. RESULTS: The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. CONCLUSIONS: The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. TRIAL REGISTRATION NUMBER: UMIN000026292.

Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract Cancers: The AMATERASU Randomized Clinical Trial.

Importance: Randomized clinical trials of vitamin D supplementation for secondary prevention in patients with cancer are needed, given positive results of observational studies. Objective: To determine whether postoperative vitamin D3 supplementation can improve survival of patients with digestive tract cancers overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels. Design, Setting, and Participants: The AMATERASU trial, a randomized, double-blind, placebo-controlled trial conducted at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. Patients aged 30 to 90 years with cancers of the digestive tract from the esophagus to the rectum, stages I to III, were recruited. Of 439 eligible patients, 15 declined and 7 were excluded after operation. Interventions: Patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/d; n = 251) or placebo (n = 166) from the first postoperative outpatient visit to until the end of the trial. Main Outcomes and Measures: The primary outcome was relapse-free survival time to relapse or death. The secondary outcome was overall survival time to death due to any cause. Subgroups analyzed had baseline serum 25(OH)D levels of 0 to less than 20 ng/mL, 20 to 40 ng/mL, and greater than 40 ng/mL; because of small sample size for the highest-baseline-level group, interactions were tested only between the low- and middle-baseline-level groups. Results: All 417 randomized patients (mean age, 66 years; male, 66%; esophageal cancer, 10%; gastric cancer, 42%; colorectal cancer, 48%) were included in the analyses. There was 99.8% follow-up over a median 3.5 (interquartile range, 2.3-5.3) years, with maximal follow-up of 7.6 years. Relapse or death occurred in 50 patients (20%) randomized to vitamin D and 43 patients (26%) randomized to placebo. Death occurred in 37 (15%) in the vitamin D group and 25 (15%) in the placebo group. The 5-year relapse-free survival was 77% with vitamin D vs 69% with placebo (hazard ratio [HR] for relapse or death, 0.76; 95% CI, 0.50-1.14; P = .18). The 5-year overall survival in the vitamin D vs placebo groups was 82% vs 81% (HR for death, 0.95; 95% CI, 0.57-1.57; P = .83). In the subgroup of patients with baseline serum 25(OH)D levels between 20 and 40 ng/mL, the 5-year relapse-free survival was 85% with vitamin D vs 71% with placebo (HR for relapse or death, 0.46; 95% CI, 0.24-0.86; P = .02; P = .04 for interaction). Fractures occurred in 3 patients (1.3%) in the vitamin D group and 5 (3.4%) in the placebo group. Urinary stones occurred in 2 patients (0.9%) in the vitamin D group and 0 in the placebo group. Conclusions and Relevance: Among patients with digestive tract cancer, vitamin D supplementation, compared with placebo, did not result in significant improvement in relapse-free survival at 5 years. Trial Registration: UMIN Identifier: UMIN000001977.

Prophylactic retention suture for surgical site infection: a retrospective cohort study.

BACKGROUND: Surgical site infection (SSI) is a common complication of gastrointestinal surgery. Because retention suture is known to prevent abdominal wound dehiscence, it is only considered indicated in high-risk patients. At present, there are no clear indications for retention suture. The purpose of this study was to analyze the effect of prophylactic retention suture and to determine what situations indicate prophylactic retention suture against SSI. MATERIAL AND METHODS: Between January 2014 and January 2016, 135 patients who underwent midline laparotomy in our hospital were analyzed. Inclusion criteria for this study were patients with American Society Anesthesiologists' physical status classification system (ASA-PS score) ≥ 3 or emergent surgery. RESULTS: Of the 135 patients, 30 (22.2%) received prophylactic retention suture. Diabetes mellitus, surgical wound classification, large incision, and retention suture were associated with SSI in multivariate analysis. In subgroup analysis, SSI risk factors were analyzed in each surgical wound classification. Only in surgical wound classification class II and III did retention suture significantly reduce the risk of SSI (odds ratio = 0.100 [0.012-0.837], P = 0.034). In class IV, however, half the patients developed SSI, regardless of retention suture. Table 3 summarizes the results of the subgroup analysis. CONCLUSIONS: The present data suggest that prophylactic retention suture reduces SSI for surgical wound classification class II or III. For class IV operations, however, other methods to prevent SSI are necessary.

Crus incision without repair is a risk factor for esophageal hiatal hernia after laparoscopic total gastrectomy: a retrospective cohort study.

BACKGROUND: Although postoperative esophageal hiatal hernia (EHH) is primarily considered a post-operative complication of esophagectomy, it is also a rare post-operative complication of laparoscopic total gastrectomy (LTG), with a reported incidence rate of 0.5 %. The purpose of this study is to analyze the incidence, clinical features, and prevention of EHH following LTG for gastric cancer. METHODS: Between October 2008 and July 2014, 78 patients who underwent LTG for gastric cancer in our hospital were analyzed. We compared the crus incision group (in which the left crus of the diaphragm was incised without suture repair) with the crus conserving or repair group (in which the crus was preserved or the crus was incised and underwent suture repair). The primary endpoint was incidence of postoperative EHH. RESULTS: Of the 78 patients, 7 (9.0 %) developed postoperative EHH. Three of seven patients (42.9 %) were symptomatic and required an emergency operation for intestinal obstruction. Four of seven patients (57.1 %) were asymptomatic and did not require an operation. Incising the left crus of the diaphragm without suture repair during LTG was considered the only risk factor for postoperative EHH (0 of 29 for preserving the crus or incising and performing suture repair of the crus vs. 7 of 49 in crus incision without suture repair; p = 0.033). CONCLUSIONS: The present data suggest that incision of the crus without suture repair is associated with EHH after LTG. If crus incision is required, crus repair may be effective for the prevention of postoperative EHH.

Breakthrough chemotherapy-induced nausea and vomiting: report of a nationwide survey by the CINV Study Group of Japan.

BACKGROUND: We conducted a nationwide survey on chemotherapy-induced nausea and vomiting (CINV) in Japan and demonstrated good compliance with Japanese CINV guidelines, resulting in good control of vomiting. However, almost half the patients experienced breakthrough CINV. We analyzed the survey results in relationship to the management of patients with breakthrough CINV. METHODS: This multicenter, prospective, observational study analyzed data for 1910 patients in Japan scheduled for moderately or highly emetogenic chemotherapy (MEC and HEC, respectively). Patients who developed CINV despite prophylactic use of antiemetics were administered rescue drugs. Patients who received cisplatin-based HEC (C-HEC), non-cisplatin-based HEC (N-HEC), or MEC were evaluated separately. RESULTS: A total of 989 patients experienced CINV, of whom 412 (44%) received rescue antiemetics during the study period. The rate at which patients with breakthrough CINV were started on rescue drugs ranged from 13% to 24%. Rescue drugs were given more frequently on days 2-4 for C-HEC and MEC and on days 1-2 for N-HEC. Eighty-six percent of patients received metoclopramide or domperidone. 5-HT3 receptor antagonists, antipsychotics, and anti-anxiety drugs were used for 11-5% of patients. The mean duration of antiemetic use was 2.6 days. CONCLUSIONS: Fewer than half of the patients with breakthrough CINV were treated with rescue antiemetics, suggesting that CINV was mild in the remaining patients. However, CINV was sufficiently severe to prevent eating in other patients, indicating the need for new drugs with different mechanisms to control CINV.

Randomized phase II study of daily and alternate-day administration of S-1 for advanced gastric cancer (JFMC43-1003).

PURPOSE: Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer. METHODS: 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m2/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate. RESULTS: The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15-2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97-2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007). CONCLUSION: The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.

Continuous Intraoperative Neuromonitoring Study Using Pigs for the Prevention of Mechanical Recurrent Laryngeal Nerve Injury in Esophageal Surgery.

PURPOSES: During esophageal surgery, clamping injury and injury associated with the use of energy devices are common mechanisms underlying intraoperative recurrent laryngeal nerve (RLN) damage. Recently, intraoperative neuromonitoring (IONM) has been applied to prevent RLN injury. This study was aimed at investigating the changes in the EMG signals associated with clamping injury of the RLN caused by picking up of the nerve with tweezers in domestic pigs. METHODS: Six domestic pigs (12 RLNs) underwent continuous IONM (CIONM) by our original automated periodic vagal nerve stimulation method. RESULTS: Our system can be used safely and accurately. The signals showed a decrease of the amplitude when the RLN was picked up and closed slowly by the double-action Maryland with jaw covers. If the clamp was released before the signal amplitude decreased to 50% of the baseline, the signal showed gradual recovery to the baseline in 12 ± 3 minutes. CONCLUSION: Although there were limitations in our study using domestic pig, including the small sample size, our results are expected to contribute to a decrease in the incidence of RLN damage during esophageal surgery.

Introduction of 2-octyl cyanoacrylate (Dermabond®) for incisional hernia mesh repair.

PURPOSE: We developed a new technique, sutureless mesh fixation, using 2-octyl cyanoacrylate (Dermabond®, a surgical tissue adhesive) for incisional hernia repair. The objective of this article is to introduce the new technique and to examine whether the technique provides sufficient resistance to abdominal pressure. METHODS: We conducted two tests using a porcine model, a traction experiment and artificial pneumoperitoneum test. In the traction experiment, the adherence properties of Dermabond® with mesh and peritoneum were examined using a tissue fragment from a pig. In the artificial pneumoperitoneum test, which used an incisional hernia porcine model, mesh was implanted on the peritoneum in the abdominal cavity with Dermabond®. It was then determined whether sutureless mesh fixation could bear artificial abdominal air pressure. RESULTS: In the traction experiment, Dermabond®, which bonded the mesh to the peritoneum, tolerated pressure up to 2.45 × 103 mmHg. In the artificial pneumoperitoneum test, the mesh was strongly fastened to the peritoneum by means of only Dermabond®, and there was little air circulation even without closing the wound over the mesh. CONCLUSIONS: Sutureless mesh fixation with Dermabond® is technically feasible and promises to provide sufficient resistance to abdominal pressure.

Testing the effectiveness of antiemetic guidelines: results of a prospective registry by the CINV Study Group of Japan.

BACKGROUND: Many cancer patients suffer from the common side effect of chemotherapy-induced nausea and vomiting (CINV). Guidelines recommend a combination of two prophylactic antiemetics for moderately emetogenic chemotherapy (MEC) and three for highly emetogenic chemotherapy (HEC) and certain MEC regimens. METHODS: This multicenter, prospective, observational study analyzed data for 1,910 patients in Japan scheduled for MEC or HEC. Use of antiemetic prophylaxis in relation to type of chemotherapy, incidences of and risk factors for nausea, vomiting, and acute versus delayed CINV, and estimated incidence of CINV by staff were analyzed using Fisher's exact test and multivariate logistic regression. The patients recorded the incidence of CINV and severity of nausea by visual analogue scales daily for 7 days after receiving chemotherapy. RESULTS: A total of 240 (20.1 %) HEC and 476 MEC patients (66.6 %) received 2 antiemetics, compared with 883 (73.9 %) and 200 (28.0 %), respectively, who received 3 antiemetics. Approximately 74 % of HEC and 95 % of MEC patients received antiemetic therapy in compliance with guidelines. Acute nausea and vomiting were well controlled, but high incidences of delayed nausea occurred in both HEC and MEC patients. Delayed vomiting (p < 0.0001) was significantly less frequent in patients receiving three compared with 2 antiemetics. Female sex was a major risk factor for CINV. Medical staff tended to overestimate the incidence of CINV. Among HEC regimens, the incidence of CINV and the degree of nausea on day 1 of anthracycline-cyclophosphamide combination therapy were higher than with a cisplatin-based regimen. CONCLUSIONS: Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed nausea in HEC and MEC patients. Identification of individual risk factors, such as female sex, will assist in the development of personalized treatments for CINV. More intensive antiemetic therapy or a different modality of prophylaxis should be considered for the control of acute CINV in an anthracycline-cyclophosphamide regimen.

Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001).

BACKGROUND: This multi-center, phase III trial assesses the efficacy of daikenchuto (TU-100) on gastrointestinal disorders after hepatic resection (UMIN Registration No. 000003103). MATERIALS AND METHODS: A total of 231 patients, who underwent hepatic resection at 26 Japanese centers, were enrolled. Patients were randomly assigned to receive either oral doses (15 g/day, three times a day) of TU-100 or placebo control from preoperative day 3 to postoperative day 10, except on the day of surgery. Primary end points were the time from extubation until the first postoperative bowel movement (FBM-T), serum C-reactive protein (CRP) and ammonia levels. RESULTS: Finally, 209 patients (TU-100: n = 108, placebo: n = 101) were included in the statistical analysis. The median FBM-T was 88.2 h (95 % CI 74.0-94.1) in the TU-100 group and 93.1 h (95 % CI 83.3-99.4) in the placebo group, demonstrating that TU-100 accelerated the time to first bowel movement significantly more than placebo control. Serum CRP levels did not differ significantly during the study period, although serum CRP levels in the TU-100 group tended to be lower than those in the placebo group in patients with grade B liver damage. Meanwhile, the two groups had similar serum ammonia levels. TU-100-related serious adverse events did not occur during the study. CONCLUSIONS: TU-100 appears to improve gastrointestinal dysmotility and reduce serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer.

Undervalued criteria in the evaluation of multimodal trials for upper GI cancers.

Global economies and their health systems face a huge challenge from cancer: 1 in 3 women and 1 in 2 men will develop cancer in their lifetime. In the less developed countries, the volume of cancer patients will overwhelm the existing healthcare systems. Even in developed regions, patients with upper gastrointestinal (GI) cancer usually present with locally advanced tumors that their prognosis is poor. A detailed knowledge of anatomy, embryology, epidemiology, tumor classifications and tumor growth is key understanding and evaluating the relevant research. We review undervalued criteria necessary to evaluate the response to multimodal therapy for upper GI cancers.

Initial clinical trial of a novel hemostat, TDM-621, in the endoscopic treatments of the gastric tumors.

BACKGROUND AND AIM: The feasibility of TDM-621, the synthetic infectious agent-free peptides, was tested in hemostasis of the bleeding after endoscopic treatments of the gastric tumors. METHODS: The patients who underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) were enrolled in the present study. The subject of hemostasis was the oozing after the EMR or ESD. The hemostatic effect, the secondary hemorrhage from one postoperative day to the day before discharge and operability were studied. RESULTS: The hemostatic effects were assessed in 12 patients. It was "remarkably effective" in 11 patients and "effective" in 1 patient. The operability was "very easy" in two patients, "easy" in eight patients and "acceptable" in two patients. No secondary hemorrhage was observed in all of 12 patients. No adverse effect considered to be related to TDM-621 was observed. CONCLUSION: It was shown that hemostasis using TDM-621 was feasible after endoscopic treatments of the gastric tumors without any technical trouble or adverse event.

Successful treatment of non-occlusive mesenteric ischemia (NOMI) using the HyperEye Medical System™ for intraoperative visualization of the mesenteric and bowel circulation: report of a case.

Non-occlusive mesenteric ischemia (NOMI), leading to intestinal gangrene without a demonstrable occlusion in the mesenteric artery, is a rare condition with extremely high mortality. We report a case of NOMI diagnosed preoperatively by computed tomography and treated successfully with surgery, assisted by indocyanine green (ICG) fluorescence in the HyperEye Medical System (HEMS), a new device that can simultaneously detect color and near-infrared rays under room light. This allowed for precise intraoperative evaluation of the mesenteric and bowel circulation. Although the necrotic bowel wall of the distal ileum and the segmental ischemia of the jejunum were visible, the jejunum was finally preserved because perfusion of ICG fluorescence was confirmed. The patient, an 84-year-old man, had an uneventful postoperative course and is alive without critical illness 8 months after surgery. We report this case to demonstrate the potential effectiveness of HEMS during surgery for NOMI.

Modified gastroduodenostomy in laparoscopy-assisted distal gastrectomy: a 'tornado' anastomosis.

BACKGROUND/AIMS: This study was to examine the utility of a modified double-stapling end-to-end gastroduodenostomy method ('Tornado' anastomosis) compared to a method with an additional gastrotomy ('Anterior Incision' method) in laparoscopy-assisted distal gastrectomy. METHODOLOGY: Forty-two patients with gastric cancer who underwent laparoscopy-assisted distal gastrectomy were analyzed retrospectively. Billroth-I using an additional gastrotomy was performed in 24 patients (AI group) and Billroth-I without an additional gastrotomy was performed in 18 (TOR group). Clinicopathological features, operative outcomes (lymph node dissection, operative time, operative blood loss) and postoperative outcomes (complications, postoperative hospital stay, and body weight loss at one year after surgery) were evaluated and compared between groups. RESULTS: Operative time was significantly shorter in the TOR group (251 min) than in the AI group (282 min) (p < 0.01). There were no statistically significant differences in operative blood loss, postoperative complications, and hospital stay between the 2 study groups. Body weight loss at one year after surgery was -5.8 kg in the TOR group and -6.5 kg in the AI group, without a statistically significant difference. CONCLUSIONS: Completion time for Billroth-I anastomosis was significantly shorter with Tornado anastomosis than with the Anterior Incision method, with safety equal between the two methods.

Surgical therapy and chemoradiotherapy for postoperative recurrent esophageal cancer.

BACKGROUND/AIMS: A retrospective analysis of therapeutic modalities used in postoperative recurrent esophageal cancer. METHODOLOGY: Among 43 esophageal cancer patients who underwent esophagectomy between 2003 and 2010, recurrence was found in 15. Best supportive care was given to two patients and another patient was referred to another hospital. The remaining 12 patients were treated by the following modalities: Surgical resection: 2 cases; chemoradiotherapy: 7 cases; chemotherapy: 2 cases; and radiotherapy: 1 case. The median survival time, 1-year survival rates, and response rates were examined. Data from 13 esophageal cancer patients who underwent chemoradiotheray as an initial therapy in the same period were collected and compared with recurrent cases treated with chemoradiotherapy. RESULTS: For all 12 patients, the median overall survival time was 19.5 months, and the 1-year survival rate was 83%. Among 7 chemoradiotherapy patients, the response rate was 57%. The median survival time was 23 months, and the 1-year survival rate was 86%. The response rate of 13 patients receiving chemoradiotherapy as an initial therapy was 69%. The median overall survival time was 12 months and the 1-year survival rate was 54%. CONCLUSIONS: Re-operation and chemoradiotherapy for recurrent esophageal cancer might be as effective as the same treatment used initially.

Application of the HyperEye Medical System for esophageal cancer surgery: a preliminary report.

The HyperEye Medical System is a newly developed device that allows for the visualization of the fluorescent image of indocyanine green enhanced by near-infrared light among the surrounding vivid color images. We recently applied this system to confirm the blood flow of an esophageal substitute, and for sentinel node navigation during esophagectomy. Five consecutive patients with thoracic esophageal cancer who underwent a subtotal esophagectomy between June 2010 and May 2011 were enrolled in the study. The esophageal substitute used for reconstruction was the stomach and ileocecum in four and one cases, respectively. In all cases with a reconstructive stomach, fine arterial blood flow and venous perfusion were observed. The blood flow of the reconstructive colon was poor before microvascular anastomosis, however, it dramatically increased after anastomosis. Concerning the sentinel node navigation, the fluorescence of lymph nodes, lymphatic vessels, and the tumor site were detected. The postoperative courses of all cases were uneventful, with no mortalities or anastomotic leakage occurring.

Direct inhibition of the transforming growth factor-ß pathway by protein-bound polysaccharide through inactivation of Smad2 signaling.

Transforming growth factor-ß (TGF-ß) is involved in the regulation of cell proliferation, differentiation, and apoptosis and is associated with epithelial-mesenchymal transition (EMT). Inhibition of the TGF-ß pathway is an attractive strategy for the treatment of cancer. We recently screened for novel TGF-ß inhibitors among commercially available drugs and identified protein-bound polysaccharide (PSK) as a strong inhibitor of the TGF-ß-induced reporter activity of 3TP-lux, a TGF-ß1-responsive luciferase reporter. Protein-bound polysaccharide is used as a non-specific immunostimulant for the treatment of gastric and colorectal cancers in Japan. The anticancer activity of this agent may involve direct regulation of growth factor production and enzyme activity in tumors in addition to its immunomodulatory effect. Although several clinical studies have shown the beneficial therapeutic effects of PSK on various types of tumors, its mechanism of action is not clear. In the present study, Western blot analysis showed that PSK suppressed the phosphorylation and nuclear localization of the Smad2 protein, thereby suggesting that PSK inhibits the Smad and MAPK pathways. Quantitative PCR analysis showed that PSK decreased the expression of several TGF-ß pathway target genes. E-cadherin and vimentin immunohistochemistry showed that PSK suppressed TGF-ß1-induced EMT, and FACS analysis showed that PSK inhibited the EMT-mediated generation of CD44(+) /CD24(-) cells. These data provide new insights into the mechanisms mediating the TGF-ß-inhibiting activity of PSK and suggest that PSK can effectively treat diseases associated with TGF-ß signaling.

Molecular detection of sentinel node micrometastases in patients with clinical N0 gastric carcinoma with real-time multiplex reverse transcription-polymerase chain reaction assay.

PURPOSE: Described is a novel real-time multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay suitable for intraoperative detection of micrometastasis (MM) in sentinel nodes (SNs) dissected from patients with clinical N0 (cN0) gastric carcinoma. METHODS: One hundred three patients with gastric cancer, who were preoperatively diagnosed with cN0 and clinical T1 or T2, were enrolled. The patients underwent SN mapping followed by standard radical gastrectomy with lymph node dissection. In addition to all SNs, non-SNs (NSNs) within the SN lymphatic basin and NSN from a different lymphatic basin were randomly sampled. All SNs and NSNs were examined by routine histologic diagnosis and RT-PCR for the expression of cytokeratin (CK) 19, CK20, and carcinoembryonic antigen (CEA). RESULTS: The RT-PCR assay and histologic examination were performed in 512 SNs and 299 NSNs from 103 patients. Pathologic l lymph node metastasis was revealed in 13 (12.6%) of 103 patients. All metastatic lymph nodes were identified within SNs. SNs of these 13 patients had positive findings on RT-PCR. Twenty-eight (27.2%) of 103 patients had negative histopathology but positive findings on RT-PCR. In 7 patients (6.8%), SNs were negative but NSNs were positive on RT-PCR. RT-PCR-positive NSNs were present in the same station as corresponding SNs in 3 of these 7 patients and in the same basin as SNs in 4 patients. CONCLUSIONS: The real-time multiplex RT-PCR assay is a useful tool for the detection of MM in SNs and NSNs in patients with gastric cancer.

Role of high mobility group box chromosomal protein 1 in ischemia-reperfusion injury in the rat small intestine.

BACKGROUND: High mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxic shock and sepsis. The purpose of the present study was to investigate the role of HMGB1 in response to ischemia-reperfusion injury. METHODS: Ischemia-reperfusion injury was induced in male Wistar rats by clamping the superior mesenteric artery for 60 min. Using this model, the serum concentrations and localization of HMGB1 were investigated. The histologic findings from reperfused intestines and the survival rates were compared between the anti-HMGB1 antibody treatment groups (group A treated with 6.0 mg/kg antibody and group B with 0.6 mg/kg antibody) and the control antibody treatment group (control group). RESULTS: Serum HMGB1 concentrations increased early after reperfusion and peaked at 3 h. Immunohistochemistry for HMGB1 revealed a high degree of positive staining in the epithelial cells of the damaged villi. Anti-HMGB1 antibody treatment significantly reduced this damage (P < 0.05) and improved the 48-h survival rate (90% in group A versus 50% in the controls; P < 0.05). CONCLUSIONS: These results suggest that HMGB1 plays a key role in small intestinal ischemia-reperfusion injury.

Steroid-free living donor liver transplantation for HCV--a multicenter prospective cohort study in Japan.

This prospective, non-randomized, multicenter cohort study analyzed the safety and efficacy of a steroid-free immunosuppressive (IS) protocol for hepatitis C virus (HCV)-positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assigned the steroid-free IS protocol (Fr group) and 29 the traditional steroid-containing IS protocol (St group). Serum HCV RNA levels increased over time and were higher in the St group until postoperative day 90 (POD 14, p=0.013). Preemptive anti-HCV therapy was started in a higher percentage of recipients (59.3%) in the Fr group than in the St group (31.0%, p=0.031), mainly due to early HCV recurrence. The incidence of HCV recurrence at one yr was lower in the Fr group (22.2%) than in the St group (41.4%; p=0.066). The incidence of acute cellular rejection was similar between groups. New onset diabetes after transplant, cytomegalovirus infection, and renal dysfunction were significantly less frequent in the Fr group than in the St group (p=0.022, p<0.0001, p=0.012, respectively). The steroid-free IS protocol safely reduced postoperative morbidity and effectively suppressed both the HCV viral load in the early post-transplant period and HCV recurrence in HCV-positive LDLT recipients.