Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Prospective observational study of the efficacy of oral uracil and tegafur plus leucovorin for stage II colon cancer with risk factors for recurrence using propensity score matching (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors. METHODS: We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm. RESULTS: Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW. CONCLUSIONS: Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012).

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.

[Effectiveness of indocyanine green fluorescence in endoscopic marking in gastric cancer surgery:a feasibility study for replacing India ink].

When injected, indocyanine green (ICG) immediately combines with lipoproteins to fluoresce. Here, we studied whether ICG fluorescence is effective for endoscopic marking in gastric cancer surgery using a photodynamic eye (PDE) camera and fluorescent endoscope. An ICG solution was endoscopically injected into the submucosal layer of the gastric tumor 3 days before surgery. We observed the lesions using both a PDE camera and a fluorescent endoscope during laparotomy and laparoscopy, respectively;we also observed the fluorescent luminance and fluorescent size of the resected lesions. We could intraoperatively detect the size of the resected lesions in eight patients with early gastric cancer and six patients with advanced gastric cancer. We believe that the use of ICG fluorescence in endoscopic marking requires additional information, such as the volume of the ICG solution and the timing of the ICG injection.

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function.

BACKGROUND: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. MATERIALS AND METHODS: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. RESULTS: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. CONCLUSION: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

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.

Macro- and microscopic findings of ICG fluorescence in liver tumors.

BACKGROUND: Reports detailing microscopic observations of indocyanine green (ICG) fluorescence imaging (IFI) in hepatocellular carcinoma (HCC) and metastatic liver cancer are rare. We were able to perform macro- and microscopic IFI results in postoperative paraffin-embedded tissue samples and formalin-fixed specimens from liver tumors. METHODS: Between April 2010 and March 2014, 19 patients with HCC or liver metastases of colorectal tumors underwent liver resection. ICG solution was injected into the peripheral vein from 14 to 2 days prior to operation. We observed liver tumor IFI during the laparotomy and IFI in resected liver sections using a photo dynamic emission (PDE) camera. The IFI of paraffin-embedded tissue samples was observed using a charge-coupled device (CCD) camera. Moreover, we microscopically performed tissue section IFI using a fluorescence microscope with an ICG-B-NQF. RESULTS: We performed that IFI characteristics depended on tumor type macroscopically and microscopically. In normal liver tissue, fluorescence consistent with the bile canaliculus was observed. HCC had heterogeneous IFI, forming a total or partial tumor and rim pattern. In metastatic carcinoma, we performed that non-tumor cells in the marginal region showed fluorescence and tumor cells in the central region did not fluoresce. CONCLUSIONS: We confirmed that the variations of ICG fluorescence imaging patterns reflect different tumor characteristics in not only macroscopic imaging as previous reports but also microscopic imaging. Moreover, the ICG fluorescence method is useful for postoperative pathological detection of microscopic lesions in histopathological specimens. ICG fluorescence in paraffin-embedded tissue samples and formalin-fixed specimens is preserved in the long term.

Navigation using indocyanine green fluorescence imaging for hepatoblastoma pulmonary metastases surgery.

To achieve precise and sensitive detection of chemotherapy-resistant hepatoblastoma pulmonary metastases, we performed surgery using indocyanine green (ICG) fluorescence imaging navigation. Lung metastasectomies were performed in 10 patients aged from 1 to 11 years. ICG (0.5 mg/kg) was injected intravenously 24 h before the operation. After a thoracotomy had been performed, a 760-nm infrared ray was applied to the lung using a generator and the 830-nm evoked fluorescence was collected and visualized on a real-time display. In total, 250 fluorescence-positive lesions were extirpated in 37 operations. All of the pathologically positive lesions were clearly fluorescence positive. The diameter of the smallest detectable lesion was 0.062 mm. In two patients, there were 29 extirpated lesions that were pathologically proven not to be hepatoblastoma metastases. Although a problem of false positive remains, this method is very useful for the detection of small pulmonary metastases.

[Distal gastrectomy for initially unresectable gastric cancer with pyloric stenosis following gastrojejunostomy and S-1 plus CDDP chemotherapy].

We report a case of advanced gastric cancer with pyloric stenosis, in which a curative resection was performed following gastrojejunostomy and S-1 based chemotherapy. A 46-year-old female presenting with vomiting was diagnosed with unresectable gastric cancer with pyloric stenosis after a detailed examination. She underwent laparotomy, which revealed a T4 tumor invading the pancreas head and involving the gallbladder. A gastrojejunostomy was performed. After the operation, chemotherapy of S-1(100mg/body, days 1-21)plus cisplatin(85mg/body, day 8)was administered. After 4 courses, the tumor size was markedly reduced upon imaging examinations. Six months after gastrojejunostomy, distal gastrectomy was curatively performed. The pathological findings were type 3, por1, pT4a(SE), pN1, M0, pStage III A. After 5 courses of S-1(100mg/day, days 1-28)as adjuvant chemotherapy, she had a recurrence at a lymph node behind the pancreas head. Despite irinotecan+cisplatin following docetaxel therapy, she had no effective benefits and died from the cancer 17 months after the first operation. The prognosis of unresectable gastric cancer with pyloric stenosis is not promising; however, gastrojejunostomy following S-1-based chemotherapy could lead such patients to curative resection and a longer survival time.

Sentinel node mapping guided by indocyanine green fluorescence imaging during laparoscopic surgery in gastric cancer.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging has recently been reported as a new method for sentinel node (SN) mapping in several types of cancers. In this study, we determined the possible usefulness of SN mapping guided by ICG fluorescence imaging during laparoscopy-assisted gastrectomy (LAG) for gastric cancer. METHODS: Our series consisted of 77 patients with cT1- or cT2-stage gastric cancer who had undergone LAG (LAG group; 38 patients) or conventional open gastrectomy (OG group; 39 patients). Intraoperative SN mapping guided by ICG fluorescence imaging was conducted with a charge-coupled device camera with a light-emitting diode as the light source and a cut filter as the detector. RESULTS: The detection rate and mean number of fluorescent nodes (FNs) were 94.7% and 7.9, respectively, in the LAG group, and 94.9% and 7.2, respectively, in the OG group. The accuracy and false-negative rates were 97.2% (35 of 36 cases) and 25% (1 of 4), respectively, in the LAG group, and 91.9% (34 of 37) and 23.1% (3 of 13), respectively, in the OG group. Among 33 LAG group patients and 27 OG group patients without FN metastasis, lymph node metastasis was found only in non-SNs located in the same lymphatic basin as the detected FNs. CONCLUSIONS: SN mapping guidance by ICG fluorescence imaging could be useful for predicting the lymph node metastasis in gastric cancer, even during LAG. Our data suggest that dissection of the lymphatic basin containing FNs with laparoscopic surgery may be a promising approach as a new type of minimally invasive surgery for patients with cT1- or cT2-stage gastric cancer having no metastasis in FNs.

Health-related quality of life in patients with advanced colorectal cancer: results from a phase II study of S-1 combined with irinotecan (CPT-11).

BACKGROUND: We carried out this study to examine the health-related quality of life (HRQOL) of patients with advanced colorectal cancer treated with the oral fluoropyrimidine S-1 plus irinotecan (CPT-11). METHODS: HRQOL was assessed at baseline (pretreatment) and at 5-week intervals during treatment, using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires. The HRQOL data for 12 preselected scales and 21 courses of treatment were then analyzed longitudinally. RESULTS: Thirty-seven patients completed the baseline and post-treatment HRQOL assessments. Statistically significant differences between the baseline and post-treatment HRQOL scores were observed for the global QOL, social function, and pain scales (all QLQ-C30), as well as the body image, future perspective, gastrointestinal tract symptoms, weight loss, and chemotherapy side effects scales (all QLQ-CR38); favorable post-treatment results were observed for all the scales except for body image and chemotherapy side effects, for which post-treatment deteriorations were observed. The changes in body image, future perspective, weight loss, and chemotherapy side effects were each greater than ten points and seemed clinically significant. CONCLUSION: Combined treatment with S-1 plus CPT-11 resulted in an acceptable deterioration in HRQOL functioning and symptoms, compared with baseline levels.

[A case of primary gastric choriocarcinoma treated by curative operation after neoadjuvant chemotherapy with S-1/CDDP].

We experienced a case of primary gastric choriocarcinoma(PGC)treated by curative operation after neoadjuvant chemotherapy with S-1/CDDP. Gastric endoscopy was carried out on this 43-year-old woman with epigastric discomfort and revealed an ulcerative lesion in her stomach. Choriocarcinoma in the gastric lesion was pathologically shown by endoscopic biopsy, so we diagnosed the patient without another primary lesion as PGC. The patient was initially treated by five courses of neoadjuvant chemotherapy with S-1/CDDP due to the metastases of Virchow and intraabdominal lymph nodes, and then a curative operation could be performed because of disappearance of the lymph node metastases by neoadjuvant chemotherapy. The patient was continuously treated by S-1 after gastrectomy but was dead due to the multiple metastases of the liver and adrenals, and the multiple recurrences of lymph nodes four months after the surgery. Further therapeutic strategy by chemotherapies against PGC is needed to ameliorate the prognosis.

Sentinel node mapping guided by indocyanine green fluorescence imaging in gastric cancer.

OBJECTIVE: In this study, we determined the possible usefulness of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in the management of gastric cancer. SUMMARY BACKGROUND DATA: ICG fluorescence imaging system has recently been developed for obtaining biochemical information from living tissues. METHODS: Our series consisted of 56 patients with gastric cancer who underwent standard gastrectomy with lymphadenectomy. Two milliliters of ICG solution (0.5%) was injected into the submucosa around the tumor endoscopically before the operation or into the subserosa intraoperatively. ICG fluorescence imaging was conducted using a charge-coupled device camera with a light-emitting diode having a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. RESULTS: SNs were detected in 54 (96.4%) of the 56 patients, and the mean number of SNs was 7.2 +/- 7.0. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. cT1-stage cancers were associated with a significantly higher accuracy rate (97.2% vs. 72.2%, P = 0.0127) than cT2-or cT3-stage cancers. Preoperative ICG injection was associated with a significantly higher incidence of cT1-stage cancers (87.1% vs. 40.0%, P = 0.0004), a larger mean number of SNs (9.9 +/- 7.5 vs. 4.1 +/- 5.0, P < 0.0001), a higher accuracy rate (100% vs. 73.9%, P = 0.0039), and a lower false negative rate (0% vs. 60.0%, P = 0.0345) as compared with intraoperative ICG injection. CONCLUSIONS: This study shows that ICG fluorescence imaging allows highly sensitive image-guided intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN mapping guided by ICG fluorescence imaging might be useful for predicting the metastatic status in lymph nodes in cases of gastric cancer, especially those with cT1-stage cancer.

Prospective randomized trial for determination of optimum size of side limb in low anterior resection with side-to-end anastomosis for rectal carcinoma.

PURPOSE: Functional outcome after low anterior resection with side-to-end anastomosis is comparable with that after a colonic J-pouch construction. The optimum size of the side limb has yet to be determined. This prospective randomized trial compared a 3-cm (short) and 6-cm (long) side limb. METHODS: Forty-four patients with a mid or low rectal cancer undergoing low anterior resection were randomly assigned to each group. Physiologic and clinical assessments were performed preoperatively and at 3, 6, and 12 months after ileostomy closure. Defecography was performed at six months after ileostomy closure. RESULTS: Twenty patients in each group completed the study. Among them, one patient with a short limb and two others with a long limb developed leakage. Sphincter function and reservoir function were similar between the groups. Bowel function or incontinence scoring was similar between the groups. The incidence of incomplete evacuation assessed by defecography in the long limb group was significantly greater than in the short limb group (13/20 long and 5/20 short, P = 0.025). One patient in the long limb group experienced fecal impaction. CONCLUSION: The study showed similar clinical results in patients with either a short limb or a long limb but seemed to be underpowered. A long limb may be associated with fecal impaction in patients undergoing low anterior resection with side-to-end anastomosis.

Cold preservation of the liver with oxygenation by a two-layer method.

BACKGROUND: The two-layer method (TLM) has recently been found to be superior to simple cold storage in University of Wisconsin (UW) solution as a means of pancreas preservation for islet transplantation. In this study, we investigated whether TLM would result in better hepatocyte function over UW cold storage and if it could be applied to hepatocyte transplantation. MATERIALS AND METHODS: Hepatocytes from male Sprague Dawley rat livers were isolated and divided into three groups: a non-preservation group (group 1), a 10-h preservation group (group 2), and a 24-h preservation group (group 3). Groups 2 and 3 were then divided into three subgroups: a group preserved by the TLM (subgroup a), a group preserved in UW solution (subgroup b), and a group preserved in water (subgroup c). Isolated hepatocytes were evaluated for cell yield, viability, and adenosine triphosphate level after preservation. Hepatocytes were either cultured or transplanted. RESULTS: Although no differences in cell yield or morphological findings were observed between any of the groups, TLM significantly improved hepatocyte viability and adenosine triphosphate levels in comparison with UW cold storage. Albumin production or urea synthesis were significantly higher in subgroup 3a than in subgroup 3b at almost all time points. Surprisingly, after hepatocyte transplantation, the serum albumin level in subgroup 2a was significantly higher than in subgroup 2b at every time point. CONCLUSIONS: The results of this study demonstrated that liver preservation by the TLM before hepatocyte isolation might be beneficial and will be useful in the field of hepatotocyte transplantation.

Colonic tattooing using fluorescence imaging with light-emitting diode-activated indocyanine green: a feasibility study.

PURPOSE: We investigated the feasibility of a fluorescence imaging technique using light-emitting diode (LED)-activated indocyanine green (ICG) fluorescence. METHODS: Indocyanine green injections were given to patients undergoing preoperative colonoscopy for early colon cancer or colon adenoma. During subsequent laparotomy, the colon was first observed with the naked eye, and then using a prototype machine with a charge-coupled device (CCD) video camera equipped with a cutoff filter and a LED at a wavelength of 760 nm as the light source. RESULTS: LED-induced fluorescence showed tumor localization clearly and accurately in all ten patients (100%) enrolled in this study, whereas it was seen with the naked eye as a green spot in only two patients (20%) (P = 0.0077; Wilcoxon's signed-rank test). There were no complications of LED-induced fluorescence and no inflammatory signs were noted on the hematoxylin-eosin-stained slides for the identified injection sites in the resected specimens. CONCLUSIONS: Colonic tattooing using this fluorescence imaging technique of LED-activated ICG fluorescence is a new concept of colonic marking based on the characteristics that ICG is a near infrared fluorescent dye, and is useful, without any adverse effects, to identify perioperatively the tumor localization.

[Evaluation of 5-fluorouracil-related genes in breast cancer to predict the effect of adjuvant therapy with CMF].

The correlations between mRNA expressions of 5-fluorouracil(5-FU)-related enzymes; thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), thymidine phosphorylase(TP), and orotate phosphoribosyltransferase (OPRT)in breast cancers, along with disease-free survival(DFS), were investigated in 35 patients treated with postoperative adjuvant chemotherapy using cyclophosphamide, methotrexate and 5-fluorouracil(CMF). The patients treated with CMF were divided into two groups, a lower group(L group)and a higher group(H group), according to the median value of the mRNA expression for each enzyme in 220 breast cancer specimens, which were resected between 1996 and 1998 in our institute. 5-year DFS was not significantly different between TS-L and H group(60% and 80%, p=0.38), DPD-L and H group(57.9% and 86.7%, p=0.088), and TP-L and H group(70% and 73.3%, p=0.89), respectively. 5-year DFS in the OPRT-H group(88.9%)was significantly better than that in the OPRT-L group(50%) (p=0.024). In the OPRT-H group, despite the fact that the proportion of patients with lymph node involvement in the CMF group was significantly higher than that in the postoperative adjuvant hormone therapy group, 5-year DFS was not significantly different between the two groups(p=0.10). Our results suggest that OPRT level was the significant predictive marker for DFS in the breast cancer patients treated with postoperative adjuvant chemotherapy using CMF.

Effect of mosapride on recovery of intestinal motility after hand-assisted laparoscopic colectomy for carcinoma.

PURPOSE: Mosapride citrate (mosapride) is a serotonin 5-hydroxytryptamine 4 receptor agonist known to promote gastric emptying and large-intestine motility. We assessed the effect of mosapride on postoperative ileus following colon surgery. METHODS: Forty patients with colon cancer undergoing hand-assisted laparoscopic colectomy were randomly assigned to a mosapride group or a control group. The mosapride group received 15 mg of mosapride by mouth with 50 ml of water three times a day, starting on postoperative day 1. The control group received 50 ml of water on the same schedule. Patients were allowed to resume oral feeding on the evening of postoperative day 2. Postoperative time to first bowel movement was evaluated by one investigator blinded to treatment. Postoperative gastric emptying was evaluated with the [(13)C]-acetate breath test at 24 and 48 hours after the operation. RESULTS: Postoperative time to first bowel movement was significantly shorter in the mosapride group than in the control group (48.5 vs. 69.3 hours, P = 0.0149). The time to maximal gastric emptying rate as determined by the breath test was significantly shorter in the mosapride group than in the control group at the 48-hour time point (27.9 vs. 35.3 minutes, P = 0.0294). Postoperative hospital stay was shorter in patients receiving mosapride than in controls (6.7 vs. 8.4 days, P = 0.0398). No adverse effects were observed with mosapride. CONCLUSIONS: Gastric emptying was improved by mosapride. The results suggested that the period of postoperative ileus following hand-assisted laparoscopic colectomy can be shortened by treatment with mosapride.

Microencapsule technique protects hepatocytes from cryoinjury.

AIM: Hepatocyte transplantation is a potential alternative to whole organ liver transplantation. To realize this procedure, a hepatocyte bank system capable of supplying large numbers of hepatocytes must be established. We previously reported an easy method for cryopreserving hepatocytes using a microencapsulation technique. Here, we investigated how cryoinjury to microencapsulated hepatocytes could be avoided during cryopreservation. METHODS: Hepatocytes from Sprague-Dawley rats were harvested in situ using a two-step ethylenediaminetetraacetic acid (EDTA)/collagenase digestion protocol. The cells were microencapsulated using alginate-poly L-lysine. The microencapsulated hepatocytes were put into vials and immediately immersed in liquid nitrogen. The growth of ice crystals in the vials containing the microencapsulated hepatocytes was observed using cryomicroscopy. The microencapsulated hepatocytes were sectioned for ultrastructural examination to investigate their intracellular conditions. Finally, total RNA was isolated from the cryopreserved microencapsulated hepatocytes and analyzed for hepatocyte nuclear factor (HNF) using reverse transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS: Cryomicroscopy showed that the alginate microencapsulation technique protected the hepatocytes from physical damage caused by the growth of extracellular ice crystals. Ultrastructural examination revealed that the intracellular environment of the microencapsulated hepatocytes was maintained. The RT-PCR analysis additionally suggested that the alginate gel also maintained the HNF level. CONCLUSION: Our microencapsulation technique protects hepatocytes from cryoinjury. This novel technique could be utilized by hepatocyte banks.

Sentinel node mapping guided by indocyanine green fluorescence imaging: a new method for sentinel node navigation surgery in gastrointestinal cancer.

BACKGROUND: Recently, gastrointestinal cancer has also been identified as a target for sentinel node navigation surgery (SNNS). This study is the first to determine the feasibility of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in gastrointestinal cancer. METHODS: Our series consisted of 22 patients with gastric cancer and 26 patients with colorectal cancer who had undergone standard surgical resection. ICG solution was injected intraoperatively into the subserosa around the tumor. Fluorescence imaging was obtained by a charge-coupled device (CCD) camera with a light-emitting diode with a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. RESULTS: Immediately after the ICG injection, lymphatic vessels draining the tumor and round-shaped SNs were visualized by their bright fluorescence. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. The SN detection rate and mean number of SNs were 90.9% and 3.6 +/- 4.5 (mean +/- SD), respectively, in patients with gastric cancer, and 88.5% and 2.6 +/- 2.4, respectively, in patients with colorectal cancer. Among the patients with gastric cancer, the accuracy and false-negative rates were 88.9 and 33.3%, respectively, in patients with T(1) stage cancer, and 70.0 and 60.0%, respectively, overall, in all the patients. Among the patients with colorectal cancer, the corresponding values were 100 and 0%, respectively, in patients with T(1) stage cancer, and 82.6 and 66.7%, respectively, overall, in all the patients. CONCLUSIONS: Our preliminary results show that ICG fluorescence imaging allows easy, highly sensitive and real-time imaging-guided SN mapping in patients with gastric or colorectal cancer. SN mapping guided by ICG fluorescence imaging could be a promising tool deserving further clinical exploration.