[Experience of Introduction of Robotic-Assist Surgery at Regional Hospital].

Our hospital introduced the da Vinci Xi Surgical System in April 2022. At the same time, laparoscopic surgery was also introduced to produce endoscopic surgical skill qualification system: qualified surgeon. Open surgery for trainees was also continued as before, and young surgeons were instructed to always keep their motivation high. After the introduction of robotic surgery, conferences that were accessible to trainees were held on a regular basis. In addition, the environment was designed to allow anyone to train da Vinci Surgical System. The introduction of robotic surgery has certainly reduced the number of procedures performed by trainees, especially in rectal cancer. However, surgical outcomes were better after the introduction of robotic surgery. The trend was similar for both open and laparoscopic surgery. We report on our efforts to introduce robot-assisted surgery and the actual situation in which surgeons at various stages of their education can work together to achieve a win-win situation.

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study.

PURPOSE: We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. METHODS: Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. RESULTS: A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). CONCLUSIONS: Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.

Oxaliplatin-induced increase in splenic volume: experiences from multicenter study in Japan.

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.

A Japanese multicenter phase II study of adjuvant chemotherapy with mFOLFOX6/CAPOX for stage III colon cancer treatment after D2/D3 lymphadenectomy.

PURPOSE: A phase II trial was conducted to investigate the benefit of oxaliplatin-based adjuvant chemotherapy in Japanese stage III colon cancer patients. METHODS: Eligible patients were scheduled to receive 12 cycles of mFOLFOX6 or 8 cycles of CAPOX in adjuvant settings. The primary endpoint was the 3-year disease-free survival (DFS). Cox proportional hazards regression was performed to identify risk factors for a worse DFS. RESULTS: A total of 130 patients, including 73 patients receiving mFOLFOX6 and 57 patients receiving CAPOX, were enrolled from 16 institutions between April 2010 and April 2014. The 3-year DFS was 82.2%, exceeding the expected primary endpoint of 81.7%. The 3-year DFS tended to be higher in patients receiving mFOLOFOX6 than in those receiving CAPOX (mFOLFOX6, 86.3%; CAPOX, 76.9%; P = 0.06). The 3-year DFS rates did not differ markedly based on the risk stratification (T1/T2/T3 N1 vs. T4 or N2) indicated by the IDEA COLLABORATION study (P = 0.22). In the multivariate analysis, stage IIIC (P = 0.046) and early discontinuation (P < 0.01) were identified as independent significant risk factors for a worse DFS. CONCLUSION: Our findings represent the first positive results in a Japanese phase II trial of adjuvant chemotherapy with mFOLFOX6/CAPOX. Early discontinuation within 2 months was an independent risk factor for a shorter DFS.

A Pilot Trial to Quantify Plasma Exosomes in Colorectal Cancer Screening from the International Collaborative Study between Chile and Japan.

BACKGROUND: In Chile, a national colorectal cancer (CRC) screening program using immunochemical fecal occult blood tests and colonoscopy was started in 2012 as an international collaboration between Chile and Japan. In the present study, we quantified exosomes in the peripheral blood and evaluated the implication of the results for CRC screening. METHODS: A total of 25 peripheral plasma samples from the participants of CRC screening in Punta Arenas, Chile, were analyzed for exosomes. RESULTS: Plasma exosomes were obtained from 5 participants with adenocarcinoma (4 pTis and 1 pT1), 8 with high-grade adenoma, 4 with low-grade adenoma, 4 with hyperplastic polyps, and 4 with normal findings. Participants with adenocarcinoma had significantly higher amounts of plasma exosomes (2.1-3.2 fold) than participants with normal findings, hyperplastic polyps, or low-grade adenoma (p = 0.016, p = 0.0034, and p = 0.0042 respectively; Tukey's multiple comparisons test). The size of the representative lesion, the number of lesions, and the sum of those 2 factors in each participant correlated significantly with the exosome amounts (r = 0.56, r = 0.58, and r = 0.72, respectively; p < 0.01; Spearman's correlation coefficient test). CONCLUSIONS: This pilot study demonstrated that quantification of plasma exosomes is a potential alternative screening method for detecting individuals with a high risk of colorectal malignancy.

[Results of a multicentric colorectal cancer screening program in Chile]. / Programa multicéntrico de cribado de cáncer colorrectal en Chile.

BACKGROUND: Colorectal Cancer Screening Programs (CRCSP) are widely accepted in developed countries. Unfortunately, financial restrictions, low adherence rate and variability on colonoscopy standardization hamper the implementation of CRCSP in developing countries. AIM: To analyze a multicentric pilot model of CRCSP in Chile. MATERIAL AND METHODS: A prospective model of CRCSP was carried out in three cities, from 2012 to 2015. The model was based on CRC risk assessment and patient education. Health care personnel were trained about logistics and protocols. The endoscopy team was trained about colonoscopy standards. A registered nurse was the coordinator in each center. We screened asymptomatic population aged between 50 and 75 years. Immunological fecal occult blood test (FIT) was offered to all participants. Subjects with positive FIT underwent colonoscopy. RESULTS: A total of 12,668 individuals were enrolled, with a FIT compliance rate of 93.9% and 2,358 colonoscopies were performed. Two hundred and fifty high-risk adenomas and 110 cancer cases were diagnosed. One patient died before treatment due to cardiovascular disease, 74 patients (67%) underwent endoscopic resection and 35 had surgical treatment. Ninety one percent of patients had an early stage CRC (0-I-II). Among colonoscopy indicators, 80% of cases had an adequate bowel preparation (Boston > 6), cecal intubation rate was 97.7%, adenoma detection rate was 36.5%, and in 94.5% of colonoscopies, withdrawal time was adequate (> 8 min). CONCLUSIONS: This CRCS pilot model was associated to a high rate of FIT return and colonoscopy quality standards. Most CRCs detected with the program were treated by endoscopic resection.

International collaboration between Japan and Chile to improve detection rates in colorectal cancer screening.

BACKGROUND: In Chile, mortality from colorectal cancer (CRC) has increased rapidly. To help address this issue, the Prevention Project for Neoplasia of the Colon and Rectum (PRENEC) program was initiated in 2012 with intensive support from Tokyo Medical and Dental University (TMDU) in Tokyo, Japan, as part of an international collaboration. METHODS: From June 2012 to July 2014, a total of 10,575 asymptomatic participants were enrolled in PRENEC. Participants with positive immunochemical fecal occult blood test (iFOBT) results or a family history of CRC underwent colonoscopy. The colonoscopy results from a similar, previous project in Chile (PREVICOLON) were compared with those from PRENEC. Furthermore, the initial colonoscopies of 1562 participants in PRENEC were analyzed according to whether the colonoscopists were from TMDU or Chile. RESULTS: The complete colonoscopy, adenoma detection, and cancer detection rates were 88.0%, 26.7%, and 1.1%, respectively, in PREVICOLON, while the corresponding values were 94.4%, 41.8%, and 6.0%, respectively, in PRENEC. In PRENEC, 107 cases of CRC were detected, amounting for 1.0% of all participants. Considering initial colonoscopies in PRENEC, the complete colonoscopy, adenoma detection, and cancer detection rates were 97.4%, 45.3%, and 9.3%, respectively, for physicians at TMDU and 93.3%, 41.5%, and 5.1%, respectively for Chilean physicians. The detection rates of intramucosal cancer were 7.3% and 3.7%, respectively, for TMDU and Chilean physicians. CONCLUSIONS: Quality indicators of colonoscopy substantially improved from PREVICOLON to PRENEC. The assessments made by Chilean physicians alone were improved in PRENEC, but remained better in the TMDU group. Moreover, physicians from TMDU detected more CRCs than Chilean physicians, especially at earlier stages.

[Laparoscopic Gastrectomy for Gastric Adenocarcinoma of the Fundic Gland Type - Report of a Case].

A 69-year-old man underwent esophagogastroduodenoscopy, which showed a slightly depressed lesion at the greater curvature of the gastric body. We diagnosed gastric adenocarcinoma of the fundic gland type(GA-FG)from examination of the biopsy specimen. Endoscopic submucosal dissection(ESD)was performed for curative resection. The pathological examination revealed a positive vertical margin. Consequently, laparoscopic gastrectomy was additionally performed. GA-FG has recently been proposed as a new entity of gastric adenocarcinoma. GA-FG mostly develops without Helicobacter pylori infection and often invades the submucosa, regardless of size. However, GA-FG rarely demonstrates lymphatic and venous invasion despite deep submucosal invasion. Since most GA-FG cases undergo ESD, few reports of surgical resection exist. Here, we report our experience of laparoscopic gastrectomy for GA-FG.

A phase II trial of perioperative chemotherapy involving a single intraperitoneal administration of paclitaxel followed by sequential S-1 plus intravenous paclitaxel for serosa-positive gastric cancer.

BACKGROUND AND OBJECTIVES: We carried out a phase II trial to evaluate the feasibility, efficacy, and tolerability of perioperative chemotherapy including single intraperitoneal(IP) administration of paclitaxel(PTX) followed by intravenous(IV) administrations of PTX with S-1 in a neoadjuvant setting for serosa-positive gastric cancer. METHODS: Patients with cT4a gastric cancer were enrolled. A laparoscopic survey was performed before study inclusion for the confirmation of serosal invasion, negative lavage cytology, and negative peritoneal metastasis. IP PTX (80 mg/m(2)) was administered, followed by systemic chemotherapy. Surgery was performed after the completion of chemotherapy. The primary endpoint was the treatment completion rate. RESULTS: 37 patients were recruited. The treatment completion rate was 67.6% (25/37; 90% CI, 52.8-80.1%), which was significantly higher than 50%; we set this as a threshold value (P = 2.4% [one-sided]). 14 patients had target lesions; of these, 10 showed a partial response (71.4%), three had stable disease (21.4%), and one had progressive disease(7.2%). The response rate was 71.4% (10/14). All patients underwent gastrectomy with D2 lymph node dissection. The 3- and 5-year OS rates were 78.0 and 74.9%, respectively. CONCLUSIONS: Perioperative chemotherapy including neoadjuvant IP PTX followed by sequential IV PTX with S-1 for serosa-positive gastric cancer is feasible, safe, and efficient.

Appearance of neural stem cells around the damaged area following traumatic brain injury in aged rats.

We have previously reported free radical production after traumatic brain injury (TBI), which induces neural stem cell (NSC) degeneration and death. However, the effects of aging on NSC proliferation around the damaged area following TBI have not been investigated. Therefore, in this study, we used 10-week (young group) and 24-month-old (aged group) rat TBI models to investigate the effects of aging on NSC proliferation around damaged tissue using immunohistochemical and ex vivo techniques. Young and aged rats received TBI. At 1, 3 and 7 days after TBI, immunohistochemical and lipid peroxidation studies were performed. Immunohistochemistry revealed that the number of nestin-positive cells around the damaged area after TBI in the aged group decreased significantly when compared with those in the young group (P < 0.01). However, the number of 8-hydroxy-2'-deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells and the level of peroxidation around the damaged area after TBI significantly increased in the aged group, compared with those in the young group (P < 0.01). Furthermore, almost all ssDNA-positive cells in young and aged groups co-localized with NeuN and nestin staining. Ex vivo studies revealed that neurospheres, which differentiated into neurons and glia in culture, could only be isolated from injured brain tissue in young and aged groups at 3 days after TBI. These results indicate that, although there were fewer NSCs that have the potential to differentiate into neurons and glia, these NSCs escaped free radical-induced degeneration around the damaged area after TBI in the aged rat brain.

Neuroprotective effect of (-)-epigallocatechin-3-gallate in rats when administered pre- or post-traumatic brain injury.

Our previous study indicated that consuming (-)-epigallocatechin gallate (EGCG) before or after traumatic brain injury (TBI) eliminated free radical generation in rats, resulting in inhibition of neuronal degeneration and apoptotic death, and improvement of cognitive impairment. Here we investigated the effects of administering EGCG at various times pre- and post-TBI on cerebral function and morphology. Wistar rats were divided into five groups and were allowed access to (1) normal drinking water, (2) EGCG pre-TBI, (3) EGCG pre- and post-TBI, (4) EGCG post-TBI, and (5) sham-operated group with access to normal drinking water. TBI was induced with a pneumatic controlled injury device at 10 weeks of age. Immunohistochemistry and lipid peroxidation studies revealed that at 1, 3, and 7 days post-TBI, the number of 8-Hydroxy-2'-deoxyguanosine-, 4-Hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and levels of malondialdehyde around the damaged area were significantly decreased in all EGCG treatment groups compared with the water group (P < 0.05). Although there was a significant increase in the number of surviving neurons after TBI in each EGCG treatment group compared with the water group (P < 0.05), significant improvement of cognitive impairment after TBI was only observed in the groups with continuous and post-TBI access to EGCG (P < 0.05). These results indicate that EGCG inhibits free radical-induced neuronal degeneration and apoptotic death around the area damaged by TBI. Importantly, continuous and post-TBI access to EGCG improved cerebral function following TBI. In summary, consumption of green tea may be an effective therapy for TBI patients.

(-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury.

A major component of green tea is (-)-epigallocatechin gallate (EGCG), which has strong antioxidant properties. Here, we investigated the effect of EGCG on neural stem cell (NSC) proliferation around the damaged area following traumatic brain injury (TBI). In this study, male Wistar rats that had access to normal drinking water, or water containing 0.1% (w/v) EGCG, ad libitum received TBI at 10 weeks of age. Immunohistochemistry revealed that the number of nestin-positive cells around the damaged area after TBI in the EGCG treatment group increased significantly compared with the normal water group (P < 0.05). However, the number of 8-hydroxy-2'-deoxyguanosine-, 4-hydroxy-2-nonenal-, single-stranded DNA (ssDNA)-positive cells and the level of peroxidation around the damaged area after TBI significantly decreased in the EGCG treatment group when compared with the water group (P < 0.05). Furthermore, in contrast to the EGCG group, almost all ssDNA-positive cells in the water group co-localized with NeuN and nestin-staining. Ex vivo studies revealed that spheres could only be isolated from injured brain tissue in the water group at 3 days following TBI. However, in the EGCG group, spheres could be isolated at both 3 and 7 days following TBI. A greater number of spheres could be isolated from the EGCG group, which differentiated into neurons and glia in culture without basic fibroblast growth factor. These results indicate that consumption of water containing EGCG pre- and post-TBI inhibits free radical-induced degradation of NSCs, which have the potential to differentiate into neurons and glia around the area of damage following TBI.

Clinicopathological features of serrated adenocarcinoma defined by Mäkinen in dukes' B colorectal carcinoma.

OBJECTIVE: Serrated adenocarcinoma (SAC), proposed as a new pathologic type, arises predominantly in the right side of the colon and has a poorer prognosis than conventional colorectal carcinoma. The prognosis of colorectal carcinoma is variable in Dukes' B, so the aim of this study was to determine whether or not SAC has a poor prognosis in Dukes' B. METHODS: The study group comprised 64 patients who underwent surgery for colorectal carcinoma. We undertook a statistical analysis of the association of SAC and non-SAC with sex, age, histologic type, depth of tumor, location of tumor, venous invasion and lymphatic invasion. RESULTS: SACs were encountered in 17.5% of cases (n = 11). SAC had a less favorable 5-year survival than non-SAC (p = 0.0396 log-rank, Kaplan-Meier). The factors that achieved statistical significance in the univariate analysis were subsequently included in a multivariate analysis and we found that SAC was an independent factor (p = 0.027). CONCLUSIONS: SAC has a poor prognosis and is not affected by other factors confirming that SAC is an independently less favorable prognostic factor.

Exercise increases neural stem cell proliferation surrounding the area of damage following rat traumatic brain injury.

Exercise enhances neuronal stem cell (NSC) proliferation and neurogenesis. However, the effect of exercise on NSC proliferation surrounding the area of damage after traumatic brain injury (TBI) is unknown. Here, we investigate the effect of running on NSC proliferation following TBI in the rat. Wistar rats received TBI and were randomly divided into two groups: (1) non-exercise group and (2) exercise group. The exercise group ran on a treadmill for 30 min/day at 22 m/min for 7 consecutive days. Immunohistochemistry was used to monitor NSC proliferation around the damaged area, and ex vivo techniques were used to isolate NSCs from the damaged region in both groups. The number of nestin- and Ki67-positive cells observed at 3 and 7 days after TBI was significantly greater in the exercise group than in the non-exercise group (P < 0.01). Furthermore, most nestin-positive cells in the exercise group co-localized with Ki67-positive cells. In ex vivo studies, spheres could be isolated from injured brain tissue from the exercise group at 3 and 7 days following TBI, but at only 3 days in the non-exercise group. The number of spheres isolated from injured brain tissue was greater in the exercise group than in the non-exercise group. Spheres were immunopositive for nestin and comprised NSCs that could differentiate into neurons and glia. Exercise increases the proliferation of NSCs around the damaged area following TBI. Therefore, exercise therapy (rehabilitation) in the early phase following TBI is important for recuperation from cerebral dysfunction induced by TBI.

Exercise inhibits neuronal apoptosis and improves cerebral function following rat traumatic brain injury.

Exercise is reported to inhibit neuronal apoptotic cell death in the hippocampus and improve learning and memory. However, the effect of exercise on inhibition of neuronal apoptosis surrounding the area of damage after traumatic brain injury (TBI) and the improvement of cerebral dysfunction following TBI are unknown. Here, we investigate the effect of exercise on morphology and cerebral function following TBI in rats. Wistar rats received TBI by a pneumatic controlled injury device were randomly divided into two groups: (1) non-exercise group and (2) exercise group. The exercise group ran on a treadmill for 30 min/day at 22 m/min for seven consecutive days. Immunohistochemical and behavioral studies were performed following TBI. The number of single-stranded DNA (ssDNA)-positive cells around the damaged area early after TBI was significantly reduced in the exercise group compared with the non-exercise group (P < 0.05). Furthermore, most ssDNA-positive cells in the non-exercise group co-localized with neuronal cells. However, in the exercise group, a few ssDNA-positive cells co-localized with neurons. In addition, there was a significant increase in neuronal cell number and improvement in cerebral dysfunction after TBI in the exercise group compared with the non-exercise group (P < 0.05). These results indicate that exercise following TBI inhibits neuronal degeneration and apoptotic cell death around the damaged area, which results in improvement of cerebral dysfunction. In summary, treadmill running improved cerebral dysfunction following TBI, indicating its potential as an effective clinical therapy. Therefore, exercise therapy (rehabilitation) in the early phase following TBI is important for recuperation from cerebral dysfunction.

[A case report-bleeding from the ulcer of wound for mastectomy after postoperative chemotherapy with bevacizumab for Sigmoid colon cancer].

We report the case of a 65-year-old woman with a delayed radiation ulcer and bleeding caused by bevacizumab. She has been undergoing chemotherapy for advanced colon cancer for two years. She received a mastectomy and adjuvant chemoradiotherapy for right breast cancer twenty-one years ago, and colon cancer with liver metastasis was detected using PET two years ago. Since last year she has been treated with bevacizumab chemotherapy bevacizumab due to increased liver metastases. As a result, her radiation ulcer worsened and bleeding occurred repeatedly. On suspicion of an adverse event, we stopped the bevacizumab, and that improved the radiation ulcer and the bleeding. In this case, we discussed radiation induced ulcers, wound healing, and adverse events caused by bevacizumab.

Edaravone protects against apoptotic neuronal cell death and improves cerebral function after traumatic brain injury in rats.

Edaravone is a novel free radical scavenger used clinically in patients with acute cerebral infarction; however, it has not been assessed in traumatic brain injury (TBI). We investigated the effects of edaravone on cerebral function and morphology following TBI. Rats received TBI with a pneumatic controlled injury device. Edaravone (3 mg/kg) or physiological saline was administered intravenously following TBI. Numbers of 8-OHdG-, 4-HNE-, and ssDNA-positive cells around the damaged area after TBI were significantly decreased in the edaravone group compared with the saline group (P < 0.01). There was a significant increase in neuronal cell number and improvement in cerebral dysfunction after TBI in the edaravone group compared with the saline group (P < 0.01). Edaravone administration following TBI inhibited free radical-induced neuronal degeneration and apoptotic cell death around the damaged area. In summary, edaravone treatment improved cerebral dysfunction following TBI, suggesting its potential as an effective clinical therapy.

Performance of integrated FDG PET/contrast-enhanced CT in the diagnosis of recurrent colorectal cancer: Comparison with integrated FDG PET/non-contrast-enhanced CT and enhanced CT.

PURPOSE: The aim of our study was to evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using (18)F-fluorodeoxyglucose (FDG) with IV contrast for depiction of suspected recurrent colorectal cancer and to assess the impact of PET/contrast-enhanced CT findings on clinical management compared with PET/non-contrast-enhanced CT and CT component. METHODS: One hundred seventy patients previously treated for colorectal cancer underwent PET/CT consisting of non-enhanced and contrast-enhanced CT for suspected recurrence. PET/contrast-enhanced CT, PET/non-contrast-enhanced CT and enhanced CT were interpreted by two experienced radiologists by consensus for each investigation. Lesion status was determined on the basis of histopathology, radiological imaging and clinical follow-up for longer than 6 months. RESULTS: Patient-based analysis showed that the sensitivity, specificity and accuracy of PET/contrast-enhanced CT were 93.2 (69/74), 95.8 (92/96) and 94.7% (161/170), respectively, whereas those of PET/non-contrast-enhanced CT were 89.2 (66/74), 94.8 (91/96) and 92.4% (157/170), respectively, and those of enhanced CT were 79.7 (59/74), 93.8 (90/96) and 87.6% (149/170), respectively. Sensitivity and accuracy differed significantly among the three modalities (Cochran's Q test: p = 0.0004 and p = 0.0001, respectively).The findings of PET/contrast-enhanced CT resulted in a change of management for 64 of the 170 patients (38%) and had an effect on patient management in 12 patients (7%) diagnosed by enhanced CT alone and 4 patients (2%) diagnosed by PET/non-contrast-enhanced CT. CONCLUSION: Integrated PET/contrast-enhanced CT is an accurate modality for assessing colorectal cancer recurrence and led to changes in the subsequent appropriate therapy.

Improvement of cerebral function by anti-amyloid precursor protein antibody infusion after traumatic brain injury in rats.

We previously demonstrated the increased amyloid precursor protein (APP) immunoreactivity around the site of damage after traumatic brain injury (TBI). However, the function of APP after TBI has not been evaluated. In this study, we investigated the effects of direct infusion of an anti-APP antibody into the damaged brain region on cerebral function and morphological changes following TBI in rats. Three days after TBI, there were many TUNEL-positive neurons and astrocytes around the damaged region and a significantly greater number of TUNEL-positive cells in the PBS group compared with the anti-APP group found. Seven days after TBI, there were significantly a greater number of large glial fibrillary acidic protein-positive cells, long elongated projections, and microtubule-associated protein-2-positive cells around the damaged region in the anti-APP group compared with the PBS group found. Seven days after TBI, the region of brain damage was significantly smaller and the time to arrival at a platform was significantly shorter in the anti-APP group compared with the PBS group. Furthermore, after TBI in the anti-APP group, the time to arrival at the platform recovered to that observed in uninjured sham operation group rats. These data suggest that the overproduction of APP after TBI inhibits astrocyte activity and reduces neural cell survival around the damaged brain region, which speculatively may be related to the induction of Alzheimer disease-type dementia after TBI.

The relationship between SDF-1alpha/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats.

OBJECTIVE: The actual relationship between neural stem cells and SDF-1alpha/CXCR4 after brain injury has not yet been elucidated, although recent studies have speculated that stromal cell-derived factor-1alpha (SDF-1alpha) and its receptor, CXCR4, could contribute to neural stem cells migration after brain injury. In the present study, the temporal relationship between neural stem cells (NSCs) and SDF-1alpha/CXCR4 around a damaged area was investigated using a rat traumatic brain injury (TBI) model. METHODS: We used molecular biology techniques and immunohistochemistry to investigate the relationship between SDF-1alpha/CXCR4 expression and NSCs existence around a damaged area after TBI in the rat brain. RESULTS: SDF-1alpha mRNA expression and SDF-1alpha protein synthesis did not increase after TBI. However, SDF-1alpha leaked from the injured area and diffused into the cortex 1-3 days after TBI. Subsequently, the levels of CXCR4 mRNA expression and CXCR4 protein synthesis increased significantly. Many small cells with a nestin-positive cytoplasm and fibers also showed immunopositivity for both CXCR4 and SOX-2, but not for GFAP, 3-7 days after TBI. Moreover, a proportion of the CXCR4-positive cells and fibers also showed immunostaining for neurofilaments. DISCUSSION: These results suggest that the leaked SDF-1alpha attracted CXCR4-positive NSCs as well as elongated nerve fibers. It is considered that the SDF-1alpha/CXCR4 system in the brain contributes to neural stem cells appearance and maturation after TBI. Therefore, exploitation of the SDF-1alpha/CXCR4 system around a damaged area may improve the brain dysfunction after TBI.