No abstract

Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. STEM

The incidence of anastomotic leakage after low anterior resection is relatively low. Male gender and preoperative CCRT were associated with increased risk for anastomotic leakage after rectal cancer surgery. No effect of anastomosis leakage on local recurrence was found in this series.

The present study was designed to evaluate the safety and potential of adipose tissue-derived stem cells (ASCs) for the treatment of Crohn's fistula. In this dose escalation study, patients were sequentially enrolled into three dosing groups with at least three patients per group. The first three patients (group 1) were given 1 ´ 10 7 cells/ml. After 4 weeks, this dose was deemed safe, and so an additional four patients (group 2) were given 2 ´ 10 7 cells/ml. Four weeks later, after which this second dose was deemed safe, a third and final group of three patients were given 4 ´ 10 7 cells/ml. Each patient was followed for a minimum of 8 weeks. Patients who showed complete healing at week 8 were followed up for an additional 6 months. Efficacy endpoint was complete healing at week 8 after injection, defined as complete closure of the fistula track and internal and external openings without drainage or signs of inflammation. There were no grade 3 or 4 severity adverse events, and there were no adverse events related to the study drug. Two patients in group 2, treated with 2 ´ 10 7 ASCs/ml, showed complete healing at week 8 after injection. Of the three patients enrolled in group 3, treated with 4 ´ 10 7 ASCs/ml, one showed complete healing. Outcome in another patient was assessed as partial healing due to incomplete closure of the external opening, although the inside of fistula track was filled considerably and there was no drainage. All three patients with complete healing at week 8 showed a sustained effect without recurrence 8 months after injection. In conclusion, this study demonstrates the tolerability, safety, and potential efficacy of ASCs for the treatment of Crohn's fistula and provides support for further clinical study.

A previous phase II clinical trial of adipose-derived stem cell (ASC) therapy for fistulae associated with Crohn's disease, a devastating condition with a high recurrence rate, demonstrated safety and therapeutic potential with a 1-year sustained response. In the present study, 41 of the 43 phase II trial patients were followed for an additional year, regardless of response in the initial year. At 24 months, complete healing was observed in 21 of 26 patients (80.8%) in modified per protocol analysis and 27 of 36 patients (75.0%) in modified intention-to-treat analysis. No adverse events related to ASC administration were observed. Furthermore, complete closure after initial treatment was well-sustained. These results strongly suggest that autologous ASCs may be a novel treatment option for Crohn's fistulae.

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Positron emission tomography (PET) using F-18 fluoro-2-deoxy-d-glucose ( 18 F-FDG) is now well established as a noninvasive diagnostic tool for the detection of a variety of malignant tumors. However, in the case of hepatocellular carcinoma (HCC), several investigators have reported controversial conclusions and an inadequate sensitivity for PET (50-55%). Nevertheless, a high positive rate of 18 F-FDG accumulation has been reported in patients with high-grade HCC and in those with markedly elevated alpha-fetoprotein (AFP) levels. Here, we retrospectively reviewed 38 HCC cases that received liver transplantation (LT) at our center between November 2000 and July 2004 and underwent whole-body PET imaging.18 F-FDG uptake was assessed in the liver, and its prognostic significance was investigated. Of 38 patients enrolled, 13 patients had positive PET scans for a liver tumor. When we analyzed the association between tumor factors and PETϩ (greater PET lesion uptake) in the liver, preoperative AFP level and vascular invasion were found to be significantly associated with PETϩ (P ϭ 0.003 and P Ͻ 0.001, respectively). However, the association between histological grade and PETϩ findings did not reach statistical significant difference (P ϭ 0.074). Moreover, the 2-year recurrence-free survival rate of PETϪ patients was significantly higher than that of PETϩ patients (85.1% vs. 46.1%) (P ϭ 0.0005). Of 6 PETϩ patients who met the Milan criteria, 4 patients (66.7%) had recurrence, but all 20 PETϪ patients who met the Milan criteria were recurrence free. Thus, PET imaging could be a good preoperative tool for estimating the post-LT risk of tumor recurrence, because histological grade and vascular invasion cannot be determined preoperatively. Importantly, our results indicate that tumor recurrence can be highly anticipated for PETimaging-positive HCC patients who satisfy the Milan criteria. We advise that PETϩ HCC patients be selected cautiously for LT.

Mucinous adenocarcinoma (MAC) is a histological subtype of colorectal cancer. The oncologic behavior of MAC differs from nonmucinous adenocarcinoma (non-MAC). Our aim in this study was to characterize patients with colorectal MAC through evaluation of a large, institutional-based cohort with long-term follow-up.A total of 6475 patients with stages I to III colorectal cancer who underwent radical surgery were enrolled from January 2000 to December 2010. Prognostic comparison between MAC (n = 274, 4.2%) and non-MAC was performed.The median follow-up period was 48.0 months. Patients with MAC were younger than those without MAC (P = 0.012) and had larger tumor size (P < 0.001), higher preoperative carcinoembryonic antigen (P < 0.001), higher pathologic T stage (P < 0.001), more right-sided colon cancer (49.3%, P < 0.001), and more frequent high-frequency microsatellite instability (10.2%, P < 0.001). Five-year disease-free survival (DFS) was 76.5% in the MAC group and 83.2% in the non-MAC group (P = 0.008), and 5-year overall survival was 81.4% versus 87.4%, respectively (P = 0.005). Mucinous histology (MAC vs non-MAC) in the entire cohort was not an independent prognostic factor of DFS but had a statistical tendency (P = 0.071). In subgroup analysis of colon cancer without rectal cancer, mucinous histology was an independent prognostic factor (P = 0.026).MAC was found at more advanced stage, located mainly at the right side and was an independent factor of survival in colon cancer. Because of the unique biological behavior of MAC, patients with MAC require special consideration during follow-up.