Safety and tolerability of bone marrow-derived mesenchymal stem cells in lupus animal models and a phase I clinical trial in humans.

OBJECTIVE: Several clinical trials aimed at treating various autoimmune diseases, including systemic lupus erythematosus (SLE), by introducing mesenchymal stem cells (MSCs) have been conducted. However, with refractory lupus nephritis (LN), the outcomes of MSC transplantation are not well known, and further validation is required. In particular, data concerning the safety and efficacy of LN treatment using bone marrow-derived MSCs (BM-MSCs) are still lacking. METHODS: We identified characteristics of BM-MSCs in terms of cell morphology, chromosomal stability, differentiation capacity, and phenotype through cell passages. The in vivo stability of BM-MSCs was evaluated by single-dose and repeated-dose toxicity tests, tumorigenicity tests, and biodistribution tests using lupus mouse models. Based on the encouraging nonclinical results, we conducted a nonrandomized, open-label, single-arm phase I clinical trial to evaluate the tolerability and safety of a single administration of haploidentical allogeneic BM-MSCs (CS20AT04) in seven LN patients (NCT03174587). We used a classical three + three design to find the optimal dosage. The starting dose was 2.0×106 cells/kg and escalated to 3.0×106 cells/kg if there was no dose-limiting toxicity (DLT). Evaluation of the safety and tolerability was assessed 28 days after the infusion, and the maximum tolerated dose was determined. RESULTS: Properly cultured BM-MSCs showed high proliferation and multipotency, but chromosomal changes were not found. There were two deaths by a rapid administration rate in the high-dose group (2.0×106 cells/head) in a single administration test. BM-MSCs were distributed in the kidneys until Day 7. In the phase I clinical trial, seven LN patients were enrolled. Participants received BM-MSCs through intravenous infusion. There was no DLT at both initial dose (2.0×106 cells/kg) and escalated dose (3.0×106 cells/kg). One patient was not administered the full 2.0×106 cells/kg dose because of a technical error during infusion. This patient did not show DLT. Three adverse events were reported, namely, one diarrhea, one toothache, and one arthralgia, and all were considered NCI-CTC grade I events. CONCLUSION: We defined the characteristics of BM-MSCs and identified their safety and tolerability in both animal models and a phase I clinical trial. The maximum tolerated dose was determined to be 3.0×106 cells/kg in patients with LN.

Ganglion cysts developed from the flexor tendon sheaths in the fingers: Clinical and sonographic features.

PURPOSE: The purpose of this study was to assess the clinical and sonographic features of flexor tendon sheath ganglion cysts in the fingers. METHODS: We retrospectively reviewed the clinical and sonographic features of 35 cases of flexor tendon sheath ganglion cysts in the fingers in 34 patients that were pathologically confirmed between 2003 and 2018. RESULTS: The mean age of the patients was 44.2 years (range, 11-73 years). Lesions were located at the level of the metacarpophalangeal joint (n = 22 [63%]) and proximal phalanx (n = 11 [31%]), and involvement of the third finger was common (n = 19 [54%]). The mean lesion size was 6 mm and the mean volume was 90 mm3 . None of the lesions had a pedicle. Lesions were homogeneous (n = 24 [69%]) and anechoic (n = 23 [66%]). A septum was noted in 12 cases (34%). CONCLUSIONS: Flexor tendon sheath ganglion cysts are most commonly located in the third finger and at the level of the metacarpophalangeal joint and proximal phalanx. It usually presents as a simple cyst without a pedicle, but occasionally exhibits a mixed echogenicity and contains a septum.

Clinical role of 18F-FDG PET-CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging.

OBJECTIVES: This study was conducted to evaluate the clinical role of integrated positron emission and computed tomography (PET-CT) in patients with suspected and potentially operable cholangiocarcinoma. METHODS: Between October 2005 and May 2007, 123 patients with suspected cholangiocarcinoma were enrolled in this study after diagnostic workup, including biliary dynamic computed tomography (CT) and magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) with magnetic resonance (MR) angiography. Patients with overt unresectable cholangiocarcinoma or gallbladder cancer diagnosed via conventional imaging were excluded. Consecutively, each enrolled patient underwent PET-CT. Data were prospectively collected and analyzed in comparison with CT and MRI/MRCP. RESULTS: The overall values for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET-CT in primary tumor detection were 84.0%, 79.3%, 92.9%, 60.5%, and 82.9%, respectively. PET-CT demonstrated no statistically significant advantage over CT and MRI/MRCP in the diagnosis of primary tumor. According to different morphologic characteristics of cholangiocarcinoma, PET-CT showed no significant difference in detecting those of mass-forming, periductal-infiltrating, and intraductal-growing types. PET-CT revealed significantly higher accuracy over CT in the diagnosis of regional lymph nodes metastases (75.9%vs 60.9%, P= 0.004) and distant metastases (88.3%vs 78.7%, P= 0.004). Additional use of PET-CT for assessing resectability correctly showed different results from those determined by conventional imaging in 15 (15.9%) of 94 patients with cholangiocarcinoma. CONCLUSIONS: PET-CT improved the accuracy of preoperative staging in patients with cholangiocarcinoma planning to undergo curative resection. Thus, PET-CT had an important clinical impact on the selection of proper treatment.

Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study.

OBJECTIVES: There is a wide variation in risk factors for intrahepatic cholangiocarcinoma (ICC) among various populations. Several studies have suggested that hepatitis C virus (HCV) infection may play a role in the development of ICC, whereas the role of hepatitis B virus (HBV) infection is less clear. METHODS: To determine whether HBV or HCV infection is a risk factor of ICC, we compared baseline demographic and clinical factors in 622 patients diagnosed between 2000 and 2004 with histologically confirmed ICC and 2,488 healthy controls, matched 4:1 with ICC patients for sex and year of birth. RESULTS: HBV infection (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.6-3.3), but not HCV infection, was significantly related to ICC. Other significant risk factors for ICC included liver cirrhosis (OR 13.6), heavy alcohol consumption (OR 6.6), diabetes (OR 3.2), Clonorchis sinensis infection (OR 13.6), hepatolithiasis (OR 50.0), and choledochal cysts (OR 10.7). CONCLUSIONS: Our results indicate that development of ICC seems to be more closely related to HBV infection than to HCV infection in Korea, where both HBV and ICC are endemic.