Machine learning-based identification of hip arthroplasty designs.

BACKGROUND: The purposes of this study were to develop a machine learning-based implant recognition program and to verify its accuracy. METHODS: Postoperative anteroposterior (AP) X-rays (≥300 dpi) were collected of patients who underwent total hip arthroplasty. X-rays with a wire or plate added and those without a true anteroposterior view were excluded. A total of 170 X-ray images of hip implants from 29 brands were collected from five hospitals and a Google image search. These collected images were manually reorganised to ensure appropriate labelling. Collected images were preprocessed to have grey-scaled pixels with histogram equalisation for efficient training. Images varied by +10/-10°, and 3606 unique images derived from the original 170 images were created for training. Discussion of the validation set being derived 25% of training set. The recognition model structure consisted of two steps: object detection and clustering. Model training was performed with Keras deep learning platform. RESULTS: The 170 X-ray images of hip implants were used to build a stem detection model using YOLOv3. Manually labelled images were successfully trained into the stem detection model. Evaluation of 58 newly labelled X-ray images showed highly accurate stem detection (mean average precision > 0.99). Fully connected layers generated 29 class outputs. After training, a receiver operating characteristic curve was generated with a test set containing 25% of all stem-cropped images, yielding an area under the curve of 0.99. CONCLUSION: Femoral stem identification in patients with total hip arthroplasty was very accurate. This technology could be used to collect large-scale implant information. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This program has the following clinical relevance. First, we can prepare the implants needed for revision surgery by identifying the old types of implants. Second, it can be used to diagnose peripheral osteolysis or periprosthetic fracture by further developing the ability to sensitise implant detection. Third, an automated implant detection system will help organise imaging data systematically and easily for arthroplasty registry construction.

Imaging diagnosis of post-ERCP focal pancreatitis mimicking pancreatic carcinoma by follow-up F-18 FDG PET/CT.

Pancreatitis is the most common complication of diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The incidence of clinical post-ERCP pancreatitis is about 5%. The authors describe a case of 60-year-old man who developed an unusual focal, instead of usual diffuse pancreatitis after diagnostic ERCP. F-18 FDG PET/CT in 3 days after ERCP detected focal FDG uptake because of pancreatitis, and the diagnosis was confirmed by spontaneous resolution of the lesion on 1-week follow-up PET/CT study.

Depletion of L-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes.

PURPOSE: L-ascorbic acid (LAA) modifies the in vitro growth of leukemic cells from approximately 50% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). To test the hypothesis that depletion of LAA, alternating with supplementation to prevent scurvy, would provide therapeutic benefit, a single-arm pilot trial was conducted (ClinicalTrials.gov identifier: NCT00329498). Experimental results: During depletion phase, patients with refractory AML or MDS were placed on a diet deficient in LAA; during supplementation phase, patients received daily intravenous administration of LAA. An in vitro assay was performed pretherapy for LAA sensitivity of leukemic cells from individual patients. RESULTS: Of 18 patients enrolled, eight of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (four patients) as well as during supplementation (five patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the in vitro assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared with none of six patients who were insensitive to LAA. CONCLUSIONS: The clinical benefit, along with a conspicuous absence of significant adverse events, suggests that further testing of LAA depletion alternating with pharmacologic dose intravenous supplementation in patients with these and other malignancies is warranted.

Enhancement of plasmacytoma cell growth by ascorbic acid is mediated via glucose 6-phosphate dehydrogenase.

PURPOSE: We investigated the mechanism by which some types of cancer cells grow faster in the presence of ascorbic acid supplementation. MATERIALS AND METHODS: Adj.PC-5, a mouse plasmacytoma cell, is known to show ascorbic acid-dependent growth and was chosen as a test system. The growth of cancer cells was measured by the colony number on soft agar or the cellular proliferation in suspension culture. The ascorbate level was measured by a high performance liquid chromatography system with an electrochemical detector. Glucose 6-phosphate dehydrogenase was analyzed both on the specific enzyme activity level and on the transcription level by performing Northern blot analysis. RESULTS: Ascorbyl 2-phosphate among the ascorbate derivatives was the most efficient in stimulating cell growth. The intracellular and extracellular ascorbate concentrations following treatment with either ascorbate or ascorbyl 2-phosphate suggest that the superiority of ascorbyl 2-phosphate for stimulating cell growth may be due to its slow conversion to ascorbate in the culture medium. The steady transformation to ascorbate ensures sustained levels of ascorbate in the culture medium and thereby maximizes the growth stimulatory effect of ascorbate. Ascorbyl 2-phosphate markedly enhanced, in a concentration-and time-dependent manner, mRNA synthesis as well as the enzymatic activity of glucose 6-phosphate dehydrogenase, which is known to be a rate-limiting enzyme in cell growth. On the other hand, simultaneous addition of dehydroisoandrosterone, a well- known inhibitor of glucose 6-phosphate dehydrogenase, to the culture medium abrogated the growth stimulation by ascorbyl 2-phosphate, and it also reduced the glucose 6-phosphate dehydrogenase activity proportionately. CONCLUSIONS: The results from this study suggest that enhanced glucose 6-phosphate dehydrogenase activity may at least in part explain the stimulation of cell growth by ascorbate or ascorbyl 2-phosphate.

Activation of Raf1 and the ERK pathway in response to l-ascorbic acid in acute myeloid leukemia cells.

L-ascorbic acid (LAA) shows cytotoxicity and induces apoptosis of malignant cells in vitro, but the mechanisms by which such effects occur have not been elucidated. In the present study, we provide evidence that the ERK MAP kinase pathway is activated in response to LAA (< 1 mM) in acute myeloid leukemia cell lines. LAA treatment of cells induces a dose-dependent phosphorylation of extracellular signal-regulated kinases (ERK) and results in activation of its catalytic domain. Our data also demonstrate that the small G protein Raf1 and MAPK-activated protein kinase 2 are activated by LAA as an upstream and a downstream regulator of ERK, respectively. Although the ERK pathway has been known to activate cell proliferation, pharmacologic inhibition of ERK reduces LAA-dependent apoptosis and growth inhibitory response of acute myeloid leukemia cell lines, suggesting that this signaling cascade positively regulates induction of apoptotic response by LAA.

Arsenic trioxide represses constitutive activation of NF-kappaB and COX-2 expression in human acute myeloid leukemia, HL-60.

It has been proposed that eukaryotic nuclear factor nuclear factor kappa-B (NF-kappaB) and cyclooxygenase-2 (COX-2) are implicated in the pathogenesis of many human diseases including cancer. Arsenic has been widely used in medicine in Oriental countries. Recent studies have shown that arsenic trioxide (As(2)O(3)) could induce in vitro growth inhibition and apoptosis of malignant lymphocytes, and myeloma cells. However, the molecular mechanisms by which As(2)O(3) initiates cellular signaling toward cell death are still unclear. In the present study, the effects of As(2)O(3) on NF-kappaB and COX-2 expression in HL-60 cells were investigated. As(2)O(3) suppressed DNA-binding activity of NF-kappaB composed of p65/p50 heterodimer through preventing the degradation of IkappaB-alpha and the nuclear translocation of p65 subsequently as well as interrupting the binding of NF-kappaB with their consensus sequences. Inhibitory effect of As(2)O(3) on NF-kappaB DNA activity was dependent upon intracellular glutathione (GSH) and H(2)O(2) level, but not superoxide anion. Futhermore, we found that As(2)O(3) also downregulated the expression of COX-2, which has NF-kappaB binding site on its promoter through repressing the NF-kappaB DNA-binding activity.

Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen.

The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.

L-ascorbic acid represses constitutive activation of NF-kappaB and COX-2 expression in human acute myeloid leukemia, HL-60.

There is increasing evidence that L-ascorbic acid (LAA) is selectively toxic to some types of cancer cells at pharmacological concentrations, functioning as a pro-oxidant rather than as an anti-oxidant. However, the molecular mechanisms by which LAA initiates cellular signaling leading to cell death are still unclear. In an effort to gain insight into these mechanisms, the effects of LAA on eukaryotic transcription nuclear factor NF-kappaB and cyclooxygenase-2 (COX-2) expression were investigated. In the present study, LAA suppressed DNA binding activity of NF-kappaB, composed of a p65/p50 heterodimer, through inhibition of degradation of inhibitory kappaB-alpha (IkappaB-alpha) and prevention of nuclear translocation of p65. The inhibitory effect of LAA on NF-kappaB activity was dependent upon glutathione levels in HL-60 cells, as well as generation of H2O2 but not superoxide anion. LAA also downregulated the expression of COX-2, which has a NF-kappaB binding site on its promoter, through repressing NF-kappaB DNA binding activity. Moreover, cotreatment of 1 microM arsenic trioxide (As2O3) with various concentrations of LAA enhanced an LAA-induced repression of NF-kappaB activity and COX-2 expression. In conclusion, our data suggest that LAA exerts its anti-tumor activity through downregulation of NF-kappaB activity and COX-2 expression, and these inhibitory effects can be enhanced by co-treatment with As2O3.

L-Ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide-mediated mechanisms.

L-Ascorbic acid (LAA) is being investigated clinically for the treatment of patients with acute myeloid leukemia (AML) based on the observed effects of LAA on AML progenitor cells in vitro. However, the mechanism for LAA-induced cytoreduction remains to be elucidated. LAA at concentrations of 0.25-1.0 mM induced a dose- and time-dependent inhibition of proliferation in three AML cell lines and also in leukemic cells from peripheral blood specimens obtained from three patients with AML. In contrast, ovarian cancer cell lines were only minimally affected. Flow cytometric analysis showed that LAA at concentrations of 0.25-1.0 mM could significantly induce apoptosis in the AML cell lines. LAA induced oxidation of glutathione to oxidized form (GSSG) and subsequent H(2)O(2) accumulation in a concentration-dependent manner, in parallel to induction of apoptosis. The direct role of H(2)O(2) in the induction of apoptosis in AML cells was clearly demonstrated by the finding that catalase could completely abrogate LAA-induced apoptosis. Induction of apoptosis in LAA-treated AML cells involved a dose-dependent increase of Bax protein, release of cytochrome C from mitochondria to cytosol, activation of caspase 9 and caspase 3, and cleavage of poly[ADP-ribose]polymerase. In conclusion, LAA can induce apoptosis in AML cells, and this is clearly due to H(2)O(2) which accumulates intracellularly as a result of oxidation of reduced glutathione by LAA.

Oxaliplatin and UFT combination chemotherapy in patients with metastatic colorectal cancer.

A phase II study was performed to evaluate the clinical efficacy and toxicity of oxaliplatin combined with uracil and tegafur (UFT) in patients with advanced colorectal cancer previously treated with a fluoropyrimidine-based regimen. From January to December 1999, 34 patients were enrolled in this study. Patients received intravenous oxaliplatin 130 mg/m2 on day 1 and daily oral UFT 350 mg/m2 in 3 divided doses for 21 days and repeated every 21 days. Thirty-one of 34 patients were assessable for response and 32 patients for toxicity. Partial response was observed in four patients and stable disease in six patients. The response rate was 12.9% (95% CI, 3.6-29.8%) and median duration of response was 17 weeks. The median overall survival and progression-free survival of all patients were 26 weeks (range, 3-90+ weeks) and 9 weeks (range, 3-56 weeks), respectively. Sensory neuropathy was the most common toxicity, but there was no severe toxicity (>grade II) except for a case of grade III neutropenia. We conclude that oxaliplatin and UFT combination chemotherapy was well tolerated without significant toxicities. The results of this trial will serve as the basis for designing new clinical trials with a different dose or schedule.

Self-expandable covered metallic esophageal stent impregnated with beta-emitting radionuclide: an experimental study in canine esophagus.

PURPOSE: A specially designed self-expandable covered metallic stent impregnated with the beta-emitting radioisotope 166Ho (166Ho, energy: 1.85 and 1.76 MeV, T12: 26.8 h) was developed at our institute for the purpose of intraluminal palliative brachytherapy, as well as for treating malignant esophageal stricture and swallowing difficulty. The aim of this study was to evaluate the tissue response to brachytherapy and the safety of the radioactive metallic stent with regard to the normal canine esophagus before clinical application. METHODS AND MATERIALS: 166Ho was impregnated into the polyurethane membrane (50 micron thickness) covering the outer surface of a self-expandable metallic stent (diameter, 18 mm; length, 40 mm). Stents with radioactivity 4.0-7.8 mCi (Group A, n = 15), 1.0-1.8 mCi (Group B, n = 5), and 0.5-0.7 mCi (Group C, n = 5) were placed in the esophagi of 25 healthy beagle dogs, and the stents were tightly anchored surgically to prevent migration. The estimated radiation dose calculated by Monte Carlo simulation was 194-383 Gy in Group A, 48-90 Gy in Group B, and 23-32 Gy in Group C. The dogs were killed 8-12 weeks after insertion of the stents, and histologic examinations of the esophageal walls were performed. RESULTS: In Group A, 3 of 15 dogs died of wound infection, so specimens were obtained from only 12 dogs; all 12 cases showed esophageal stricture with mucosal ulceration. Microscopically, severe fibrosis and degeneration of the muscular propria were found in 3 dogs, complete fibrosis of the entire esophageal wall was found in 7 dogs, and esophageal fibrosis with radiation damage within periesophageal soft tissue was found in 2 dogs. However, esophageal perforation did not develop, despite extremely high radiation doses. In Group B, glandular atrophy and submucosal fibrosis were found, but the muscular layer was intact. In Group C, no histologic change was found in 3 dogs, but submucosal inflammation and glandular atrophy with intact mucosa were found in 2 dogs. CONCLUSIONS: A radioactive, self-expandable covered metallic stent can be used as an alternative therapeutic modality for the palliative treatment of malignant esophageal stricture.

An unusual case of osteoblastic metastasis from gastric carcinoma.

We report an unusual case of osteoblastic metastasis from gastric carcinoma. In this case, bone metastasis was the initial manifestation of the cancer. The laboratory findings revealed mild hypocalcemia and markedly elevated alkaline phosphatase levels. Plain X-ray showed mottled osteoblastic changes in the pelvis. Bone marrow and bone biopsy of the pelvis revealed metastatic adenocarcinoma with increased osteoblastic activity. An extensive search for the primary site revealed advanced gastric carcinoma, which was confirmed by endoscopic biopsy.