Comparing bone resorption after anatomical shoulder arthroplasty between various surgical procedures using a single-stem model

BackgroundIn shoulder arthroplasty, bone resorption around the stem can lead to stem loosening and makes surgery difficult at the time of revision. Proximal bone resorption after reverse shoulder arthroplasty can cause instability because of a decrease of deltoid wrapping effect. As factors of the stem itself, such as stem coating, shape, length, and use of bone cement, may also affect bone resorption, a single-stem model should be used to compare bone resorptions between different pathologies and surgical procedures. However, to date, a few reports have compared these differences in detail using a single-stem model. Therefore, we investigated the prevalence and location of humeral bone resorption in a single-stem model.MethodsThe study included 100 shoulders that underwent anatomical total shoulder arthroplasty (TSA) or humeral head replacement (HHR) with a single uncemented humeral stem from 2008 to 2018. The patients were 31 men and 69 women. The mean age at surgery was 72.9 years (range, 41-86 years). The patients were divided into three groups: especially, 25, 61, and 14 shoulders received TSA for primary osteoarthritis without rotator cuff tears (TSA group), HHR using an anatomical head with rotator cuff repair for cuff tear arthropathy (CTA) (HHR group), and HHR using a CTA head without rotator cuff repair (CTA group), respectively. Patients were monitored for a mean of 56 months (range, 12-98 months). The location of bone resorption was divided into seven zones as follows: zone 1, greater tuberosity; zone 2, lateral diaphysis; zone 3, lateral diaphysis beyond the deltoid tuberosity; zone 4, tip of the stem; zone 5, medial diaphysis beyond the deltoid tuberosity; zone 6, medial diaphysis; and zone 7, calcar region. The degree of bone resorption was classified from grade 0 to 4.ResultsBone resorption of grade 3 or higher was significantly more frequent at the greater tuberosity in the HHR and CTA groups (P < .001 and P < .001, respectively) than that in the TSA group. Grade 4 bone resorption was significantly more frequent in the CTA than that in the TSA and HHR groups in zone 1 (P = .016 and P = .041, respectively).ConclusionThe state of attachment of the rotator cuff to the greater tuberosity might affect bone resorption at the greater tuberosity, such as the greater tuberosity after shoulder arthroplasty. In cases of shoulder arthroplasty for arthropathy with rotator cuff tear, performing rotator cuff repair might prevent bone resorption.Level of evidenceLevel IV; Prognosis Study     

E‐cadherin‐Fc chimera protein matrix enhances cancer stem‐like properties and induces mesenchymal features in colon cancer cells

Cancer stem cells (CSC) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of CSC is essential for developing cancer therapies, scarcity of the CSC population has hindered such analyses. The aim of the present study was to elucidate whether the E‐cadherin‐Fc chimera protein (E‐cad‐Fc) enhances cancer stem‐like properties because studies show that soluble E‐cadherin stimulates human epithelial growth factor receptor (EGFR) and downstream signaling pathways that are reported to play a crucial role in CSC. For this purpose, we used ornithine decarboxylase (ODC)‐degron–transduced (Degron(+)) KM12SM cells as a CSC model that retains relatively low CSC properties. Compared to cultures without E‐cad‐Fc treatment, we found that E‐cad‐Fc treatment further suppressed proteasome activity and largely enhanced cancer stem‐like properties of ODC‐degron–transduced KM12SM cells. These results include increased expression of stem cell markers Lgr5, Bmi‐1, SOX9, CD44, and CD44v9, aldehyde dehydrogenase (ALDH), and enhancement of robust spheroid formation, and chemoresistance to 5‐fluorouracil (5‐FU) and oxaliplatin (L‐OHP). These effects could be attributed to activation of the EGFR pathway as identified by extensive phosphorylation of EGFR, ERK, PI3K, AKT, and mTOR. In SW480 cells, E‐cad‐Fc matrix induced some CSC markers such as CD44v9 and ALDH. We also found that E‐cad‐Fc matrix showed high efficiency of inducing mesenchymal changes in colon cancer cells. Our data suggest that the E‐cad‐Fc matrix may enhance CSC properties such as enhancement of chemoresistance and sphere formation.     

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

This first‐in‐man study was carried out to evaluate the safety, whole‐body distribution, dose estimation, and lesion accumulation of ¹⁸F‐FSU‐880, a newly developed probe targeting prostate‐specific membrane antigen. Six prostate cancer patients with known metastatic lesions underwent serial whole‐body PET/computed tomography (CT) with ¹⁸F‐FSU‐880. Blood and urine were analyzed before and after PET/CT. Accumulation of ¹⁸F‐FSU‐880 in organs and metastatic lesions in serial PET images were evaluated by measuring the standardized uptake values. From the biodistribution data, the organ doses and whole‐body effective dose were calculated using OLINDA/EXM software was developed by Dr. Michael Stabin of Vanderbilt University, Nashville, Tennessee, USA. ¹⁸F‐FSU‐880 PET/CT could be carried out without significant adverse effects. High physiological uptake was observed in the salivary/lachrymal glands and kidneys. The effective dose was calculated to be 0.921 × 10^?2 mSv/MBq. Known metastatic lesions were clearly visualized with high image contrast that increased with time, except in 1 patient, whose bone metastases were well‐controlled and inactive. The PET/CT with ¹⁸F‐FSU‐880 could be carried out safely and could clearly visualize active metastatic lesions. The present results warrant further clinical studies with a larger number of cases to verify the clinical utility of ¹⁸F‐FSU‐880 PET/CT in the management of prostate cancer patients.     

Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer

IntroductionCarboplatin and paclitaxel (CP) had shown moderate efficacy in treating castration-resistant prostate cancer (CRPC) before standard first-line docetaxel chemotherapy became available. Currently, for patients with homology-directed repair gene defects as well as for unselected patients, platinum chemotherapy is administered after all standard treatments have been ineffective. Here, we retrospectively studied the efficacy and safety of CP administered as the first-, second-, and third-line chemotherapy in patients with CRPC.Patients and MethodsA retrospective chart review was performed for 58 patients with CRPC who received CP between 2001 and 2018 in a single institution. Twenty-seven patients received CP as the first-line chemotherapy, 21 as the second-line after docetaxel, and 10 as the third-line after docetaxel and cabazitaxel. Prostate-specific antigen (PSA) responses (> 50% decline of PSA from baseline), progression-free survival, overall survival, and adverse events were examined.ResultsPSA responses at any time were 55.6%, 19.0%, and 10.0%; PSA responses at 12 weeks were 48.1%, 14.3%, and 10.0%; the median progression-free survival was 3, 1, and 1 month; and the median overall survival was 19, 11, and 6 months, respectively, for the first-, second-, and third-line settings. The only patient who achieved exceptional and durable PSA response in the third-line setting had a deleterious germline BRCA2 mutation (5645C>A). The adverse event profile was favorable.ConclusionCP shows moderate efficacy against CRPC in the first-line setting, but shows little effect in the third-line setting. CP after docetaxel and cabazitaxel may be recommended in selected patients with CRPC with homology-directed repair gene defects.     

Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia

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Differences in treatment and survival between elderly patients with thoracic esophageal cancer in metropolitan areas and other areas

To address the major issue of regional disparity in the treatment for elderly cancer patients in an aging society, we compared the treatment strategies used for elderly patients with thoracic esophageal cancer and their survival outcomes in metropolitan areas and other regions. Using the national database of hospital-based cancer registries in 2008-2011, patients aged 75 years or older who had been diagnosed with thoracic esophageal cancer were enrolled. We divided the patients into two groups: those treated in metropolitan areas (Tokyo, Kanagawa, Osaka, Aichi, Saitama, and Chiba prefectures) with populations of 6 million or more and those treated in other areas (the other 41 prefectures). Compared were patient backgrounds, treatment strategies, and survival curves at each cancer stage. In total, 1236 (24%) patients from metropolitan areas and 3830 (76%) patients from nonmetropolitan areas were enrolled. Patients in metropolitan areas were treated at more advanced stages. There was also a difference in treatment strategy. The 3-year survival rate among cStage I patients was better in metropolitan areas (71.6% vs. 63.7%), and this finding mainly reflected the survival difference between patients treated with radiotherapy alone. For cStage II-IV patients, there were no differences. Multivariable Cox proportional hazard analysis including interaction terms between treatment areas, cStage, and the first-line treatments revealed that treatments in the metropolitan areas were significantly associated with better survival among patients treated with radiotherapy alone for cStage I cancer. Treatment strategies for elderly patients with thoracic esophageal cancer and its survival outcomes differed between metropolitan areas and other regions.