Treatments and prognostic factors for bone and soft tissue sarcoma in non-urban areas in Japan.

BACKGROUND: Although bone and soft tissue sarcoma is recognized as a rare cancer that originates throughout the body, few comprehensive reports regarding it have been published in Japan. PATIENTS AND METHODS: Bone and soft tissue sarcomas were tabulated from the Cancer Registries at eight university hospitals in the Chugoku-Shikoku region. Prognostic factors in cases were extracted in a single facility and have been analyzed. RESULTS: From 2016 to 2019, 3.4 patients with bone and soft tissue sarcomas per a general population of 100,000 were treated at eight university hospitals. The number of patients who underwent multidisciplinary treatment involving collaboration among multiple clinical departments has been increasing recently. In the analysis carried out at a single institute (Ehime University Hospital), a total of 127 patients (male/female: 54/73) with an average age of 67.0 y (median 69.5) were treated for four years, with a 5-year survival rate of 55.0%. In the analysis of prognostic factors by multivariate, disease stage and its relative treatment, renal function (creatinine), and a patient's ability of self-judgment, and a patient's mobility and physical capability were associated with patient prognosis regarding bone and soft tissue sarcomas. Interestingly, age did not affect the patient's prognosis (> 70 vs ≦ 70). CONCLUSIONS: Physical and social factors may affect the prognosis of patients with bone and soft tissue sarcomas, especially those living in non-urban areas.

The prognostic significance of whole-body and spleen MTV (metabolic tumor volume) scanning for patients with diffuse large B cell lymphoma.

BACKGROUND: Positron Emission Tomography-Computed Tomography (PET-CT) has been changing diagnostic and therapeutic strategies for patients with cancers, and several PET-CT-related prognostic factors have been reported. We have focused on metabolic tumor volumes (MTVs) over the whole body and in specific organs using 18F-PET-CT imaging, and have compared clinical data to know the prognosis of patients with diffuse large B cell lymphoma (DLBCL). PATIENTS AND METHODS: From January 2006 to December 2016, patients who were newly diagnosed for de novo DLBCL and who received 18F-FDG PET-CT scans for disease staging at Ehime University Hospital were reviewed. RESULTS: A total of forty out of 108 patients with DLBCL were analyzed. The median and the average follow-up were 3.9 years and 3.6 years. Both MTV50 and MTV60 whole-body searching indicated effective prognostic values for patients with DLBCL statistically (P = 0.027). However, analysis of MTVs in the spleen and in bone marrow did not provide any prognostic value. Receiver operating characteristic (ROC) analysis indicated that the cutoff level 25.8 in MTV60 is the most effective prognostic value (P = 0.022) which predicts patient survival after treatment with R-CHOP chemotherapy. CONCLUSION: MTV60 using whole-body scanning appears to be an effective indicator in DLBCL and indicates the patient prognosis.

Severe refractory infection due to renocolic fistula in a patient with a giant kidney and ADPKD undergoing long-term hemodialysis.

Renocolic fistula is rare. Renal cyst infection is a serious complication in patients with autosomal dominant polycystic kidney disease (ADPKD). We present a case of refractory renal cyst infection due to renocolic fistula in a patient with ADPKD. A 65-year-old man with ADPKD on hemodialysis visited our hospital with complaints of fever and left abdominal pain. We diagnosed renal cyst infection with abdominal computed tomography scans. After hospitalization, gas shadow was observed in the left renal cyst. Percutaneous puncture of the cyst was performed. Because contrast medium into the left renal cyst through nephrostomy was flowing into the descending colon, renocolic fistula was diagnosed. The patient underwent nephrectomy combined with partial descending colonic resection and splenectomy, but he died. Renocolic fistula is probably hidden in some refractory renal cyst infection cases. This case report aims to create awareness of renocolic fistula, so that early diagnosis and intervention can salvage such patients.

Expression and localization of fibroblast growth factor (FGF)23 and Klotho in the spleen: its physiological and functional implications.

The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220+ CD21/CD35+ CD1d+ CD43- marginal zone B cells. These cells also expressed FGF receptor 1, indicating that Klotho-positive B cells could respond to FGF23. Plasmacytoid dendritic cells (pDCs) with CD11c+ CD45R/B220+ CD11b- CD8α- were found to produce FGF23. Klotho-positive cells and FGF23-producing cells were present in close proximity to each other, suggesting that FGF23 produced by pDCs may act within a limited area. These findings indicate that FGF23-Klotho signaling could play a biological or immunological role in the spleen.

Effects of Cyclophosphamide Pulse Therapy on the Clinical and Histopathological Findings, Particularly Crescent Formation, in a Patient with Adult-onset Steroid-refractory Henoch-Schönlein Purpura Nephritis.

A 29-year-old woman was diagnosed with Henoch-Schönlein purpura nephritis (HSPN) based on the presence of purpura and histopathological findings showing crescent formation, mesangial proliferation and IgA deposition in the glomerular mesangium. She was treated with high-dose steroids; however, the nephritic syndrome persisted. Therefore, we diagnosed her with steroid-resistant HSPN and decided to add treatment with cyclosphamide pulse therapy. After one year of treatment, the histopathological findings, including crescent formation and IgA deposition, improved, as confirmed on a renal biopsy, and the patient fulfilled the criteria for complete remission. Cyclophosphamide pulse therapy may be considered an effective treatment for intractable HSPN.

Safety and efficacy evaluation of lanthanum carbonate for hyperphosphatemia in end-stage renal disease patients.

In end-stage renal disease patients, various abnormalities of bone mineral metabolism adversely affect mortality. Hyperphosphatemia is known to adversely affect mortality and quality of life in chronic kidney disease patients and has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. Thus, hyperphosphatemia is the main treatment target indicated in several guidelines for chronic kidney disease-mineral and bone disorder treatment. Phosphate binders are typically required for the management of hyperphosphatemia because dietary phosphorus restriction and phosphorus removal by hemodialysis alone are insufficient. We are able to prescribe five phosphate binders (calcium carbonate, sevelamer HCl, lanthanum carbonate (LaC), bixalomer, and ferric citrate) to Japanese hemodialysis patients. LaC is the most powerful noncalcium-containing phosphate binder for the treatment of hyperphosphatemia. In this chapter, we discuss the efficacy and safety of LaC, the safety of which has been under debate. In particular, we consider its toxic effects on the skeletal system. LaC is effective for hyperphosphatemia treatment in end-stage renal failure patients. It has been shown to be able to decrease serum fibroblast growth factor-23 levels. This result suggests that it may have beneficial effects on the cardiovascular system in patients undergoing renal replacement therapy. However, the effects of LaC remain obscure. Further investigations are required. No negative effects of LaC on bone metabolism or bone morphometry have been reported, but long-term clinical data are needed.

Alendronate as an effective treatment for bone loss and vascular calcification in kidney transplant recipients.

Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication, with a high risk of fracture, and abdominal aortic calcification (AC) is a known predictor of cardiovascular mortality. In this study of 12 stable kidney recipients, we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC. We randomly divided the subjects into a treatment group with alendronate (group A: 5 subjects) and a control group (group C: 7 subjects). Group A patients received 35 mg/week of alendronate over 24 months, while group C patients were not administered with any bisphosphonates. Two major endpoints were established: (1) the time-dependent change in bone mineral density (BMD) estimated with DEXA and (2) progression of abdominal AC, calculated twice as an index (ACI) using computed tomography data. Over the 2-year study period, group A patients showed significantly increased BMD of 1.86 ± 0.85% (P = 0.015 versus baseline), and almost complete inhibition of ACI progression (38.2 ± 24.2% to 39.6 ± 24.3%), but group C patients showed a decrease in BMD decline with bone loss and progression of ACI (32.8 ± 25.0% to 37.8 ± 29.2%, P = 0.061). In conclusion, alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification. This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR.

Tonsillectomy with steroid pulse therapy has more effect on the relapse rate than steroid pulse monotherapy in IgA nephropathy patients.

AIMS: Both steroid pulse (SP) monotherapy and the combination of tonsillectomy and SP therapy (TSP) are effective for achieving clinical remission (CR), defined as negative hematuria and proteinuria, in patients with IgA nephropathy (IgAN). The role of tonsillectomy in the treatment of IgAN has been analyzed only from the aspect of CR or renal survival after TSP treatment, so there is no evidence of its effect on the relapse after CR. METHODS: We retrospectively investigated relapse (re-appearance of urinary abnormalities) from CR after TSP or SP monotherapy in 62 IgAN patients (mean follow-up, 70.1 ± 35.3 months). The SP therapy comprised 0.5 g methylprednisolone administered intravenously on 3 consecutive days followed by oral prednisolone (30 mg/day) on 4 consecutive days, with the course repeated 3 times. Oral prednisolone (30 mg/day) was then given on alternative days and gradually tapered and finished over 1 year. Tonsillectomy was performed either before or within 6 months of starting SP therapy. RESULTS: At baseline, the mean age was 34.6 years, the mean serum creatinine (Cr) level was 0.9 mg/dl, and the mean level of proteinuria was 876 mg/day. There were no differences between the TSP group (41 patients) and SP monotherapy group (21 patients). In total, 24 of the TSP and 10 of the SP patients achieved CR. Of the 34 patients who achieved CR, 13 relapsed after TSP or SP monotherapy. Using Kaplan-Meier analysis, tonsillectomy was associated with a lower incidence of relapse from CR after treatment (p = 0.045). Multivariate Cox regression analysis revealed that tonsillectomy reduced the rate of from CR after SP therapy. CONCLUSION: Tonsillectomy was associated with a reduction in the relapse rate from CR after SP therapy in IgAN patients.

[Newly development of phosphate binders in hyperphosphatemic patients with kidney dysfunction].

Hyperphosphatemia is the most common complication among patients with chronic kidney disease. Large scale observational studies have identified hyperphosphatemia as an independent risk factor for cardiovascular disease and mortality in hemodialysis patients. The combination therapy of dietary phosphate restriction and phosphate removal with dialysis treatment is still not enough to achieve the serum phosphate within the target. Thererfore, phosphate binders is necessary for many dialyzed patients with hyperphosphatemia. In this article, we will review the detail and development of phosphate binders and recommendation for clinical practice in hyperphosphatemia.

The management of hyperphosphatemia by lanthanum carbonate in chronic kidney disease patients.

Hyperphosphatemia has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. In addition, it influences the clinical course of patients with chronic kidney disease. Phosphate (Pi) binder is required in the management of hyperparaphosphatemia, because dietary Pi restriction and Pi removal by hemodialysis alone are insufficient. Lanthanum carbonate, a powerful Pi binder, has a similar effect to aluminum hydroxide in reducing serum Pi levels. As it is excreted via the liver, lanthanum carbonate has an advantage in patients with renal failure. The effect of lanthanum carbonate on serum Pi levels is almost two times higher than that of calcium (Ca) carbonate, which is commonly used. Lanthanum carbonate and Ca carbonate have an additive effect. Worldwide, there is 6 years worth of clinical treatment data on lanthanum carbonate; however, we have 3 years of clinical use in Japanese patients with hyperphosphatemia. No serious side effects have been reported. However, the most important concern is bone toxicity, which has been observed with use of aluminum hydroxide. For this study, clinical research involved analysis of bone biopsies. Although osteomalacia is the most noticeable side effect, this was not observed. Both the high- and the low-turnover bone disease concentrated into a normal bone turnover state. However, as the authors have less than 10 years' clinical experience with lanthanum carbonate, patients should be monitored carefully. In addition, it is necessary to demonstrate whether potent treatment effects on hyperphosphatemia improve the long-term outcome.

[Secondary osteoporosis UPDATE. Therapy for bone-mineral disease in CKD-5D patients].

Recently, much of the attention given to bone-mineral disorder as the prognostic factor for mortality has focused on their links to chronic kidney disease (CKD-MBD; chronic kidney disease-mineral bone disease), especially in dialysis patients. Bone disease in dialysis patients showed heterogeneity caused by multiple factors other than postmenopausal osteoporosis. Evaluation of the bone mineral density with DEXA and the bone metabolic markers becomes useless for the assessment of bone fragility in dialysis patients. Prevalence of bone fracture in end-stage renal disease patients is 3-4 times higher than that in general population. The skeletal fracture in ESRD patients is suggested to be related with malnutrition. Guidelines of the therapy for bone-mineral disorder in dialysis patients is centered on the prevention of cardio-vascular disease and the mortality. Physicians should carefully understand these effects in the daily clinical practices.