Derotational Hybrid Closed-Wedge High Tibial Osteotomy for Knee Osteoarthritis With Patellar Subluxation Caused by Tibial Torsional Deformity.

Patellar subluxation and recurrent dislocation are commonly treated with medial patellofemoral ligament reconstruction, and patients with predisposing factors for these problems often require additional bony realignment procedures. However, these procedures mainly address problems in the axial plane, and patients with medial-compartmental knee osteoarthritis may require further realignment in the coronal plane. In this Technical Note article, we introduce our technique for derotational hybrid closed-wedge high tibial osteotomy. Using this technique, simultaneous 3-dimensional realignment in the axial, coronal, and sagittal planes can be achieved in patients with medial compartmental knee osteoarthritis and patellar subluxation caused by a tibial torsional deformity. The indications for the technique and the preoperative planning assessments involving a static torsional deformity analysis on computed tomography images and a dynamic gait analysis by our walking-on-paper method are presented. This is followed by a detailed description of the surgical procedure, together with consideration of the pearls and pitfalls of the procedure. A video of the surgery performed in a representative case with medial knee osteoarthritis and patellar subluxation in the right knee owing to an outward tibial torsion deformity is also provided.

Double-Row Root Repair with Bridging Centralization Using Double Nonsliding Anchors for Medial Meniscus Posterior Root Tear.

Medial meniscal posterior root tears disrupt the "hoop" function of the meniscus and may lead to knee osteoarthritis. Although root repair could be a key to osteoarthritis prevention, this surgery does not necessarily guarantee an optimal result even when combined with meniscal centralization and high tibial osteotomy. To address this issue, we made five modifications to the original combined approach, namely two anchors to fix the root, instead of one; bridging centralization instead of single centralization; release of the meniscotibial capsule vs no release; release of valgus stress before knot tying vs no release; and prohibiting postoperative cross-legged sitting and sitting on heels. The advantages of this approach over the original approach are numerous and comprise ease of performing concurrent open wedge high tibial osteotomy, shorter fixation distance, better anatomical reattachment of the meniscal root, increased bone-meniscus contact and contact pressure, and larger contact area between the capsule and tibial rim. The disadvantages of the approach are that knot-tying is cumbersome, pie-crusting of the medial collateral ligament is necessary in patients not undergoing open wedge high tibial osteotomy, and tears >3 mm from the attachment are a contraindication. We describe the steps in this modified approach in detail.

Flexion Contracture in Knee Osteoarthritis Can Be Fully Eliminated by Hybrid Closed Wedge High Tibial Osteotomy Using a Reduction-Insertion-Compression Handle.

In conventional closed-wedge high tibial osteotomy (CWHTO) with preservation of the medial hinge, flexion contracture cannot be improved because of the two-dimensional correction. Conversely, in hybrid CWHTO, for which the name is derived from a hybrid of the lateral closing and medial opening, the medial cortex is intentionally disrupted. The medial hinge disruption enables three-dimensional correction, which helps eliminate flexion contracture by decreasing posterior tibial slope (PTS). The fine adjustment of the anterior closing distance and thigh-compression technique further facilitates PTS control. In this study, we describe the use of the Reduction-Insertion-Compression Handle (RICH), which maximizes the benefits of hybrid CWHTO. This device permits accurate osteotomy reduction, easy screw insertion, and assists with providing sufficient compressive force at the osteotomy site, as well as the elimination of the flexion contracture. This Technical Note presents the details of using the RICH and the associated advantages and disadvantages in hybrid CWHTO for medial compartmental knee arthritis.

Femoral-varus tibial-valgus osteotomy (FVTVO) for neutrally-aligned knee osteoarthritis with severe joint line obliquity enables return to sports activities: A case series study.

Background: Re-alignment surgeries for uni-compartmental knee osteoarthritis, such as high tibial osteotomy (HTO) for varus knees or distal femoral osteotomy (DFO) for valgus knees, are recognized as standard strategies. However, the treatment strategy has not been established for patients with a neutrally-aligned osteoarthritic knee with severe joint line obliquity (JLO) owing to the combination of a valgus femur and a varus tibia; i.e., type II coronal plane alignment of the knee (CPAK). total knee arthroplasty (TKA) can be an option for CPAK type II-aligned osteoarthritis in older inactive patients. Here, we hypothesized that joint line horizontalization by femoral-varus tibial-valgus osteotomy (FVTVO), which may reduce the shear stress induced by JLO, could be a treatment option for CPAK type II-aligned osteoarthritis in young active patients who wish to return to sports (RTS) activity. Our aim in this study was to evaluate the postoperative results of FVTVO with RTS. Methods: Our indications for FVTVO are as follows: JLO >5°; mechanical medial proximal tibial angle (mMPTA) < 87°; mechanical lateral distal femoral angle (mLDFA) < 87°; typical osteoarthritis patterns for CPAK type II on magnetic resonance images, namely osteoarthritic change of the lateral tibial spine, medial slip of the femur, and/or lateral meniscal extrusion from the lateral femoral condyle; and flexion contracture <10°. We enrolled patients who wished to RTS and who had a pre-symptom Tegner score ≥5 and had completed at least a 1-year follow-up. For FVTVO, closed-wedge DFO was performed in all femurs; both closed-wedge HTO and open-wedge HTO were used in the tibia, depending on the situation. Range of motion exercises began on the first postoperative day, and full weight-bearing was permitted 6 weeks postoperatively. Jogging was permitted 3 months postoperatively after confirming bone union, and patients could gradually return to their sports activity 6-12 months' postoperatively. The Japanese Orthopaedic Association (JOA) score and knee flexion range were assessed preoperatively and at the last follow-up. Tegner activity scale scores were assessed presymptom, preoperatively, and at the last follow-up. The hip-knee-ankle (HKA) angle, JLO, mMPTA, and mLDFA were evaluated radiologically, and meniscal extrusions, osteoarthritic change, and/or bone marrow edema were assessed on magnetic resonance images. Results: One man and two women were included in this case series. Two were competitive athletes and one was a mountain climber. The patients' ages were 69, 46, and 57 years (Case 1, 2, and 3, respectively). All patients' CPAK type was converted from type II to type V; i.e., neutral-aligned knee with a neutral joint line, postoperatively. All patients returned to their presymptom sports activity level by the final follow-up. The presymptom/preoperative/final follow-up Tegner scale in Case 1, 2, and 3 were 6/1/6, 5/2/5, and 7/3/7, respectively. Conclusion: Joint line horizontalization by FVTVO for patients with a neutral-aligned knee with severe JLO provided highly satisfactory clinical results and successfully led to RTS.

Anteromedial plating without filling the gap in open wedge high tibial osteotomy may increase the risk of screw breakage, which can be reduced by medial plating and bone-substitute insertion.

BACKGROUND: Open wedge high tibial osteotomy (OWHTO) brings new complications such as screw breakages with or without correction loss and time-dependent increased posterior tibial slopes (PTS) due to the opening gap. For preventive purposes, we changed our OWHTO procedure from anteromedial plating without filling the gap (non-grafted group, n = 40, 2009-2012) to medial plating with bone-substitute insertion (grafted group, n = 45, 2012-2015). The objectives of this study were to evaluate the complication patterns and the effects of the modifications. METHODS: Patients undergoing OWHTO with TomoFix plates were included in this retrospective study. Demographics, clinical outcomes (flexion range and Japanese Orthopaedic Association score) and radiological outcomes (femorotibial angle) were assessed in both groups pre-operatively and 2-years postoperatively. The plate installation angle [PIA] and screw insertion depth [SID] were measured on computed tomographic slices at 6 months. PIA/SID was defined as the angle between the tibial anteroposterior axis and plate-width axis/the distance between the proximal screw tip and the proximal tibiofibular joint. The non-grafted group was further divided into complication and non-complication subgroups. Screw breakages were assessed during plate removal (1.5-2.5 years postoperatively). RESULTS: There were no differences in baseline characteristics or radiological/clinical outcomes between the non-grafted and grafted groups. There were 0 and 11 complications in the grafted and non-grafted groups, respectively. Complications included 7 screw breakages, 4 correction losses, and 5 time-dependent increased PTS with some overlaps. PIA and SID were significantly lower (p < 0.001) and higher (p < 0.001), respectively, in the grafted group and significantly lower (p = 0.018) and higher (p = 0.040), respectively, in the non-complication subgroup within the non-grafted group. The cutoff value of PIA for complications was calculated at 48.0°. CONCLUSIONS: Medial plating OWHTO (PIA<48°) using bone-substitute with deeper screw insertion reinforces the opening gap for better angular stability compared with anteromedial plating without bone-substitute.

Around-knee osteotomy conversion for failed high tibial osteotomy: Re-correction high tibial osteotomy and additional distal femoral osteotomy may enable return to sporting activities.

High tibial osteotomy (HTO) for knee osteoarthritis achieves excellent short- and long-term results. However, failure of HTO due to undercorrection or correction loss may necessitate conversion surgery. For patients with HTO failure who desire a return to sporting activities (RTS), non-prosthetic joint-preserving solutions such as conversion to around-knee osteotomies (AKO-conversion) may be more appropriate than total knee arthroplasty. The present study aimed to introduce potential non-prosthetic joint-preserving solutions for failed HTO and investigate the postoperative RTS. Among the patients who received non-prosthetic solutions for failed HTO from 2015 to 2020, this case series included those who were eager to RTS, were participating in a sporting activity with a Tegner activity scale score of ≥5 immediately before being affected by knee osteoarthritis, and had at least 2 years of follow-up. Deformity analysis for the preoperative planning of the AKO-conversion was based on the mechanical lateral distal femoral angle, joint line convergence angle, and mechanical medial proximal tibial angle. Four patients met the study inclusion criteria: two patients who underwent re-correction HTO and two who received additional distal femoral osteotomy (DFO). The average ages at primary HTO and AKO-conversion were 69.5 ± 11.8 years and 71.5 ± 10.9 years, respectively. The hip-knee-ankle angle was corrected from -2.8 ± 1.5° before conversion surgery to 3.3 ± 1.5° at 2 years after AKO-conversion. All four patients finally achieved a better sporting performance after AKO-conversion than preoperatively, and the Tegner activity scale score was improved from 2.5 ± 1.0 before AKO-conversion to 5.8 ± 0.5 at the 2-year follow-up. The duration between AKO-conversion and full RTS was 11.8 ± 6.7 months. In conclusion, two patients who underwent re-correction HTO and two who underwent additional DFO for undercorrection or correction loss after primary HTO achieved highly satisfactory clinical results, including RTS. The present findings suggest that non-prosthetic joint-preserving solutions using AKO for failed HTO should be considered as options to enable RTS.

Ankle-Angle-Adjusting Fibular Osteotomy in Closed Wedge High Tibial Osteotomy.

Closed-wedge high tibial osteotomy (CWHTO) may be carried out to realign the knee in patients with knee osteoarthritis who do not meet the criteria for open-wedge high tibial osteotomy or total knee arthroplasty. The procedure involves both fibular and tibial osteotomy, and care is needed to prevent peroneal nerve and vessel injury during fibular osteotomy. Notably, use of a tourniquet may mask the development of hematomas or aneurysms until after surgery. We developed a 3-step ankle-angle-adjusting (triple-A) technique to relax the muscles, allowing easy retraction of the peroneal vessels. Crucially, the procedure does not require a tourniquet, thus allowing bleeding to be detected and stopped during surgery. The process involves adjusting the ankle angle by plantar-flexion and applying varus stress to highlight the tension difference between the lateral and posterior compartments; plantar-flexion of the great toe to loosen the flexor hallucis longus muscle, thus exposing the fibular posterior aspect; and valgus stress to loosen the peroneus longus muscle. The muscles can then be retracted sufficiently to allow distal and proximal osteotomies to be performed, and any bleeding can be detected and resolved before wound closure. This technique may improve the ease and safety of fibular osteotomy in patients undergoing CWHTO.

A spreading roots sign: Characteristic sign of the preliminary stage of medial meniscus posterior root tear on magnetic resonance imaging.

BACKGROUND: Medial meniscus posterior root tears (MMPRTs) can result in the development of osteoarthritis or osteonecrosis. Clinical experience suggests that symptoms such as dull pain or discomfort in the popliteal area or the calf area, which are sometimes misdiagnosed as sciatic nerve pain, may precede impending rupture. We found that bone marrow edema emanating from the meniscal root on magnetic resonance imaging (MRI) scans-spreading roots sign-may indicate the preliminary stage of an MMPRT. The purpose of this study was to evaluate the efficacy of the spreading roots sign as an MMPRT-predictor. METHODS: In a retrospective study, we reviewed the chart data and MRI results of patients who had required surgery for an acute MMPRT. We grouped patients by whether or not they had reported the above-mentioned precursory symptoms prior to acute rupture (precursory symptom group/non-precursor group), and when possible, we examined MRI scans to identify with which events the appearance/disappearance of the spreading roots sign coincided. Sex, age, body mass index, bone mineral density, radiological parameters, and MRI parameters were compared between groups. RESULTS: Data from 24 patients (precursory symptom group, n = 17 [70.8 %]; non-precursor group, n = 7 [29.2 %]) were included; data from 5 patients included MRI scans prior to acute rupture. There were no significant differences between precursory symptom and non-precursor groups, except for the ratio of the presence of the spreading roots sign (p = 0.005). The appearance of the spreading roots sign on MRI scans coincided with the onset of precursory symptoms, and its disappearance coincided with acute rupture and the appearance of other MRI signs typical of MMPRT (white meniscus/truncation/meniscal extrusion/giraffe neck signs). CONCLUSIONS: Our findings suggest that the spreading roots sign can be used as a unique precursory sign for MMPRT.

Factors Associated with Dose Modification of Lenalidomide Plus Dexamethasone Therapy in Multiple Myeloma.

Long-term combination treatment with lenalidomide and low-dose dexamethasone is important to achieve a curative effect in patients with multiple myeloma (MM). In this study, the plasma concentration of lenalidomide was measured at 3 h after oral administration, when the drug is in the elimination phase and can be easily measured in outpatients, to identify factors that may lead to the discontinuation of this combination therapy. Patients were assigned to continuation or discontinuation of therapy groups, and the baseline characteristics of patients, lenalidomide concentration, and concentration/dose (C/D) ratios reflecting oral clearance were compared between the two groups. The efficacy and severity of adverse events were also compared. The results showed that patients who discontinued or modified treatment had low plasma concentrations of lenalidomide and C/D ratios, indicating high oral clearance of lenalidomide. The estimated creatinine clearance rate was negatively correlated with the C/D ratio. The plasma concentrations of lenalidomide were independent from kidney function and differed significantly among patients. Taken together, the results indicate that low plasma concentrations of lenalidomide and low C/D ratios may lead to discontinuation of combination therapy in patients with MM. This suggests that early measurement of lenalidomide plasma continuation would help to prevent discontinuation of therapy or a delay in modifying the dose of lenalidomide.

A retrospective analysis of treatment outcomes in 45 patients with cardiac light-chain amyloidosis: a single-center experience in Japan.

The prognosis of cardiac light-chain (AL) amyloidosis is considered to be very poor. We studied the treatment efficacy and outcomes by retrospectively analyzing the clinical results of 45 patients with cardiac AL amyloidosis treated at our hospital between September 2008 and March 2016. The group of patients analyzed included 29 males and 16 females with a median age of 68 years. Their baseline median NT-proBNP, cTnT, and dFLC were 3167 pg/ml, 0.080 ng/ml, and 286.17 mg/l, respectively. Twenty-eight patients were in Cardiac Stage (CS) III and 17 patients were in Revised Prognostic Stage (RPS) IV. At the median follow-up of 10 months, the median overall survival (OS) was 16 months and 3-year OS was 35.9%. The patients in CS III showed significantly poorer survival rate than those in CS I or II (3-year OS: 12.2% vs. 65.8%, p = 0.0115) and the patients in RPS IV showed significantly poorer survival rate than those in RPS I, II, or III (3-year OS: 11.0% vs. 53.3%, p = 0.000914). Regardless of the therapeutic approaches, patients who achieved hematological CR or cardiac organ response demonstrated significantly improved prognosis. Therefore, achievement of hematological and organ responses is important in the treatment of cardiac AL amyloidosis.

High tibial osteotomy solely for the purpose of return to lifelong sporting activities among elderly patients: A case series study.

Knee osteoarthritis (KOA) is a common joint disease among older individuals, associated with increased mortality rates. The current study was conducted to examine whether open wedge high tibial osteotomy (OWHTO) is an effective treatment for elderly patients with a desire to return to sporting activities (RTS) who do not report inconvenience or pain in activities of daily living. We examined a case series of 9 KOA patients (12 knees) aged 50 or above with a desire for RTS, who underwent HTO. We assessed patients before surgery and 2 years after surgery to evaluate surgical outcomes and RTS. The results revealed that patients' average Japanese Orthopaedic Association score was significantly improved at 2 years after surgery (97.5 ±â€¯4.5), compared with the preoperative score (87.9 ±â€¯7.2; p = 0.008). In addition, the average Tegner activity level score was significantly improved at 2-year follow-up (5.8 ±â€¯1.1) compared with the preoperative score (2.8 ±â€¯1.1; p < 0.001). Eight of nine cases except a marathon runner returned to pre-symptom sporting performance levels. Overall, the current findings suggest that OWHTO provides an appropriate treatment for older KOA patients with a desire for RTS.

[Successful treatment of relapse/refractory multiple myeloma with carfilzomib, lenalidomide, and dexamethasone combination therapy following allogeneic bone marrow transplantation].

A 50-year-old male was diagnosed with multiple myeloma (MM) and treated by high-dose melphalan followed by autologous stem cell transplantation in April 2014. However, he relapsed and received non-myeloablative bone marrow transplantation from an unrelated HLA-matched donor (UR-BMT) in July 2016. After 100 days of UR-BMT, the disease remained stable disease and the patient was treated with carfilzomib, lenalidomide, and dexamethaonse (KRd) therapy. After 10 cycles of KRd, he obtained stringent complete response without exacerbation of graft-versus-host disease. We concluded that KRd after allogeneic stem cell transplantation is one of the useful treatment regimens for relapsed refractory MM.

[Agranulocytosis during therapy of chronic myeloid leukemia lymphoid blast crisis with dasatinib].

A 61-year-old female was diagnosed with a lymphoid crisis of chronic myeloid leukemia (CML) in February 201X and started chemotherapy combined with dasatinib (DAS). After 1 month of initiating second consolidation therapy, the neutrophils decreased to 1%, bone marrow examination revealed large granular lymphocytes (LGL) at 13%, and complete cytogenetic remission was attained (CCyR). Suspecting DAS-induced agranulocytosis, DAS was discontinued. After 2 weeks, LGL disappeared and neutrophils recovered. In this case, CCyR was attained for the first time when LGL increased. We considered that the expansion of LGL correlated with the clinical efficacy, and agranulocytosis was an off-target effect of DAS.

[Possible contribution of disseminated Mycobacterium shigaense infection to development of splenic marginal zone lymphoma].

A 73-year-old male who underwent splenectomy was diagnosed with splenic non-caseating granuloma in May 201X, and sarcoidosis was disregarded from the differential diagnosis. Owing to the persisting inflammation, the patient was carefully followed up with no treatment. Four months post splenectomy, the patient was hospitalized due to progressive dyspnea. Chest computed tomography revealed an encapsulated pleural effusion and lymphocytic infiltration in the left lower lung, with subclavian and mediastinal lymphadenopathy. Although the patient was treated with antibiotics, his condition showed no improvement; therefore, prednisolone 40 mg was administered, resulting in lung lesion improvement. A re-examination of the tissue obtained from the previously removed spleen revealed splenic marginal zone lymphoma (SMZL), a specific low-grade, small B-cell lymphoma. As a result, the patient was treated with rituximab combined with chemotherapy. During the fifth course of the chemotherapy, a subcutaneous abscess appeared in the cervical region, and Mycobacterium shigaense was isolated from the pus discharge, suggesting that the splenic granulomatous lesion formed due to M.shigaense, and dissemination of the Mycobacterium infection occurred following splenectomy and chemotherapy, when the patient was immunosuppressed. Overall, we consider that SMZL developed because of chronic inflammation resulting from a nontuberculous mycobacterial infection.

Pharmacokinetic Interaction Between Tacrolimus and Fentanyl in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND Tacrolimus and fentanyl are well-known cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic range. However, the pharmacokinetic interaction between tacrolimus and fentanyl is unclear. The aim of this study was to determine whether drug interaction exists between tacrolimus and fentanyl. MATERIAL AND METHODS A retrospective study was performed in 6 patients who had received allogeneic hematopoietic stem cell transplantation between April 2010 and March 2015. The patients received continuous intravenous infusion of fentanyl with concomitant use of tacrolimus, and the blood concentrations of tacrolimus were evaluated using fluorescence polarization immunoassay. RESULTS The clearance (CL) of tacrolimus decreased significantly from 1.28 to 0.68 mL/min/kg with concomitant use of fentanyl. The CL changed with time and dose of fentanyl administration. In addition, the CL of tacrolimus was reverted by stopping fentanyl infusion. Horn's drug interaction probability scale indicated a probable category or possible category, suggesting a drug interaction between tacrolimus and fentanyl. No patient showed a difference in hepatic or renal function before and after fentanyl administration. No additional administration of other CYP3A4 inhibitors was observed, suggesting that the drug interaction was mediated by CYP3A4. CONCLUSIONS The influence of fentanyl on the pharmacokinetics of tacrolimus was demonstrated to be of clinical importance. It is proposed that the dose of tacrolimus be reduced by 40% when used in combination with fentanyl.

Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis.

The present study aimed to evaluate the drug interactions between warfarin and combination chemotherapy with lenalidomide and low-dose dexamethasone in immunoglobulin light-chain (AL) amyloidosis patients with unstable international normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis patients treated with warfarin and a combination of lenalidomide and low-dose dexamethasone between March 2011 and February 2015 were analyzed retrospectively. The mean INR value was 1.52 prior to the combination chemotherapy, and the value increased 1.7-fold during treatment. The median time to reach maximum values was 17 days. Horn's drug Interaction Probability Scale indicated a possible interaction between lenalidomide and warfarin. These patients exhibited no marked alterations in hepatic function or serum albumin concentrations prior to and following combination chemotherapy and no additional administration of CYP2C9 inhibitors or vitamin K supplements was conducted. In addition, no patient experienced chemotherapy-induced nausea or appetite loss. These findings suggest that the total clearance or protein binding of warfarin remained unchanged. Therefore, the combination of warfarin and lenalidomide may cause a pharmacodynamic interaction, more likely by inhibiting the production of interleukin-6. In conclusion, clinically important interactions between warfarin and lenalidomide and low-dose dexamethasone therapy were observed in AL amyloidosis patients, where INR values signi ficantly increased. Therefore, close and regular monitoring of patients during the course of treatment is important, and the dose of warfarin should be reduced if required.

CEA-producing multiple myeloma with meningeal invasion during relapse.

Here we describe the case of a 62-year-old woman diagnosed with multiple myeloma (IgA-κ type) who had a high serum CEA level of 27.7 ng/ml. Upper and lower gastrointestinal endoscopy and PET/CT scan showed no abnormality. After two courses of VAD therapy, the serum CEA level decreased to 5.7 ng/ml, with a decrease in the IgA level, suggesting the diagnosis of CEA-producing myeloma. After 4 years and 1 month, she had a relapse with an increase in the LDH level and myeloma cells in the blood, followed by cognitive loss and convulsion. She died 1 month after the onset of neurological symptoms. Several myeloma cells were detected in the cerebral spinal fluid, which suggested the diagnosis of myelomatous meningitis. Myelomatous meningitis is a rare disease and accounts for 1% of all myelomas. This is the fourth reported case of CEA-producing myeloma.

Renal artery stenosis following nilotinib administration in a patient with chronic myelogenous leukemia.

A 63-year-old male was diagnosed as having chronic phase CML in 2001. He obtained a major molecular response with imatinib (IM). In 2012, amulodipin was started for hypertension. In January 2013, IM was switched to nilotinib (NIL) in a clinical trial, and in February 2015, NIL was discontinued because MR4.5 had been maintained for two years. One month later, he was admitted to our hospital because of headache and high blood pressure (194/108 mmHg). His urine test showed protein 3+ and occult blood 2+. His eGFR rapidly deteriorated from 45.6 to 28.5 after admission. MR angiography showed left renal artery stenosis. He thus underwent angioplasty of the left renal artery with a stent implantation. His renal function subsequently improved. Cardiovascular events such as PAOD (peripheral artery occlusive disease) during NIL treatment were recently reported. However, to date, only four cases including our present patient with renal artery stenosis associated with NIL have been reported. These observations suggest assessment of risk factors for cardiovascular events at the start of NIL and careful monitoring to be important during tyrosine kinase inhibitor treatment of CML patients.

[Transition to aggressive phase in a multiple myeloma patient with IgH/CCND1 translocation and diffuse osteosclerotic lesions].

CASE: A 71-year-old woman had been diagnosed as having osteosclerotic myeloma (BJP-λ type) three years prior to the current presentation, based on tumor biopsy from the forehead showing plasmacytoma with systemic osteosclerotic lesions. At 71 years of age, she underwent transverse colectomy for a tumor in the hepatic flexure of the large intestine, and it was diagnosed as IgH/CCND-1-positive plasmacytoma of the large intestine. Although serum vascular endothelial cell growth factor (VEGF) was not elevated, the plasmacytoma was largely positive for VEGF staining. She subsequently experienced transformation to aggressive myeloma over a short period of time. Osteosclerotic myeloma is a rare disease that accounts for less than 3% of all myelomas, and requires differentiation from POEMS syndrome. In this case, peripheral nerve symptoms, which are necessary for the diagnosis of POEMS syndrome, were not confirmed. Thus, this case was diagnosed as having osteosclerotic myeloma. By contrast, abnormal IgH/CCND-1 is confirmed in 15% of patients with myeloma, and 25% of those with POEMS syndrome. While it is unclear whether this genetic abnormality is involved in the development of an osteosclerotic lesion, it is expected that data from patients with osteosclerotic myeloma and POEMS syndrome will be accumulated in the future, allowing clarification of the relationship between the genetic abnormality and osteosclerosis.

The interaction between oral melphalan and gastric antisecretory drugs: Impact on clinical efficacy and toxicity.

The aim of the present study was to clarify whether gastric antisecretory drugs affect the clinical efficacy and toxicity of orally administered melphalan in patients with multiple myeloma. A total of 10 patients receiving bortezomib plus oral melphalan and prednisolone (VMP) therapy between December 2011 and November 2014 were analyzed retrospectively. The patients were divided into a control group (seven patients) and a concomitant group (three patients, who were also administered with gastric antisecretory drugs). The gastric antisecretory drugs included rabeprazole sodium (two patients) and famotidine (one patient). No significant differences between the groups were observed in either the characteristics of the patients or the VMP regimen. The levels of monoclonal protein (M protein) in the control group tended to decrease (with a VMP cycle-dependency), although they were primarily stable in the concomitant group. During the second and third VMP cycles, the levels of M protein were markedly lower in the control group compared with the concomitant group. All the patients in the control group achieved a partial response, whereas those in the concomitant group exhibited stable disease. Hematological toxicity levels were revealed to be comparable between the two groups, whereas gastrointestinal toxicity was more prevalent in the control group. In conclusion, the results of the present study suggested that the clinical efficacy of melphalan may be reduced by the co-administration of gastric antisecretory drugs. This interaction may result in decreased toxicity and clinical efficacy of melphalan.