Terminal Ileac Ulcers Mimicked Post-transplantation Lymphoproliferative Disorder in a Heart Recipient Treated With Everolimus: A Case Report.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL. He was admitted to a local hospital because of fever, abdominal pain, and diarrhea. His symptoms persisted and, 3 weeks later, hematochezia occurred; thus, he was transferred to our hospital. As computed tomography and 18F-fluorodeoxyglucose positron emission tomography showed bowel-wall thickening of the terminal ileum, gastrointestinal PTLD was initially suspected. However, although colonoscopy- performed after switching EVL to mycophenolate mofetil (MMF)-showed terminal ileac ulcers, the histologic examination revealed no findings corresponding to PTLD. As EVL may delay ulcer healing, MMF was maintained for 3 months. After repeated colonoscopy showed ulcer healing, MMF was switched back to EVL for cardiac allograft vasculopathy prevention. Three weeks later, he was emergently admitted to a local hospital for life-threatening gastrointestinal bleeding from a recurrent terminal ileal ulcer, which required hemostatic forceps hemostasis. As EVL is suspected to be associated with recurrent ileal ulcers, EVL was again switched back to MMF. The ileal ulcers resolved, without recurrence in 3 months of clinical follow-up. This case demonstrates that cases of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers can mimic PTLD in a heart recipient treated with EVL.

Clinical Outcomes of Patients With the HeartMate II Left Ventricular Assist Device: A Single-center Experience From Japan.

BACKGROUND: Left ventricular assist device (LVAD) therapy is the "gold standard" alternative therapy for patients with advanced heart failure. However, LVAD therapy is still uncommon in the Asia-Pacific region. Therefore, we aimed to elucidate the clinical outcomes of patients from Japan supported with the HeartMate II (HM-II) LVAD at our institution. METHODS: Ninety-two patients (mean 44.3 ± 12.1 years, 68 men, average body mass index 1.65 ± 0.28 m2; 81 with nonischemic cardiomyopathy) who underwent HM-II implantation for bridge to transplantation (n = 91) or for destination therapy in a clinical study (n = 1) at the National Cerebral and Cardiovascular Center between April 2013 and October 2017 were enrolled in this analysis. Preoperatively, most patients (n = 73, 79%) had an INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile of between level 2 and 4. Postoperatively, the average pump speed was 8602 ± 258 rpm and the hemodynamics were well compensated. RESULTS: Adverse events consisted of 38 (41.3%) hemolysis, 30 (32.6%) major infection, 27 (29.3%) major bleeding (6 [6.5%] with gastrointestinal bleeding), and 18 (19.6%) neurologic dysfunction events. Eighteen patients underwent heart transplantation (HTx) after an average of 32.9 ± 8.9 months of VAD support, and overall survival at both 6 months and 3 years was 96.3%. CONCLUSION: Clinical outcome among patients with HM-II at our institution is satisfactory for both survival and adverse events. The HM-II can provide effective hemodynamic support during the extremely long waiting period for HTx in Japan.

Paradoxical Reaction of Tuberculosis in a Heart Transplant Recipient During Antituberculosis Therapy: A Case Report.

INTRODUCTION: Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. CASE REPORT: We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of miliary TB was made based on the presence of intermittent fever and fatigue; thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide) were started, which led to rapid defervescence and regression of the granular shadow and pleural effusion. However, a new persistent fever and confused state developed 1 month after the anti-TB therapy was started. After excluding possible etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were continued; corticosteroids were added as anti-inflammatory agents. After that, he has shown a favorable course with long-term anti-TB chemotherapy. CONCLUSION: A PR should always be considered when the patients' symptoms of tuberculosis re-exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients with various immunologic conditions including heart transplant recipients.

Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case Report.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a transient cerebrovascular disorder putatively caused by some immunosuppressive agents. CASE REPORT: We recently encountered a 47-year-old female patient diagnosed with dilated cardiomyopathy who developed RCVS after heart transplantation. A triple-drug regimen consisting of tacrolimus, mycophenolate mofetil, and a corticosteroid was started after surgery. On postoperative day (POD) 11, the patient developed a severe headache, although computed tomography of the head demonstrated no signs of hemorrhage or infarction. At first, both a painkiller and migraine drugs were regularly administered to the patient. On POD 21, however, she developed an unbearable headache with a visual field defect and mild hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain revealed a cerebral infarction in the left occipital lobe with diffuse vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was discontinued. In its place, two doses of basiliximab followed by everolimus, both of which are alternatives for tacrolimus, were given. The corticosteroid dose was also increased. Furthermore, to release vasoconstriction, both verapamil and diltiazem were administered. On POD 27, cerebrovascular constrictions were shown to be relieved on brain MRI and the patient's neurological symptoms subsequently almost completely diminished. CONCLUSION: RCVS should always be considered as a cause of headache in heart transplant recipients because tacrolimus, an immunosuppressive agent, may trigger RCVS. This will allow rapid intervention that is essential for avoiding irreversible neurological deficits.

Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting in Heart Transplant Recipients With Transplant Coronary Arterial Vasculopathy.

BACKGROUND: Transplant coronary arterial vasculopathy (TCAV) is a major cause of death after heart transplantation (HTx). Palliative coronary revascularization has been attempted in patients with severe TCAV; however, the outcome has not been fully elucidated. METHODS: Ninety-six patients who were treated after HTx at our institute between 1999 and 2015 were screened for TCAV. TCAV was defined as >70% stenosis on coronary angiography (CAG) or a maximal intimal thickness of >0.5 mm in the right or left coronary arteries on intracoronary ultrasonography (IVUS). In the present study, the outcomes of patients with severe TCAV who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were investigated. RESULTS: TCAV containing donor-transmitted atherosclerosis was cumulatively found in 69 patients (71.9% of the total; mean age, 34.6 ± 13.1 years; 52 men; mean follow-up duration, 83.0 ± 60.4 months). Five (7.2%) and 64 (92.8%) of the 69 patients were diagnosed as having TCAV by use of CAG and IVUS, respectively. All 5 patients diagnosed by with the use of CAG underwent coronary revascularization between 1 and 236 months after HTx. Three patients underwent PCI with drug-eluting stents, with a primary success rate of 100%. No angiographic restenosis occurred in 2 patients at 31 and 36 months after PCI, respectively. Meanwhile, 2 patients underwent CABG. No peri-operative complications occurred, and all grafts were patent as assessed by use of CAG at 34 and 5 months after CABG. CONCLUSIONS: Coronary revascularization was feasible and effective for severe TCAV with middle-term follow-up.

Diffuse Liver Metastasis of Small-Cell Lung Cancer Presenting as Acute Liver Failure and Diagnosed by Transjugular Liver Biopsy: A Rare Case in Whom Nodular Lesions Were Detected by Enhanced CT Examination.

Small-cell lung cancer (SCLC) is a subgroup of lung cancer with a high frequency of liver metastasis, which is a predictor of poor prognosis. Diffuse liver metastases of SCLC with no visible nodular lesions in the liver when examined using computed tomography (CT) are relatively rare; however, a few cases with rapid progression to acute liver failure that were diagnosed after death have been reported. In this paper, we report a 63-year-old man with diffuse liver metastases of SCLC that were histologically diagnosed using a transjugular liver biopsy while the patient was alive, even though no lesions were visible during a contrast-enhanced CT examination.

Natural history of bleeding risk in colonic diverticulosis patients: a long-term colonoscopy-based cohort study.

BACKGROUND: The natural history of bleeding risk from colonic diverticulosis remains unclear. AIM: To identify the incidence of bleeding in colonic diverticulosis patients and associated risk factors. METHODS: A cohort of 1514 patients with colonoscopy-confirmed asymptomatic diverticulosis was selected between 2001 and 2013. Age, sex and location of colonic diverticulosis (right or left side, or bilateral) were assessed. The endpoint was a bleeding event, and data were censored at the time of last colonoscopy. The cumulative and overall incidences of bleeding were estimated using the Kaplan-Meier and person-years methods. The Cox proportional hazards model was used to estimate age- and sex-adjusted hazard ratios (aHRs). RESULTS: The median follow-up period was 46 months. Bleeding events occurred in 35 patients, and the median time-to-event interval was 50 months. Kaplan-Meier analysis showed that the cumulative incidence of diverticular bleeding was 0.21% at 12 months, 2.2% at 60 months and 9.5% at 120 months. By the person-years method, the overall incidence rate of bleeding was 0.46 per 1000 patient-years. On multivariate analysis, age ≥70 (aHR. 3.7) and bilateral diverticulosis (aHR, 2.4) were significant risk factors for bleeding. CONCLUSIONS: This long-term follow-up study demonstrated that the cumulative incidence of bleeding from diverticulosis was approximately 2% at 5 years and 10% at 10 years, and the overall incidence was 0.46 per 1000 patient-years. Bilateral diverticulosis increased the risk of bleeding.

Tissue characterization of progressive cardiac allograft vasculopathy in patients with everolimus therapy compared with donor-transmitted atherosclerosis assessed using serial intravascular imaging: a case report.

Using serial intravascular ultrasound (IVUS), integrated-backscatter IVUS, and optical coherence tomography, we observed rapidly progressive cardiac allograft vasculopathy (CAV) and donor-transmitted plaque in the left anterior descending artery. Late-phase everolimus-resistant CAV had a rapidly progressive course (maximal intimal thickness [MIT] increased by 0.5 mm between years 3 and 4 after cardiac transplantation, from MIT growth<0.5 mm at year 1). Conversely, the donor-transmitted plaque grew slowly (0.1 mm increase during the same period). Tissue characteristics in the 2 segments were also different; CAV had eccentric, noncalcified, and lipid-rich components and was associated with macrophage accumulation, whereas donor-transmitted atherosclerosis presented with typical features of atherosclerosis (ie, fibrocalcific plaque). CAV with late-phase progression involves everolimus resistance and features of vulnerable plaques seen in nontransplantation patients and is independent of donor-transmitted atherosclerosis.

Importance of early appropriate intervention including antibiotics and wound care for device-related infection in patients with left ventricular assist device.

INTRODUCTION: A left ventricular assist device (LVAD) is essential for treating patients with advanced heart failure. However, LVAD-related infection is a significant cause of mortality and morbidity, with bloodstream infection (BSI) especially associated with high mortality. We investigated the incidence of infectious complications in patients who received an LVAD and evaluated the effects of early and appropriate intervention for LVAD-related infection. METHOD: We retrospectively reviewed 27 consecutive patients who underwent continuous-flow LVAD (CF-LVAD; n = 16) or pulsatile-flow LVAD (PF-LVAD; n = 11) implantation at the National Cerebral and Cardiovascular Center between April 2011 and March 2013. Incidences of LVAD-related infections, such as drive-line infection in patients with CF-LVAD, cannula infection in patients with PF-LVAD, and BSI in patients with both types, were examined (follow-up period, 342 ± 229 days). The mandatory antibiotic prophylaxis protocol at our institution includes teicoplanin (400 mg) 2 days before LVAD implantation and doripenem (1000 mg) within 1 hour of skin incision. In addition, the driveline exit sites undergo sterile cleansing with diluted hydrogen peroxide and placement of an antimicrobial occlusive dressing for wound care, with dressing changes performed 2-3 times per day. RESULTS: More than 90% of all patients suffered from a drive-line infection within 12 months after LVAD implantation. However, BSI developed in only 12.5% of CF-LVAD and 10% of PF-LVAD patients within 12 months (log-rank test; P = .875). CONCLUSIONS: LVAD-related infections, such as drive-line and cannula infections, were common, whereas the incidence of BSI was low in our LVAD-implanted patients. Our results highlight the importance of early and appropriate intervention including antibiotics and wound care for device-related infections for reducing the incidence of potentially fatal BSI.

The pharmacokinetics and pharmacodynamics of tolvaptan in patients with liver cirrhosis with insufficient response to conventional diuretics: a multicentre, double-blind, parallel-group, phase III study.

OBJECTIVES: This study investigated the pharmacokinetic and pharmacodynamic profile of tolvaptan, and verified its efficacy and safety in patients with liver cirrhosis-associated ascites, with insufficient response to conventional diuretic treatment. METHODS: This multicentre, double-blind, parallel-group study allocated patients with cirrhosis to receive either 3.75 or 7.5 mg/day tolvaptan orally, once daily, for 7 days. Pharmacokinetic, pharmacodynamic and efficacy variables were measured. RESULTS: Tolvaptan was shown to have high plasma concentrations, and prolonged duration of maximum concentration and half life, in these patients with impaired hepatic function. Tolvaptan resulted in dose-dependent decreases in body weight and ascites volume, and increases in urine output. There were no effects on urinary or serum electrolytes. Tolvaptan was well tolerated, with a good safety profile. CONCLUSIONS: Tolvaptan at 3.75 mg/day exerts some effects due to the pharmacokinetic profile in patients with liver cirrhosis. Tolvaptan at 7.5 mg/day is a clinically useful option for treating patients who do not respond well to conventional diuretics.

The persistence of drug-induced fever by teicoplanin--a case report.

OBJECTIVE: It was reported that the drug-induced fever of teicoplanin tended to persist after cessation of treatment. It is considered that the long half-life of teicoplanin causes the phenomenon. However there was no detailed report regarding plasma concentration of teicoplanin during onset of drug induced-fever. Therefore we investigated the relation between persistence of drug-induced fever and plasma concentration of teicoplanin. CASE: A 38-year-old male patient on the Left Ventricular Assist System (LVAS) was treated with teicoplanin for methicillin-resistant Staphylococcus aureus (MRSA) and he experienced drug-induced fever. Plasma concentrations of teicoplanin were measured not only during the treatment with the drug but also after it was discontinued. As such, plasma concentration was measured even when the fever had subsided. RESULTS: On Day 9 of treatment, the dose was increased from 400 to 600 mg, but the patient had a fever of about 38 - 39 °C. When the treatment was discontinued, it took 9 days for the fever to subside to a temperature of about 37 °C. The half-life of elimination of teicoplanin in the elimination phase is about 108 h, which is long. The fever persisted until the plasma concentration decreased to below 10 µg/ml, which is the effective trough concentration, and subsided when the estimated blood concentration was 7.5 µg/ml. CONCLUSIONS: We suggest that there is the possibility that the drug-induced fever due to teicoplanin persisted until the plasma concentration had decreased adequately. Close monitoring of plasma concentration is necessary, particularly when teicoplanin clearance is decreased such as in patients with renal dysfunction.

Influence of IOP measurement through the wrong eyepiece of the slit lamp on Goldmann applanation tonometry.

PURPOSE: This study examined whether intraocular pressure (IOP) measurements through the wrong eyepiece of the slit lamp may be a source of error. METHODS: Seven skilled observers measured the IOP from seven healthy subjects. The observers used a Haag-Streit Goldmann applanation tonometer with two types of slit lamps (Haag-Streit and Rodenstock). In the Haag-Streit slit lamp the prism of the tonometer is aligned with the right part of the slit lamp optics. Conversely, in the Rodenstock slit lamp, the prism is aligned with the left. Each observer measured the IOP of each subject through the right eyepiece, through the left eyepiece, and under binocular vision. RESULTS: The IOP measured with the left eyepiece of the Haag-Streit slit lamp was significantly higher than that measured with the right eyepiece and binocular vision. The IOP measured with the right eyepiece of the Rodenstock slit lamp was significantly higher than that measured with the left eyepiece and binocular vision. CONCLUSIONS: IOP measurement through the wrong eyepiece of the slit lamp may be a source of error.

Three-dimensional images for surgical plan of giant sacral schwannoma.

OBJECTIVE: Documentation of three-dimensional (3D) images of a giant sacral schwannoma with intrapelvic expansion. SETTING: Nagoya University, Nagoya, Japan. RESULTS: 3D computed tomography (3D CT) showed a destructed bony region clearly. 3D CT angiography clarified the positional relationship between tumor and iliac arteries. Resection procedure was safely completed based on these 3D evaluations. CONCLUSION: 3D images were helpful to make a surgical plan and to complete this complicated resection combined with sacroiliac reconstruction.

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma.

Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma.

Risk factors for multiple intravesical recurrences of superficial bladder cancer.

OBJECTIVES: To elucidate the risk factors for a second or third intravesical recurrence in patients with superficial bladder cancer. METHODS: Of 84 consecutive patients newly diagnosed as having superficial bladder cancer in Sapporo Medical University Hospital, 30 patients who had at least one recurrent superficial bladder cancer and were followed up for more than 3 years were included in this study. Multivariate analysis by Cox's proportional hazards model was used to determine which clinical and pathologic variables significantly affected the second and third recurrences. Stepwise regression analysis was used to determine which clinical and pathologic variables significantly affected multiple recurrences of bladder cancer. RESULTS: The 1, 2, and 5-year recurrence-free rates as determined by the Kaplan-Meier method were 66.1%, 43.8%, and 29.8% for a second recurrence and 67.4%, 61.8%, and 39.2% for a third recurrence, respectively. Multivariate analysis revealed that only the interval between the initial transurethral resection of the bladder cancer and the first recurrence was a significant and independent factor affecting the second recurrence. In the study of the third recurrence, the interval between the first and second recurrences was the only definite risk factor for the third one. When multiple recurrences were considered, stepwise regression analysis revealed that a time of 6 months or less from the initial transurethral resection until the first recurrence was a significant factor that affected the total frequency of bladder cancer recurrence (R(2) = 0.220, P = 0.0078). CONCLUSIONS: The results of our study indicate that patients will have the potential for frequent recurrences if they have the disease with recurrence after a short interval. This result may contribute to the selection of patients with superficial bladder cancer to receive aggressive adjuvant treatments to prevent frequent recurrences.

Growth rates of primary and metastatic lesions of renal cell carcinoma.

BACKGROUND: The natural history and growth rate of renal cell carcinoma (RCC) have not yet been determined. The growth rates of primary lesions in incidentally found RCC were compared with those of metastatic lesions. METHODS: Sixteen patients who did not receive immediate surgical treatment for renal solid masses that were later proven to be RCC were reviewed retrospectively. All primary lesions of the 16 patients were found incidentally. For comparison, metastatic lesions were evaluated in another 16 patients with RCC. Of these, 11 underwent surgical treatment for the primary lesions. RESULTS: The growth rates of primary and metastatic lesions of RCC varied. They ranged from 0.10 to 1.35 cm/year for primary lesions and from 0.08 to 7.87 cm/year for metastatic lesions. The growth rate of primary lesions of incidentally found RCC was lower than that of metastatic lesions (P = 0.0159). The initial tumor diameter and pathological grade did not affect the growth rate of the primary lesion of incidentally found RCC. However, a close correlation was found between the growth rate of metastatic lesions and the pathological grade of the primary lesion in patients with metastasis. CONCLUSIONS: The growth rate of incidentally found RCC varied. Some patients with the disease may be candidates for 'watchful waiting' when an immediate surgical treatment is not indicated, but they should be selected with great caution.

[Destructed knee in patient with systemic lupus erythematosus treated with total knee arthroplasty: a case report].

We reported a case of a 61-year-old female with arthritis of right knee associated with systemic lupus erythematosus (SLE). She suffered from SLE at age 31 and felt pain around her right knee at age 60. It gradually increased despite intraarticular injections of steroid and arthroscopic synovectomy. On admission, the range of motion of her right knee was 20 to 135 degrees and remarkable gait disturbance were noted due to the pain. Radiographs of the right knee showed joint space narrowing and bone erosion. YMCK total knee arthroplasty was performed. Operation findings showed smooth and thick synovium and cartilage defect. Histological examination revealed fibrin on surface, proliferad connective tissue and newly development of vasculature. Synovium eroded both cartilage and bone. In SLE, soft tissue contructure was reported to be a main cause of joint dislocation, but there were only a few report of progressive joint destruction due to SLE. In this case, the main cause of joint destruction may be invasion synovium into cartilage and bone.

External venous shunt as a solution to venous thrombosis in microvascular surgery.

We report a case in which venous occlusion occurred after fibular osteocutaneous flap transfer for open tibial fracture. The flap was salvaged using an external venous shunt. The shunt consisted of a Teflon catheter for intravenous infusion, a three-way stopcock, a urokinase-immobilised catheter and a pressurising bag for arterial-pressure monitoring. This method can be used to establish venous drainage when there is no accessible recipient vein. It may improve the success rate of microvascular surgery and extend the indications for surgery.

The mitogenic activity of hepatocyte growth factor on rat hepatocytes is dependent upon endogenous transforming growth factor-alpha.

Both transforming growth factor-alpha (TGF-alpha) and hepatocyte growth factor (HGF) induce DNA synthesis in hepatocytes in vitro and in vivo. Hepatic and circulating levels of HGF have been reported to increase before an increase in TGF-alpha levels in several rat models of liver regeneration. In addition, serum TGF-alpha levels increase after an increase in serum HGF levels in patients with either partial hepatectomy or acute hepatitis. In this study, we investigate the significance of TGF-alpha in hepatocyte proliferation. TGF-alpha contents and DNA synthesis in cultured rat hepatocytes increased in response to HGF addition to the culture medium in a dose-related manner. These increases were suppressed by the addition of anti-sense TGF-alpha mRNA oligonucleotide. Furthermore, the addition of anti-TGF-alpha rabbit IgG suppressed the increase in DNA synthesis. When the anti-TGF-alpha antibody was administered to rats after partial hepatectomy, the number of mitotic hepatocytes was reduced in comparison to rats treated with normal rabbit IgG. These results were observed even though hepatic HGF levels were increased equally in rats given either anti-TGF-alpha antibody or normal rabbit IgG. Our results suggest that HGF stimulates TGF-alpha production in rat hepatocytes, and that the mitogenic activity of HGF depends on endogenous TGF-alpha activity.