Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study.

Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication. INTRODUCTION: This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent. METHODS: Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not. CONCLUSIONS: These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.

Medication-related osteonecrosis of the jaw after tooth extraction in cancer patients: a multicenter retrospective study.

Root amputation, immunosuppressive therapy, mandibular tooth extraction, pre-existing inflammation, and longer duration of treatment with bone-modifying agents were significantly associated with an increased risk of medication-related osteonecrosis of the jaw. Hopeless teeth should be extracted without drug holiday before the development of inflammation in cancer patients receiving high-dose bone-modifying agents. INTRODUCTION: No studies have comprehensively analyzed the influence of pre-existing inflammation, surgical procedure-related factors such as primary wound closure, demographic factors, and drug holiday on the incidence of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this study was to retrospectively investigate the relationships between these various factors and the development of MRONJ after tooth extraction in cancer patients receiving high-dose bone-modifying agents (BMAs) such as bisphosphonates or denosumab. METHODS: Risk factors for MRONJ after tooth extraction were evaluated with univariate and multivariate analyses. The following parameters were investigated in all patients: demographics, type and duration of BMA use, whether BMA use was discontinued before tooth extraction (drug holiday), the duration of such discontinuation, the presence of pre-existing inflammation, and whether additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. RESULTS: We found that root amputation (OR = 22.62), immunosuppressive therapy (OR = 16.61), extraction of mandibular teeth (OR = 12.14), extraction of teeth with pre-existing inflammation, and longer duration (≥ 8 months) of high-dose BMA (OR = 7.85) were all significantly associated with MRONJ. CONCLUSIONS: Tooth extraction should not necessarily be postponed in cancer patients receiving high-dose BMA. The effectiveness of a short-term drug holiday was not confirmed, as drug holidays had no significant impact on MRONJ incidence. Tooth extraction may be acceptable during high-dose BMA therapy until 8 months after initiation.

Upsizing the femoral component increases patellofemoral contact force in total knee replacement.

In posterior stabilised total knee replacement (TKR) a larger femoral component is sometimes selected to manage the increased flexion gap caused by resection of the posterior cruciate ligament. However, concerns remain regarding the adverse effect of the increased anteroposterior dimensions of the femoral component on the patellofemoral (PF) joint. Meanwhile, the gender-specific femoral component has a narrower and thinner anterior flange and is expected to reduce the PF contact force. PF contact forces were measured at 90°, 120°, 130° and 140° of flexion using the NexGen Legacy Posterior Stabilized (LPS)-Flex Fixed Bearing Knee system using Standard, Upsized and Gender femoral components during TKR. Increasing the size of the femoral component significantly increased mean PF forces at 120°, 130° and 140° of flexion (p = 0.005, p < 0.001 and p < 0.001, respectively). No difference was found in contact force between the Gender and the Standard components. Among the patients who had overhang of the Standard component, mean contact forces with the Gender component were slightly lower than those of the Standard component, but no statistical difference was found at 90°, 120°, 130° or 140° of flexion (p = 0.689, 0.615, 0.253 and 0.248, respectively). Upsized femoral components would increase PF forces in deep knee flexion. Gender-specific implants would not reduce PF forces.

Enlarged post-operative posterior condyle tightens extension gap in total knee arthroplasty.

We investigated whether the extension gap in total knee replacement (TKR) would be changed when the femoral component was inserted. The extension gap was measured with and without the femoral component in place in 80 patients with varus osteoarthritis undergoing posterior-stabilised TKR. The effect of a post-operative increase in the size of the femoral posterior condyles was also evaluated. The results showed that placement of the femoral component significantly reduced the medial and lateral extension gaps by means of 1.0 mm and 0.9 mm, respectively (p < 0.0001). The extension gap was reduced when a larger femoral component was selected relative to the thickness of the resected posterior condyle. When the post-operative posterior lateral condyle was larger than that pre-operatively, 17 of 41 knees (41%) showed a decrease in the extension gap of > 2.0 mm. When a specially made femoral trial component with a posterior condyle enlarged by 4 mm was tested, the medial and lateral extension gaps decreased further by means of 2.1 mm and 2.8 mm, respectively. If the thickness of the posterior condyle is expected to be larger than that pre-operatively, it should be recognised that the extension gap is likely to be altered. This should be taken into consideration when preparing the extension gap.

[Large saphenous vein graft aneurysm after coronary artery bypass grafting].

A 64-year-old man underwent coronary artery bypass grafting (CABG) in 1994. Eleven years later, coronary angiography (CAG) showed a saphenous vein graft (SVG) aneurysm. In April 2008, the CAG demonstrated enlargement of the aneurysm. Enhanced computed tomography showed a large aneurysm measuring 53 x 44 mm in diameter of the SVG-right coronary artery (RCA) [#3] anastomosis. Off-pump coronary surgery to RCA and aneurysmectomy was planned through a median epigastric incision. However re-grafting was difficult because of severe adhesion and calcification of the coronary artery. We confirmed sufficient back flow from the distal coronary artery without hemodynamic and electrocardiographic changes under SVG clamp. Aneurysmectomy was then performed without coronary bypass. The patient was discharged 9 days after surgery and has been well for 8 months in outpatient clinic.

Laboratory and febrile features after joint surgery in patients with rheumatoid arthritis treated with tocilizumab.

OBJECTIVES: To understand the acute phase responses to surgical intervention in patients with rheumatoid arthritis (RA) treated with the anti-interleukin (IL)6 receptor antibody, tocilizumab. METHODS: In a retrospective 1:1 pair-matched case-control study, 22 tocilizumab-treated RA cases and 22 cases treated with conventional disease-modifying antirheumatic drugs (DMARDs) and matched for type of surgery, age and sex were evaluated for body temperature every day, and blood C-reactive protein (CRP) levels and white blood cell (WBC), neutrophil and lymphocyte counts on days -1, 1, 3 and weeks 1 and 2 after joint surgery. Safety issues were also monitored. RESULTS: No complications of infection or delay of wound healing occurred in either patient group. Tocilizumab partially, but significantly, suppressed the increase in body temperature on postoperative days 1 and 2, compared with DMARDs (average (SD) maximum increase in temperature was 0.45 (0.1) degrees C in the tocilizumab group and 0.78 (0.1) degrees C in the DMARD group; p<0.01). Tocilizumab completely suppressed the increase in CRP after surgery, whereas all cases treated with DMARDs showed a significant increase of CRP at postoperative day 1 (5.5 (0.6) mg/dl; p<0.001). WBC, neutrophil and lymphocyte counts showed no remarkable change after surgery, and there was no significant difference in any cell counts between the patient groups. CONCLUSIONS: Within this small number of cases, safe operations on patients were performed during tocilizumab treatment. Tocilizumab suppressed fever and increase of CRP after surgery, whereas there was no influence on the transition in number of leukocytes. This characteristic postoperative response should be considered during tocilizumab treatment.

[Proximal anastomotic pseudoaneurysm due to gelatin-resorcin-formalin (GRF) glue after replacement of ascending aorta for acute aortic dissection; report of a case].

A 78-year-old man had previously undergone replacement of ascending aorta using gelatin-resorcin-formalin (GRF) glue for acute aortic dissection. Five years later, a follow-up computed tomography (CT) showed an aortic root pseudoaneurysm. Ultrasound cardiography revealed moderate aortic regurgitation and pseudoaneurysm of aortic root. Aortic root replacement was planned based on a clinical diagnosis of an anastomotic pseudoaneurysm of the aortic root. The patient was discharged without complication 26 days after surgery. In the histopathological examination, the necrotic change of smooth muscle cells in the aortic media was revealed. Previous reports suggests that the use of GRF glue for reconstructing the dissected aorta results in higher rates of postoperative redissection or pseudoaneurysm. Therefore, careful postoperative follow-up is necessary in such cases and further improvements in the quality of glue or alternative methods will be necessary to prevent problems in the first place.

Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension.

BACKGROUND: Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems. OBJECTIVES: We hypothesized that PCI participates in the pathogenesis of pulmonary hypertension. To demonstrate this, we compared the development of pulmonary hypertension in mice overexpressing PCI in the lung with wild-type (WT) mice. Pulmonary hypertension was induced by s.c. injection of 600 mg kg-1 of monocrotaline weekly for 8 weeks. RESULTS: Right ventricular arterial pressure was significantly increased in monocrotaline-treated WT mice compared with that in monocrotaline-treated transgenic mice. Bronchoalveolar lavage fluid (BALF) levels of thrombin-antithrombin complex, monocyte chemoattractant protein-1 and platelet-derived growth factor, and the plasma level of tumor necrosis factor-alpha were significantly increased in monocrotaline-treated WT mice as compared with monocrotaline-treated PCI transgenic mice. Increased level of PCI-thrombin complex was detected in BALF from monocrotaline-treated PCI transgenic mice as compared with saline-treated PCI transgenic mice. CONCLUSIONS: This study showed that increased expression of PCI in the lung is protective against monocrotaline-induced pulmonary hypertension, suggesting a potential beneficial effect of PCI for the therapy of this disease.

Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration.

Transcriptional dysregulation as a result of sequestration of essential transcription factors into protein aggregates formed by polyglutamine (polyQ) expansions can lead to late-onset progressive neurodegeneration. DNA microarray analysis of Drosophila expressing polyQ in the compound eye over time revealed large numbers of transcriptional changes at the earliest stages of the disease including repression of the transient receptor potential calcium channels in a polyQ-induced cell death specific manner. While significant differences in expression profiles were found between the Drosophila compound eye and polyQ-sensitive neural cells, a number of possible key overlapping regulators were extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity, suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.

Resection of hepatocellular carcinoma in a patient with congenital anomaly of the portal system.

Hepatic resection in a patient with an anomalous portal vein system is presented. A 53-year-old man was referred to our hospital for hepatic resection. Preoperative computed tomography (CT) and angiography demonstrated that the umbilical portion of the portal vein gave off major branches to the right anterior segment, and the hepatic tumor was located on the dorsal side of one of the right anterior portal branches near the umbilical portion. Partial hepatic resection was performed using the indocyanine green staining technique under operative echo guidance. Limited hepatic resection was indicated due to the patient's poor hepatic reserve function. His postoperative course was uneventful. This case emphasizes the importance of delineating the hepatic vascular anatomy before and during operation, especially in the case of an anomalous portal vein system.

[Traumatic aortic regurgitation with an ascending aortic aneurysm: report of a case].

We reported a case of an aortic regurgitation due to nonpenetrating chest trauma with an ascending aortic aneurysm. A 58-year-old man was admitted to our hospital with an acute left cardiac failure. Severe aortic regurgitation and ascending aortic aneurysm were diagnosed on ultrasonic echocardiography (UCG) and computed tomography (CT) scan. On the 13th day after the injury, semi-emergency operation was done. The commissure between the right coronary and non-coronary cups was torn, and modified Bentall operation was performed. The patient recovered well and discharged uneventfully.

Autologous blood storage before hepatectomy for hepatocellular carcinoma with underlying liver disease.

BACKGROUND: Preoperative autologous blood donation has been suggested for patients with liver disease who are to undergo liver resection. The aim of this retrospective study was to clarify the risk factors for increased blood loss and the need for blood transfusion during hepatectomy for hepatocellular carcinoma (HCC). METHODS: From January 1996 to December 2000, 206 consecutive patients, 98.5 per cent of whom had underlying liver disease, underwent elective hepatectomy for HCC. RESULTS: Major hepatectomy was performed in 34 patients (16.5 per cent) and minor hepatectomy in 172 patients (83.5 per cent). The mean blood loss was 410 (median 260) ml. Eleven (5.3 per cent) of the 206 patients received blood transfusion during or after the operation. Operation time (P = 0.004) and central venous pressure (CVP) (P = 0.041) were independently correlated with blood loss of more than 1000 ml. Only preoperative haemoglobin level (P = 0.001) was independently correlated with the need for blood transfusion. CONCLUSION: In patients with underlying liver disease, maintaining CVP at a level below 5 cm H2O during parenchymal transection to reduce blood loss is more important than reserving autologous blood before the operation.

[Angina pectoris with a left atrial myxoma; report of a case].

A 78-year-old woman who had been diagnosed as left atrial myxoma and angina pectoris underwent simultaneous coronary artery bypass grafting (CABG) and resection of the left atrial myxoma. CABG was preceded by resection of myxoma to avoid systemic embolism of fragment of myxoma. Myocardial protection was secured by combination of antegrade and retrograde infusion of cardioplegia. The patient recovered well and discharged uneventfully.

[A case of mitral regurgitation with a giant thrombus thought to be caused by anti-phospholipid syndrome].

A 58-year-old woman suffered from mitral valve regurgitation with a giant thrombus in right atrium was thought to be complicated by anti-phospholipid syndrome (APS). Positive anti-loops anti-coagulant and histories of cerebral infarction and miscarriage strongly indicated the diagnosis of APS. She underwent mitral valve replacement using bileaflet mechanical prosthetic value and removal of thrombus. She recovered uneventfully and strict anti-coagulation therapy has been continuing.

Hearing changes and questionnaire responses in patients with paramedian suboccipital vestibular neurectomy.

In order to determine the effectiveness of paramedian suboccipital transmeatal vestibular neurectomy, pre- and postoperative neurotological studies were conducted and questionnaire responses of 30 patients who underwent surgery were evaluated. Hearing was maintained within 10 dB of the preoperative level or improved in 54% of patients 2 years after surgery. Questionnaire responses indicated that all patients suffering from intractable vertigo experienced no vertiginous symptoms after surgery. Based on this study, we conclude that paramedian suboccipital transmeatal vestibular neurectomy is a useful method for relieving ear-related vertigo.

Percutaneous microwave coagulation therapy for primary or recurrent hepatocellular carcinoma: long-term results.

BACKGROUND/AIMS: To clarify the indication of percutaneous microwave coagulation therapy for hepatocellular carcinoma. METHODOLOGY: Thirty-three hepatocellular carcinoma patients who underwent percutaneous microwave coagulation therapy were enrolled in this study, including 18 primary and 15 recurrent hepatocellular carcinoma patients. We examined the local recurrence rates and the long-term results after the treatment. RESULTS: The overall survival rates of the primary group at 1, 2, 3, 4 and 5 years were 94.4%, 77.8%, 77.8%, 77.8% and 48.6%, respectively, whereas those of the recurrent group were 100%, 85.7%, 66.7% and 50.0% at 1, 2, 3 and 4 years, respectively. Local recurrence after percutaneous microwave coagulation therapy was found in about 50% of patients in both groups. Seventeen of the 27 patients (63.0%) with a moderately or poorly differentiated hepatocellular carcinoma tumor had local recurrence, while none of the 6 patients with a well-differentiated hepatocellular carcinoma tumor did (P = 0.005). CONCLUSIONS: Irrespective of primary or recurrent hepatocellular carcinoma, the indication of percutaneous microwave coagulation therapy as an alternative to hepatic resection should be limited to cases of a well-differentiated hepatocellular carcinoma tumor smaller than 2 cm in diameter.

Hepatic resection for intrahepatic cholangiocarcinoma: relation to gross tumor morphology.

BACKGROUND/AIMS: The aim of this study was to investigate the clinicopathologic features and biological behaviors related to the gross appearance of intrahepatic cholangiocarcinoma. METHODOLOGY: Fourteen patients with intrahepatic cholangiocarcinoma who underwent hepatic resection between 1986 and 1998 were divided into four groups according to the gross appearance of the tumor: ID (intraductal growth) type (n = 1), PD (periductal-infiltrating) type (n = 4), MF (mass-forming) type (n = 5), MF-with-PD type (n = 4). RESULTS: Overall survival at 1, 5, and 10 years was 50.0%, 35.7%, and 35.7%, respectively. All three long-term survivors without recurrence had tumors unassociated with vascular invasion, intrahepatic metastasis, or lymph node metastasis. The MF and MF-with-PD tumors were more frequently associated with vascular invasion and/or lymph node metastasis than the ID or PD type. The Ki-67-positive grade of the cancer cells was clearly higher in the MF and MF-with-PD tumors than in the ID or PD type. All of the cases of MF-with-PD tumors were stage IV-A and had a poor outcome. CONCLUSIONS: Extended hepatic resection with a sufficient surgical margin yielded good results in intrahepatic cholangiocarcinoma patients without vascular invasion, intrahepatic metastasis, or lymph node metastasis. However, it is necessary to develop a new effective strategy for advanced intrahepatic cholangiocarcinomas, such as the MF-with-PD type.

Three-dimensional MR imaging of mammographically detected suspicious microcalcifications.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value and clinical significance of three-dimensional MR imaging of the breast in patients with mammographically detected suspicious microcalcifications. METHODS: Forty patients with suspicious microcalcifications on mammography were evaluated with three-dimensional MR imaging. MR findings were grouped mainly by distribution of abnormal enhancement (linear, focal-clumped, segmental-clumped, segmental-stippled and diffuse-stippled). These findings were compared with the mammography findings according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS) and histopathologic data. RESULTS: Twenty patients had proven malignancies, most frequently ductal carcinoma in situ. For all the cases, linear (100%) and segmental-clumped type (100%) enhancement on MR imaging showed a significantly higher risk for malignancy. Diffuse stippled type (7%) and no enhancement (0%) on MR imaging indicated the lowest possibility of malignancy. 3D-MR imaging showed a sensitivity of 90%, a specificity of 95% and an overall accuracy of 93% in this study. CONCLUSIONS: Three-dimensional MR imaging of the breast can more accurately diagnose ductal carcinoma in situ. Combined with mammography, this procedure is useful for reducing the number of false-positive biopsies and helpful for deciding the better management of patients with mammographically detected suspicious microcalcifications.

[Two cases of left main trunk lesion treated with coronary artery bypass grafting the proximal circumflex coronary artery (# 11)].

Two cases are reported of coronary artery bypass graft (CABG) surgery to the proximal left circumflex artery (LCX) system and left anterior descending artery (LAD) system. Both patients suffered from unstable angina due to left main trunk (LMT) lesions and required semi-emergent coronary revascularization. In both cases, the obtuse marginal branch and postero-lateral branch were too small to be grafted, although there are the usual target branches in the LCX system. CABG to the proximal portion (# 11) of LCX in the atrioventricular groove using saphenous vein grafts was performed and good blood flow rates were seen intra-operatively. Both patients recovered uneventfully and had no recurrence of anginal attacks. Postoperative coronary angiography confirmed good graft patency and an adequate coronary blood supply. CABG to LCX (# 11) is feasible without special techniques or tools. This method seems to be useful in patients with LMT lesions or with proximal lesions of LCX in which the branches are too small to be grafted.