A novel method to bail out coronary perforation: Micro-catheter distal perfusion technique.

Coronary perforation is a rare, but life-threatening complication during percutaneous coronary intervention. Prolonged balloon inflation is one option for achieving hemostasis, but it often causes ST elevation, chest pain, decreased blood pressure, or fatal arrhythmia due to ischemia. We present the case of a 73-year-old woman who suffered severe coronary perforation after stent implantation and post-dilatation. To allow prolonged balloon inflation without ischemia, we perfused the distal area with the patient's own arterial blood injected via micro-catheter. With this method, we could prolong balloon inflation for 20 min, successfully achieving hemostasis. This novel technique, which we named the "distal perfusion technique," is useful to minimize ischemia during prolonged balloon inflation.

Cusp-Level Chordal Shortening for Non-Rheumatic Mitral Anterior Leaflet Prolapse in a Patient with Persistent Atrial Fibrillation.

The case is reported of mitral valve repair with cusp-level chordal shortening for non-rheumatic mitral anterior leaflet prolapse. The simple and easily reproducible cusp-level shortening procedure consists of plication of the redundant chorda underneath the leaflet. Provided the chorda is thick enough, this procedure is more likely to be applied to regional mitral anterior prolapse due to elongation of the chorda, even in patients with non-rheumatic heart disease. The present patient underwent perioperative adaptive servo-ventilation (ASV) therapy. ASV might help to prevent atrial fibrillation recurrence after the Maze procedure by reducing sympathetic overactivity, contributing to the durability and outcome of mitral valve repair with cusp-level chordal shortening.

Severe Regurgitant Bicuspid Aortic Valve in a Patient with Overlapping Left Ventricular Noncompaction and Asymmetrical Septal Hypertrophy.

Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism.

Symmetrical papillary muscle approximation for functional mitral regurgitation with idiopathic dilated cardiomyopathy.

The cases are reported of mitral valve repair with symmetrical papillary muscle approximation from heads to bases close to cardiac apex for functional mitral regurgitation (FMR). The two papillary heads attaching the chordae to both leaflets from the posteromedial papillary muscle were approximated parallel to the solitary head of the anterolateral papillary muscle. This procedure permits an even reduction of lateral shift of the papillary muscle, resulting in an elimination of mitral tethering, and provides a satisfactory and durable mitral valve repair with good outcomes in patients with idiopathic dilated cardiomyopathy and FMR.

Mid-Term Patency of Spiral Saphenous Vein Graft for Malignant Superior Vena Cava Syndrome.

Reports documenting the mid-term patency of spiral saphenous vein grafts for superior vena cava syndrome in patients with advanced thoracic malignancy are, so far, scarce. The present report describes a 69-year-old man who suffered superior vena cava syndrome due to malignant invasion by advanced lung cancer. Since the huge mass in the anterior mediastinum was unresectable, a bypass from the left innominate vein to the right atrium using an autologous spiral saphenous vein graft was surgically created. Postoperatively, the patient received chemoradiotherapy and maintenance anticoagulant therapy, resulting in survival for 4 years without graft occlusion or recurrence of superior vena cava syndrome.

Phase I trial of gemcitabine dose escalation with concurrent radiotherapy for patients with locally advanced pancreatic cancer.

AIM: The safety and efficacy, and the dose-limiting toxicity (DLT) of the chemotherapeutic agent gemcitabine administered in conjunction with radiotherapy in patients with locally advanced pancreatic cancer are not yet established. Here, we evaluated the safety and efficacy, DLT, and maximum tolerated dose of gemcitabine with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Tumor response and time to progression were also assessed. PATIENTS AND METHODS: Patients with previously untreated pancreatic cancer (n = 12) received gemcitabine intravenously on days 1, 8, and 15. Concurrent radiation therapy was initiated on day 1 (40 Gy in 2 Gy/day x 20 fractions, days 1-5, 8-12, 15-19, 22-26). Patients received limited-field irradiation with three-dimensional radiotherapy. Dose escalation included dose levels 1-3 (gemcitabine 400, 600, and 800 mg/m(2)). RESULTS: No patient developed DLT in this study. Of the 12 patients, there were 11 sustained responses, 0 partial responses, and 1 progressive disease. Two patients with a sustained response underwent surgery after re-evaluation. The median progression-free survival was 8 months, not including the patients that underwent surgery. CONCLUSION: Weekly gemcitabine at a dose of 800 mg/m(2) with concurrent radiation therapy in patients with locally advanced pancreatic cancer was well tolerated. and IAP.

Prognostic factors for survival in patients with recurrent cervical cancer previously treated with radiotherapy.

INTRODUCTION: The aim of this study was to identify the prognostic factors and to establish a model for the prediction of life expectancy in patients with recurrent cervical cancer that had previously been treated with radiotherapy. METHODS: The records of consecutive women with recurrent cervical cancer after radiotherapy were retrospectively reviewed. Primary disease, follow-up, and recurrence data were collected. Univariate and multivariate analyses of prognostic factors of survival were performed. RESULTS: A total of 162 patients were included in our database. The median survival after recurrence was 15 months. Multivariate analysis revealed that symptom status, the site of relapse, prior chemoradiotherapy, and treatment modality were significant prognostic factors in terms of survival after recurrence. Patient survival was inversely correlated with the number of these prognostic factors. When the patients were divided into 3 prognostic groups, (low risk: patients with no poor prognostic factors; intermediate: patients with one poor prognostic factor; and high-risk: patients with more than 2 poor prognostic factors), the patients in the high-risk group had a significantly shorter survival (median, 10 months) than those with one risk factor (median, 20 months) or no risk factors (median, 36 months). CONCLUSIONS: Symptom status, the site of relapse, prior chemoradiotherapy, and treatment modality are significant prognostic factors in patients with recurrent cervical cancer that had previously been treated with radiotherapy. Our prognostic model, composed of 4 clinical variables, may enable physicians to predict survival more accurately.

Concurrent weekly nedaplatin, external beam radiotherapy and high-dose-rate brachytherapy in patients with FIGO stage IIIb cervical cancer: a comparison with a cohort treated by radiotherapy alone.

OBJECTIVES: The aim of this study was to evaluate whether nedaplatin-based concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) is superior to radiotherapy (RT) alone in patients with FIGO stage IIIb cervical cancer. METHODS: The records of 41 consecutive women treated either with nedaplatin-based CCRT using HDR-ICBT (n = 20) or RT alone (nonrandomized control group, n = 21) for stage IIIb cervical cancer were retrospectively reviewed. The activity and toxicity were compared between the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. RESULTS: The 5-year overall survival rates in the CCRT and RT groups were 65 and 33.3%, respectively. The median OS of the CCRT and RT groups were 60 and 29 months, respectively. CCRT was significantly superior to RT alone with regard to PFS (p = 0.0015) and OS (p = 0.0364). The frequency of acute grade 3-4 toxicity was significantly higher in the CCRT group than in the RT group. However, no statistically significant difference was observed with regard to severe late toxicity. CONCLUSIONS: Nedaplatin-based concurrent chemoradiotherapy was safely performed and significantly improved the prognosis of patients with FIGO stage IIIb cervical cancer. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Hybrid Repair for Mega-Aortic Syndrome due to Giant Cell Aortitis in a Heart Failure Patient.

The present report describes a case of mega-aortic syndrome accompanied with severe aortic regurgitation in a 75-year-old man who underwent a two-stage hybrid repair. Intraoperative pathologic findings at the first repair, consisting of Bentall operation and total arch replacement with a Lupiae graft, aided the identification of the giant cell aortitis. Despite complicating hemorrhagic stroke, steroid therapy was initiated and endovascular repair was subsequently completed. Over more than 2 years of follow-up, the patient continued steroid therapy and is doing well without any reintervention.

Efficient eradication of hormone-resistant human prostate cancers by inactivated Sendai virus particle.

Hormone-refractory prostate cancer is one of the intractable human cancers in the world. Here, we examined the direct tumor-killing activity of inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] through induction of Type I interferon (IFN) in the hormone-resistant human prostate cancer cell lines PC3 and DU145. Preferential binding of HVJ-E to PC3 and DU145 over hormone-sensitive prostate cancer cell and normal prostate epithelium was observed, resulting in a number of fused cells. After HVJ-E treatment, a number of IFN-related genes were up-regulated, resulting in Type I IFN production in PC3 cells. Then, retinoic acid-inducible gene-I (RIG-I) helicase which activates Type I IFN expression after Sendai virus infection was up-regulated in cancer cells after HVJ-E treatment. Produced IFN-alpha and -beta enhanced caspase 8 expression via Janus kinases/Signal Transducers and Activators of Transcription pathway, activated caspase 3 and induced apoptosis in cancer cells. When HVJ-E was directly injected into a mass of PC3 tumor cells in SCID (severe combined immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was observed and 85% of the mice became tumor-free. Although co-injection of an anti-asialo GM1 antibody with HVJ-E into each tumor mass slightly attenuated the tumor suppressive activity of HVJ-E, significant suppression of tumor growth was observed even in the presence of anti-asialo GM1 antibody. This suggests that natural killer cell activation made small contribution to tumor regression following HVJ-E treatment in hormone-resistant prostate cancer model in vivo. Thus, HVJ-E effectively targets hormone-resistant prostate cancer by inducing apoptosis in tumor cells, as well as activating anti-tumor immunity.

External-beam radiotherapy for clinically localized prostate cancer in Osaka, Japan, 1995-2006: time trends, outcome, and risk stratification.

PURPOSE: To establish an initial database of external-beam radiotherapy (EBRT) for clinically localized prostate cancer used in Osaka, Japan, and, by analyzing the results of the Osaka multicenter cooperative study, to determine time trends, outcome, and applicability of existing and the authors' original risk stratification methods. PATIENTS AND METHODS: Data of 652 patients with clinically localized prostate cancer (T1-4 N0 M0) were accrued from July to December 2007. These patients had been treated from 1995 through 2006 with consecutive definitive EBRT of > or = 60 Gy at eleven institutions, mainly in Osaka. Altogether, 436 patients were eligible for analysis using several risk stratification methods, namely, those of D'Amico et al., the National Comprehensive Cancer Network (NCCN), and Seattle, as well as the authors' original Prostate Cancer Risk Index (PRIX). RESULTS: The number of patients showed a tenfold increase over 10 years, together with a rapid spread of the use of Gleason Score from 0% to > 90% of cases. The dominant RT dose fractionation was 70 Gy/35 fractions (87%). Hormone therapy had been administered to 95% of the patients and the higher PRIX corresponded to the higher rate of hormone usage. 3- and 5-year biochemical relapse-free survival (bRFS) rates were 85% and 70%, respectively. The D'Amico (p = 0.132), NCCN (p = 0.138), Seattle (p = 0.041) and PRIX (p = 0.044) classifications showed weak or no correlation with bRFS, while the own modified three-class PRIX (PRIX 0, 1-5, 6) showed a strong correlation (p = 0.002). CONCLUSION: The use of prostate EBRT in Japan is still in its infancy, but is rapidly expanding. The short-term outcomes have been satisfactory considering the moderate RT dose. A very high rate of hormone usage may affect the outcome favorably, but also may compromise the usefulness of current risk stratification.

Postoperative concurrent nedaplatin-based chemoradiotherapy improves survival in early-stage cervical cancer patients with adverse risk factors.

OBJECTIVES: The aim of this study was to evaluate the efficacy of postoperative nedaplatin-based concurrent chemoradiotherapy (CCRT) in patients with FIGO stage IA2-IIB cervical cancer with adverse risk factors. METHODS: We retrospectively reviewed the medical records of 183 patients with early-stage cervical cancer who had undergone radical surgery between April 1997 and March 2006. Of these, 68 patients displayed high-risk prognostic factors such as positive pelvic lymph nodes, parametrial involvement, or a positive surgical margin. Fifty-seven patients demonstrated intermediate-risk prognostic factors including deep stromal invasion, capillary lymphatic space involvement, or large tumor diameter. These patients were treated postoperatively with CCRT or radiotherapy alone (RT). Fifty-eight patients showed no risk factors and, therefore, received no adjuvant therapy after surgery. The 3-year recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups. RESULTS: CCRT was significantly superior to RT alone with regard to recurrence rate, PFS, and OS in patients that displayed high-risk and intermediate-risk prognostic factors. The frequencies of acute grade 3-4 toxicities were significantly higher in patients treated with CCRT than in those treated with RT alone. However, no statistically significant difference was observed with regard to severe late toxicities. CONCLUSIONS: Postoperative nedaplatin-based CCRT was safely performed and improved the prognosis of FIGO stage IA2-IIB cervical cancer patients displaying high-risk or intermediate-risk prognostic factors. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Impact of postoperative irradiation after non-curative resection of hilar biliary cancer.

BACKGROUND: The aim of this retrospective study was to determine the effect of surgical margin on the outcome of postoperative radiotherapy (RT) in patients with resected hilar biliary cancer. METHODS: The study subjects were 87 patients with hilar biliary cancer resected surgically before 2008. Based on the Japanese Society of Biliary Surgery (JSBS) criteria for diagnosis of biliary cancer, the surgical margin status was categorized as margin 1 (histopathologically margin negative, but cancer cells identified within 5 mm from the margin), margin 2 (histopathologically margin positive), and margin 0 (other margin status). RESULTS: The surgical margin was 1 or 2 in 44 patients and 21 of these patients underwent RT. The 3-year overall survival and progression-free survival rates of the RT and non-RT groups were 47% and 23% (P = 0.0392), and 49% and 19% (P = 0.0197), respectively. Univariate and multivariate analyses identified RT as the only factor that influenced survival. Subgroup analysis showed that the effect of RT was dependent on pathologically negative lymph node metastasis and positive margin (margin 2). CONCLUSION: Postoperative RT is beneficial for patients with margins 1 and 2, especially those who are lymph node metastasis negative and have histopathologically positive margin.

High-dose-rate interstitial brachytherapy for previously untreated cervical carcinoma.

PURPOSE: The aim of the study was to evaluate the results of high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with advanced cervical carcinoma in which intracavitary radiation therapy may result in a suboptimal dose distribution. METHODS AND MATERIALS: Between 1995 and 2005, 25 patients of median age 64 years were treated with external beam radiation therapy and HDR-ISBT. The International Federation of Gynecology and Obstetrics stages of the patients were I (4%), II (16%), III (68%), and IVA (12%). Whole pelvic irradiation of 30Gy/15 fractions was followed by HDR-ISBT of 30Gy/5 fractions/3 days. Subsequently, additional pelvic external beam radiation therapy of 20Gy/10 fractions was delivered with a midline block. The median followup period was 55 months. RESULTS: The actuarial 5-year progression-free survival and overall survival rates for all cases were 42% and 54%, respectively. For the 17 patients with a Stage III tumor, the 5-year local control and overall survival rates were 73% and 51%, respectively. Two patients (8%) developed late toxicities of Grade 3. CONCLUSIONS: A high rate of pelvic control and survival with acceptable level of late toxicities were obtained for patients with advanced cervical carcinoma treated with HDR-ISBT.

Verification of air-kerma strength of 125I seed for permanent prostate implants in Japan.

BACKGROUND: To assure the physical quality of brachytherapy, we investigated the difference between measured and manufacturer's stated source strengths in a single model SourceTech Medical (STM)1251 (125)I seed. METHODS: A well-type ionization chamber with a single-seed holder was used to measure the source strength of 2412 (125)I seeds before implant in 34 patients. The air-kerma strength was 0.450 U for all cases. The mean source strength for each patient was measured and compared with the manufacturer's stated value. The deviation from the measured value was compared with the tolerance range of the American Association of Physicists in Medicine (AAPM) TG-56 report's recommendation. RESULTS: The measured source strength was higher than the manufacturer's stated value, with a median difference of 1% (range, 2% to 5%). Sixteen of the total of 2412 seeds (0.7%) were more than 5% different from the manufacturer's stated value. The median SD from the mean value was 2.2% (range, 1.1% to 2.5%) for all patients. CONCLUSION: This is the first report of a single-seed assay performed for the model STM1251 (125)I seed. In this study the manufacturer's stated strength agreed well with the measured value. Nevertheless, the advisability of performing a single-seed assay at every institution should be considered, by referring to the appropriate regulations; for example, those used in the United States.

Assessment of influence of smoking, drinking, leukoplakia and dental irritation on local control of early oral tongue carcinoma treated with brachytherapy: age and dental factors are potential prognostic factors.

BACKGROUND: To examine the background characteristics of elderly patients (65 years or older) with node-negative mobile tongue cancer (T1-2N0M0) who showed worse local control than a younger group. MATERIALS AND METHODS: We retrospectively analyzed background data for 265 patients treated with brachytherapy with or without external radiotherapy between 1967 and 1999. We examined dental factors (such as irritation by prosthesis), leukoplakia, tobacco smoking and alcohol consumption for comparisons between the elderly (age > or = 65 years; n = 83) and a control group (64 years or younger; n = 182). RESULTS: The elderly patients showed a worse outcome than the control group (respectively 86% and 70% at 5 years; P < 0.05). Incidence of dental factors tended to be higher for elderly patients (53%) than the control group (40%, P = 0.07). Dental factors proved to have prognostic importance for local control. Five-year local control rate was 85% for patients with and 76% for patients without dental factors (P = 0.04). The elderly group positive for dental factors showed a lower 5-year local control rate (61%) than the other three groups [(elderly without the dental factor (-) group (80%), control with the dental factor (+) group (84%), and control without the dental factor (-) group (87%)] (P < 0.05). Leukoplakia was found more frequently in the control (23%) than in the elderly group (5%) (P = 0.006) but had no effect on treatment outcome. CONCLUSIONS: Age and dental factors (including prosthesis irritation) are potentially important prognostic factors for local control of oral tongue cancer treated with brachytherapy, especially for elderly patients.

Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis.

OBJECTIVE: The incidence of severe graft-vs-host disease (GVHD) in unmanipulated human leukocyte antigen (HLA) 2-3 antigen-mismatched bone marrow transplantation (BMT) using cyclosporine and methotrexate as GVHD prophylaxis is 80% to 90%. We investigated whether pharmacological GVHD prophylaxis consisting of four drugs, including a steroid, effectively suppressed GVHD in this transplantation setting. MATERIALS AND METHODS: Thirty patients who had hematologic malignancies at an advanced stage or with poor prognosis underwent allogeneic BMT using a myeloablative preconditioning regimen consisting of cyclophosphamide (60 mg/kg x 2), total body irradiation (8-10 Gy), and fludarabine (30 mg/m(2) x 4) with or without cytosine arabinoside (2 g/m(2) x 4), and GVHD prophylaxis consisting of a combination of tacrolimus, methotrexate, mycophenolate mofetil, and methylprednisone (2 mg/kg). Early therapeutic intervention for GVH reaction or grade I GVHD was performed, and steroid was slowly tapered. RESULTS: All patients achieved donor-type engraftment. Neutrophil (>0.5 x 10(9)/L) and platelet (>20 x 10(9)/L) engraftment was achieved on day 13 and on day 30, respectively. Seventeen patients (56.7%) had no GVHD. Eleven patients (36.7%) developed grade II-III acute GVHD. Seven patients (23.3%) died of transplant-related toxicity, including fungal or viral infections and thrombotic microangiopathy, and four patients died of disease progression. Estimated relapse rate at 3 years was only 20.9%. The probability of survival at 3 years was 49.9%. CONCLUSIONS: These data suggest that, in unmanipulated HLA-haploidentical allogeneic BMT, this GVHD prophylactic regimen, which includes methylprednisolone 2 mg/kg, and early therapeutic intervention for GVH reaction suppress the incidence of severe GVHD to an acceptable level, while preserving the graft-vs-leukemia effect.

Insulin-like growth factor stimulation increases radiosensitivity of a pancreatic cancer cell line through endoplasmic reticulum stress under hypoxic conditions.

Tumor hypoxia is an obstacle to radiotherapy. Radiosensitivity under hypoxic conditions is determined by molecular oxygen levels, as well as by various biological cellular responses. The insulin-like growth factor (IGF) signaling pathway is a widely recognized survival signal that confers radioresistance. However, under hypoxic conditions the role of IGF signaling in radiosensitivity is still poorly understood. Here, we demonstrate that IGF-II stimulation decreases clonogenic survival under hypoxic conditions in the pancreatic cancer cell lines AsPC-1 and Panc-1, and in the human breast cancer cell line MCF-7. IGF treatment under hypoxic conditions suppressed increased radiation sensitivity in these cell lines by pharmacologically inhibiting the phosphoinositide 3-kinase-mammalian target of rapamycin pathway, a major IGF signal-transduction pathway. Meanwhile, IGF-II induced the endoplasmic reticulum stress response under hypoxia, including increased protein levels of CHOP and ATF4, mRNA levels of CHOP, GADD34, and BiP, as well as splicing levels of XBP-1. The response was suppressed by inhibiting phosphoinositide 3-kinase and mammalian target of rapamycin activity. Overexpression of CHOP in AsPC-1 cells increased radiation sensitivity by IGF-II simulation under hypoxic conditions, whereas suppression of CHOP expression levels with small hairpin RNA or a dominant negative form of a proline-rich extensin-like receptor protein kinase in hypoxia decreased IGF-induced radiosensitivity. IGF-induced endoplasmic reticulum stress contributed to radiosensitization independent of cell cycle status. Taken together, IGF stimulation increased radiosensitivity through the endoplasmic reticulum stress response under hypoxic conditions.