Successful Treatment of Whole Coronary Artery Spasm after Off-Pump Coronary Artery Bypass Grafting.

Coronary artery spasm after coronary artery bypass grafting is a rare but life-threatening condition. Herein, we report the case of a 77-year-old man who received off-pump coronary artery bypass grafting. An hour after surgery, there was a sudden hemodynamic compromise due to coronary artery spasm, prompting emergent coronary angiography with extracorporeal membrane oxygenation support. Because the angiography results showed diffuse severe spasm of the entire native coronary artery, the patient was treated with an intracoronary injection of vasodilators. The patient recovered in 7 days with mechanical support, catecholamines, and vasodilators, and he was discharged on postoperative day 30. Although coronary artery spasm after off-pump coronary artery bypass surgery is a rare condition, it must be suspected when sudden circulatory collapse occurs.

Two-stage hybrid repair with over-the-scope clip for atrioesophageal fistula after catheter-based ablation.

In this report, we present a case in which we successfully performed two-stage hybrid repair of heart surgery and endoscopic treatment with over-the-scope-clip system for atrio-esophageal fistula after catheter based ablation.

Phase I study of aflibercept in combination with docetaxel in Japanese patients with advanced solid malignancies.

Angiogenesis is a hallmark of cancer development. This study sought to determine the recommended dose of aflibercept, a recombinant fusion protein targeting VEGF-A, VEGF-B and placental growth factor (PlGF), combined with docetaxel in Japanese patients with advanced solid malignancies. This phase I study was planned to include 12 patients following a 3 + 3 algorithm to determine the maximum tolerated dose of aflibercept combined with docetaxel in patients with metastatic or unresectable solid tumors (trial registration: NCT00545246). Docetaxel (75 mg/m2 every 3 weeks or 60 mg/m2 after protocol amendment) was combined with escalating doses of aflibercept (2, 4 and 6 mg/kg every 4 weeks). Free and VEGF-bound aflibercept were measured to assess free aflibercept in excess of the VEGF-bound form. At the starting dose of the combination, 3 of 6 patients treated experienced febrile neutropenia. After reducing the docetaxel dose to 60 mg/m2 in step 2 and permitting therapeutic granulocyte colony-stimulating factor (G-CSF) use, 2 of 3 patients in both cohorts experienced febrile neutropenia. Five patients (42%) had a partial response and 4 patients had stable disease (33%). Free aflibercept in excess of the VEGF-bound form was not maintained at this dose level. The dose limiting toxicity (DLT) of aflibercept combined with docetaxel was febrile neutropenia, which occurred in 2 of 3 Japanese patients at the lowest aflibercept dose level (2 mg/kg) combined with docetaxel (60 mg/m2) and therapeutic G-CSF use. A recommended dose for further studies was not determined because of the DLT at the starting dose.

Surgical and multitreatment approach in a case of primary cardiac angiosarcoma: A case report.

INTRODUCTION AND IMPORTANCE: Primary cardiac angiosarcoma is extremely rare, and its prognosis remains poor, with a mean life expectancy of only a few months. Here, we report a case of primary cardiac angiosarcoma. CASE PRESENTATION: A 49-year-old Japanese woman with a month-long history of dyspnea was admitted to our hospital for pericardial effusion. Chest computed tomography and cardiac magnetic resonance imaging showed a mass in the right atrium. The patient underwent surgical resection of the tumor, and the pathological diagnosis was angiosarcoma. The patient received radiotherapy after surgery. Six months following surgery, she underwent chemotherapy following the diagnosis of lung metastasis. The patient died 18 months after the initial diagnosis. CLINICAL DISCUSSION: Cardiac angiosarcoma is rare and difficult to diagnose early because it is associated with few symptoms. Moreover, there are currently no established guidelines for the treatment of this disease because of its rarity and sparse descriptive literature Therefore, multidisciplinary therapies should be considered, including surgery, radiotherapy, and chemotherapy. CONCLUSION: There is no standard treatment for cardiac angiosarcoma, but surgical resection, chemotherapy, radiation therapy, or a combination of these therapies may be useful.

Comprehensive analysis of the associations between clinical factors and outcomes by machine learning, using post marketing surveillance data of cabazitaxel in patients with castration-resistant prostate cancer.

BACKGROUND: We aimed to evaluate relationships between clinical outcomes and explanatory variables by network clustering analysis using data from a post marketing surveillance (PMS) study of castration-resistant prostate cancer (CRPC) patients. METHODS: The PMS was a prospective, multicenter, observational study of patients with metastatic, docetaxel-refractory CRPC treated with cabazitaxel in Japan after its launch in 2014. Graphical Markov (GM) model-based simulations and network clustering in 'R' package were conducted to identify correlations between clinical factors and outcomes. Factors shown to be associated with overall survival (OS) in the machine learning analysis were confirmed according to the clinical outcomes observed in the PMS. RESULTS: Among the 660 patients analyzed, median patient age was 70.0 years, and median OS and time-to-treatment failure (TTF) were 319 and 116 days, respectively. In GM-based simulations, factors associated with OS were liver metastases, performance status (PS), TTF, and neutropenia (threshold 0.05), and liver metastases, PS, and TTF (threshold 0.01). Factors associated with TTF were OS and relative dose intensity (threshold 0.05), and OS (threshold 0.01). In network clustering in 'R' package, factors associated with OS were number of treatment cycles, discontinuation due to disease progression, and TTF (threshold 0.05), and liver and lung metastases, PS, discontinuation due to adverse events, and febrile neutropenia (threshold 0.01). Kaplan-Meier analysis of patient subgroups demonstrated that visceral metastases and poor PS at baseline were associated with worse OS, while neutropenia or febrile neutropenia and higher number of cabazitaxel cycles were associated with better OS. CONCLUSIONS: Neutropenia may be a predictive factor for treatment efficacy in terms of survival. Poor PS and distant metastases to the liver and lungs were shown to be associated with worse outcomes, while factors related to treatment duration were shown to positively correlate with better OS.

Surgical Strategy for Huge Right Coronary Artery Aneurysm Combined with Left Ventricular Fistula.

Coronary artery aneurysms combined with left ventricular fistulas are rare; coronary revascularization strategy after coronary artery aneurysm resection is complex in such cases. We report the surgical repair of a giant right coronary artery aneurysm with a fistula in the left ventricle in a 79-year-old woman diagnosed with an aneurysm 50 mm in diameter. Surgical repair included resection of the coronary artery aneurysm, coronary artery bypass grafting to the posterior descending artery, and isolation of reconstructed right coronary circulation from the fistula. The postoperative course was uneventful; postoperative coronary angiography revealed a patent bypass graft unconnected to the left ventricle.

Left Ventricular Outflow Tract Obstruction of Double Valve Re-Replacement Using Bioprosthesis.

We present a case of left ventricular outflow tract (LVOT) obstruction after double valve re-replacement with bioprostheses. A 72-year-old man, who had undergone double valve replacement (DVR) with bioprosthetic valves 9 years previously, underwent re-replacement of valves because of structural valve deterioration. However, owing to LVOT obstruction related to the bioprosthesis in the mitral position, acute pulmonary edema occurred immediately after surgery. LVOT obstruction was diagnosed by emergent cardiac catheterization. So prompt re-replacement surgery using a mechanical prosthesis was performed.

Phase I dose-escalation study of the safety, tolerability, and pharmacokinetics of aflibercept in combination with S-1 in Japanese patients with advanced solid malignancies.

Background Aflibercept, a recombinant fusion protein binding VEGF-A, VEGF-B and placental growth factor, inhibits tumor growth by blocking angiogenesis. The aim of this phase I dose-escalation study was to determine the recommended phase II dose (RP2D) of aflibercept in combination with S-1 in Japanese patients with solid tumors. Patients and methods Sequential cohorts of 3-6 patients with metastatic or unresectable solid tumors, who had failed at least one prior line of standard treatment or who were not suitable for such treatment, were to receive escalating doses of aflibercept every 2 weeks, starting at 2 mg/kg, combined with S-1 at 40 mg/m2 twice daily (80 mg/m2/day; 4 weeks on/2 weeks off). Dose-escalation was to be based on the incidence of dose-limiting toxicity (DLT). Blood samples were collected for pharmacokinetic analysis. Results At the first dose level (aflibercept 2 mg/kg plus S-1) 1 of 6 patients experienced a DLT (grade 4 proteinuria). The aflibercept dose was consequently escalated to 4 mg/kg; 1 of 3 patients treated at this dose level had a DLT (grade 2 pleural effusion), and another patient experienced grade 3 reversible posterior leukoencephalopathy syndrome after the DLT assessment period. Additional patients were therefore enrolled into the first dose level to explore safety and tolerability. The study was subsequently terminated prematurely. The maximum tolerated dose was not reached and the RP2D was not determined in Japanese patients. Conclusions The tolerability and safety of aflibercept 2 mg/kg in combination with S-1 was confirmed in Japanese patients with advanced solid tumors.

Extreme Elevation of the Prothrombin Time-International Normalized Ratio due to a Probable Interaction between Warfarin and Flutamide.

Flutamide, a chemotherapeutic agent for prostate cancer, is known to enhance warfarin anticoagulation. However, not much is known about its pharmaceutical interaction. We herein report the case of a patient with an implanted pacemaker for atrial fibrillation with bradycardia who was on warfarin. This patient presented with deterioration of hematuria, gingival, ear, and subcutaneous bleeding. The prothrombin time-international normalized ratio was extremely elevated after starting flutamide to treat progression of prostate cancer. Fatal bleeding complications were able to be prevented by the immediate administration of prothrombin complex concentrate, but the effect of flutamide on warfarin was prolonged for about two more weeks after the withdrawal of flutamide.

A functional evaluation of cerebral perfusion for coronary artery bypass grafting patients.

We evaluate the utility of providing a pulsatile blood flow by applying off-pump coronary artery bypass grafting (CABG) or intra-aortic balloon pumping (IABP) with conventional CABG to prevent perioperative stroke in patients with cerebral hypoperfusion on single-photon emission-computed tomography (SPECT). A total of 286 patients underwent isolated CABG with a cerebral magnetic resonance angiography (MRA) evaluation between 2006 and 2015. Seventy-five had significant stenosis and/or occlusion of craniocervical vessels; the other 211 had no significant stenosis. Cerebral SPECT was performed for 49 (SPECT group) of the 75 patients. The SPECT group was further divided into a normal perfusion (NP) (n = 37); and a hypoperfusion (HP) (n = 12). In the present study we compared the NP group and the 211 patients with no significant stenosis (as a control group) to the HP group. No strokes occurred in the HP group, and 1 stroke occurred at the time of operation in the control group. Postoperative stroke within 30 days occurred in 3 patients in the control group; the difference was not statistically significant. The long-term stroke-free rates of the HP and Control group did not differ to a statistically significant extent. The functional evaluation of cerebral perfusion by SPECT is important when patients have significant stenotic lesions on cerebral MRA. Maintaining an adequate pulsatile flow by off-pump CABG or IABP with conventional CABG will help prevent perioperative stroke, even if cerebral hypoperfusion is detected by SPECT.

Metabolic Profiling of Fish Meat by GC-MS Analysis, and Correlations with Taste Attributes Obtained Using an Electronic Tongue.

To evaluate the taste of ordinary muscle from white-fleshed fish, we used GC-MS metabolomic analysis to characterise the compounds therein, and correlated the obtained data with taste measurements from an electronic tongue. Prediction models using orthogonal partial least squares were produced for different taste attributes, and the primary metabolic components correlated with the taste attributes were identified. Clear differences were observed in the component profiles for different fish species. Using an electronic tongue, differences in tastes were noted among the fish species in terms of sourness, acidic bitterness, umami and saltiness. The obtained correlations allowed the construction of good taste prediction models, especially for sourness, acidic bitterness and saltiness. Compounds such as phosphoric acid, lactic acid and creatinine were found to be highly correlated with some taste attributes. Phosphoric acid in particular showed the highest variable important for prediction (VIP) scores in many of the taste prediction models, and it is therefore a candidate marker to evaluate the tastes of white-fleshed fish.

Pericardial Sandwich Technique for End-to-End Anastomosis of Artificial Graft.

End-to-end anastomosis between prosthetic grafts seems technically easy; however, bleeding from the needle hole or at the site of anastomotic discrepancy can be problematic. The pericardial sandwich technique helps to resolve this issue. The grafts are generally anastomosed to each other with a continuous suture, and a strip of autopericardium is sandwiched circumferentially between the two grafts. Although this anastomosis involves a special technique, it is not intricate. The pericardium effectively covers the needle hole and gap between the grafts. This method is useful for large-vessel surgery, especially in patients with coagulopathy.

Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials.

OBJECTIVES: To evaluate efficacy/safety of baricitinib for rheumatoid arthritis (RA) in Japanese subpopulations from four phase 3 studies, and assess whether results in these subpopulations are consistent with the overall study populations. METHODS: Subgroup analyses (394 patients) of four phase 3 randomized controlled trials: RA-BEGIN [no or limited treatment with disease-modifying antirheumatic drugs (DMARDs)], RA-BEAM [inadequate response (IR) to methotrexate], RA-BUILD [IR to conventional synthetic DMARDs (csDMARDs)], and RA-BEACON (IR to tumor necrosis factor inhibitors receiving csDMARDs). RESULTS: For American College of Rheumatology 20% improvement (ACR20) response rate, Japanese patients receiving baricitinib 4-mg showed similar improvement compared to methotrexate at Week 24 (72 versus 69%; RA-BEGIN), and greater improvement compared with placebo at Week 12 (67 versus 34%; RA-BEAM). Japanese patients receiving baricitinib 4-mg also showed greater improvement compared with placebo at Week 12 in RA-BUILD and RA-BEACON. Across all studies, baricitinib was well-tolerated, with no deaths and one malignancy. In RA-BEGIN and RA-BEAM, herpes zoster rates were higher for Japanese patients than for overall populations; all events were mild/moderate. CONCLUSION: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations. Baricitinib appears to be similarly effective in Japanese patients.

[Intra-operative Acute Aortic Dissection during Aortic Root Reimplantation and Mitral Valve Reconstruction Surgery in a Patient with Marfan Syndrome;Report of a Case].

In patients with Marfan syndrome, cardiovascular complication due to aortic dissection represents the primary cause of death. Iatrogenic acute aortic dissection during cardiac surgery is a rare, but serious adverse event. A 51-year-old woman with Marfan syndrome underwent elective aortic surgery and mitral valve reconstruction surgery for the enlarged aortic root and severe mitral regurgitation. We replaced the aortic root and ascending aorta based on reimplantation technique. During subsequent mitral valve reconstruction, we found the heart pushed up from behind. Trans-esophageal echocardiography revealed a dissecting flap in the thoracic descending aorta. There was just weak signal of blood flow in the pseudolumen. We did not add any additional procedures such as an arch replacement. Cardio-pulmonary bypass was successfully discontinued. After protamine sulfate administration and blood transfusion, blood flow in the pseudolumen disappeared. The patient was successfully discharged from the hospital on 33th postoperative day without significant morbidities.

Assessing responses of the Hiroshima Bay ecosystem to increasing or decreasing phosphorus and nitrogen inputs.

The Japanese Government is seeking an appropriate level of nutrient load from the land to maintain the highest possible estuarine fishery production and water transparency simultaneously. To provide a scientific basis for the governmental inquiry, we conducted sensitivity analyses using an ecosystem model of Hiroshima Bay in order to assess the ecosystem's responses to phosphorus and nitrogen inputs. Load levels of phosphorus (Case P), nitrogen (Case N) and both phosphorus and nitrogen (Case NP) that were different from the average loading recorded during 1991-2000 (±25%, ±50%, and ±75%) were applied. The results showed that phosphorus had a significantly greater impact on the primary production of the bay than nitrogen. Case P+25 increased the primary production but led to N-limitation. However, it was found that Case NP at the levels over +25% could bring the Hiroshima Bay ecosystem back to its eutrophic state of 30 years ago.

Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04-.

BACKGROUND: In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin. METHODS: Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1-15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m(2), the second dose (level 2) was 20 mg/m(2), and the third dose (level 3) was 25 mg/m(2). Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1-29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned. RESULTS: Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m(2)) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m(2)) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response. CONCLUSIONS: In this phase I trial, RD of cisplatin was identified as 20 mg/m(2). Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach. TRIAL REGISTRATION: UMIN000008941.

Two-stage operation for isolated pulmonary valve infectious endocarditis with Candida parapsilosis.

We report a case of isolated pulmonary infectious endocarditis (IE) with Candida parapsilosis. A 66-year-old man presented with fever and cough. Echocardiography showed severe pulmonary regurgitation and vegetations on the pulmonary valves. Initially, antibiotics were prescribed against bacterial IE, and the vegetations disappeared; however, the pulmonary vegetations relapsed, and C. parapsilosis was grown from blood cultures. We performed a debridement without a pulmonary valve replacement. There was no recurrence of IE for 3 years, and then the patient developed right ventricular enlargement and severe tricuspid regurgitation due to severe pulmonary regurgitation. Pulmonary valve replacement was performed. Now the patient is free from infection.

Detection of esophageal fiducial marker displacement during radiation therapy with a 2-dimensional on-board imager: analysis of internal margin for esophageal cancer.

PURPOSE: To quantify the interfraction displacement of esophageal fiducial markers for primary esophageal cancer radiation therapy. METHODS AND MATERIALS: Orthogonal 2-dimensional (2D) matching records fused to vertebrae were analyzed in clinically staged T1/2N0 esophageal cancer patients undergoing endoscopic clipping as fiducial metal markers. Displacement of the markers between the digitally reconstructed radiographs and on-board kilovoltage images during radiation therapy was analyzed according to direction and esophageal site. RESULTS: Forty-four patients, with 81 markers (10 proximal, 42 middle, and 29 distal), underwent 367 2D matching sessions during radiation therapy. The mean (SD) absolute marker displacement was 0.26 (0.30) cm in the right-left (RL), 0.50 (0.39) cm in the superior-inferior (SI), and 0.24 (0.21) cm in the anterior-posterior (AP) direction. Displacement was significantly larger in the SI than in the RL and AP directions (P<.0001). In the SI direction, mean absolute displacements of the distal, middle, and proximal esophagus were 0.67 (0.45) cm, 0.42 (0.32) cm, and 0.36 (0.30) cm, respectively. Distal esophagus displacement was significantly larger than those of the middle and proximal esophagus (P<.0001). The estimated internal margin to cover 95% of the cases was 0.75 cm in the RL and AP directions. In the SI direction, the margin was 1.25 cm for the proximal and middle esophagus and 1.75 cm for the distal esophagus. CONCLUSIONS: The magnitude of interfraction displacement of esophageal clips was larger in the SI direction, particularly in the distal esophagus, but substantial displacement was observed in other directions and at other esophageal sites. It is practical to take estimated movements into account with internal margins, even if vertebrae-based 2D matching is performed.

[Chemoradiotherapy for advanced gastric cancer].

In the US and Europe, chemoradiotherapy has become a standard treatment not only for head and neck cancer, esophageal cancer, pancreatic cancer, and rectal cancer, but also for gastric cancer. In particular, chemoradiotherapy has been established as an adjuvant therapy. In Japan, it has not been established as a standard treatment. Its indications are limited, and it is often performed as palliative care. Disadvantages of radiation therapy for gastric cancer include the difficulty of establishing the area to irradiate due to peristaltic movement, risk of perforation and ulceration from high-dose radiation, and ineffectiveness against adenocarcinoma with low radiosensitivity. In recent years, technological advancement of radiation therapy has enabled pinpoint accuracy in the treatment of primary gastric lesions and regional lymph nodes. There has been much anticipation that chemoradiotherapy will become a part of multidisciplinary treatment for advanced cancer. This report describes the current state of chemoradiotherapy for gastric cancer in Japan and overseas, and outlines our approach to locally advanced gastric cancer.

Predicting pubic arch interference in prostate brachytherapy on transrectal ultrasonography-computed tomography fusion images.

We investigated the usefulness of the fusion image created by transrectal ultrasonography (TRUS) and large-bore computed tomography (CT) for predicting pubic arch interference (PAI) during prostate seed brachytherapy. The TRUS volume study was performed in 21 patients, followed by large-bore computed tomography of patients in the lithotomy position. Then, we created TRUS-CT fusion images using a radiation planning treatment system. TRUS images in which the prostate outline was the largest were overlaid on CT images with the narrowest pubic arch. PAI was estimated in the right and left arch separately and classified to three grades: no PAI, PAI positive within 5 mm and PAI of >5 mm. If the estimated PAI was more than 5 mm on at least one side of the arch, we judged there to be a significant PAI. Brachytherapy was performed in 18 patients who were evaluated as not having significant PAI on TRUS. Intra-operative PAI was observed in one case, which was also detected with a fusion image. On the other hand, intra-operative PAI was not observed in one case that had been evaluated as having significant PAI with a fusion image. In the remaining three patients, TRUS suggested the presence of significant PAI, which was also confirmed by a fusion image. Intra-operative PAI could be predicted by TRUS-CT fusion imaging, even when it was undetectable by TRUS. Although improvement of the reproducibility of the patients' position to avoid false-positive cases is warranted, TRUS-CT fusion imaging has the possibility that the uncertainty of TRUS can be supplemented.