Publications by authors named "Takahiko Sakamoto"

71 Publications

Pretreatment neutrophil-to-lymphocyte ratio predicts treatment efficacy and prognosis of cytotoxic anticancer drugs, molecular targeted drugs, and immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.

Transl Lung Cancer Res 2021 Jan;10(1):221-232

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo, Japan.

Background: Neutrophil-to-lymphocyte ratio (NLR) has recently attracted attention as a prognostic predictor in patients with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors (ICIs). However, the utility of NLR in relation to cytotoxic anticancer drugs or molecular targeted drugs remains unclear. We determined if NLR could predict the treatment efficacy and prognosis in NSCLC patients who receive cytotoxic anticancer drugs or molecular targeted drugs, as well as ICIs, in a cross-sectional manner.

Methods: Of 658 patients with advanced NSCLC who received first-line systemic treatment in our hospital between 2008 and 2019, 312 who met the analytical criteria were included in the study. We retrospectively analyzed the ability of NLR with a cut-off value of 5 to predict time to treatment failure (TTF) and overall survival (OS) in patients who received the following treatments: first-line treatment with molecular targeted drugs (mt group, n=100); first-line treatment with cytotoxic anticancer drugs (wt group, n=212); and first-line treatment with cytotoxic anticancer drugs followed by ICIs (ICI group, n=58).

Results: In the high- and low-NLR mt subgroups, median TTFs were 6.7 and 14.9 months (P<0.01), respectively, and median survival times (MSTs) were 17.8 and 39.1 months (P<0.01), respectively. In the high- and low-NLR wt subgroups, median TTFs were 1.5 and 5.8 months (P<0.01), and MSTs were 6.3 and 20.7 months (P<0.01), respectively. In the high- and low-NLR ICI subgroups, median TTFs were 1.3 and 6.8 months (P<0.01), and MSTs were 9.2 and 25.8 months (P<0.01), respectively. Multivariate analysis identified NLR as a significant independent predictor of TTF [hazard ratio (HR) 1.89, P=0.01; HR 2.51, P<0.01; and HR 5.06, P<0.01 in the mt, wt, and ICI groups, respectively) and OS (HR 3.81, P<0.01; HR 2.59, P<0.01; and HR 2.48, P<0.01, respectively).

Conclusions: This study showed that NLR might be a predictor of treatment efficacy and prognosis in advanced NSCLC patients who receive various systemic treatments. This finding of consistent applicability of NLR to a wide variety of systemic treatments is of great significance.
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http://dx.doi.org/10.21037/tlcr-20-777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867774PMC
January 2021

Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non-small cell lung cancer.

Cancer Sci 2021 Apr 24;112(4):1506-1513. Epub 2021 Feb 24.

The Jikei University School of Medicine, Tokyo, Japan.

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non-small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post-marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD.
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http://dx.doi.org/10.1111/cas.14715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019226PMC
April 2021

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.

Cancer Sci 2021 Apr 24;112(4):1495-1505. Epub 2021 Feb 24.

The Jikei University School of Medicine, Tokyo, Japan.

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.
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http://dx.doi.org/10.1111/cas.14710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019215PMC
April 2021

Importance and Difficulty of Differentiating BMA-induced AFF Prodromal Symptoms from Hormonal Therapy-related Femoral Pain.

Intern Med 2020 Mar 22;59(6):855-857. Epub 2019 Nov 22.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Japan.

We herein report a case of breast cancer in a 74-year-old woman treated with exemestane as fourth-line hormonal therapy and bone-modifying agents for long time. She suddenly developed a right femoral shaft fracture during treatment. Her femoral fracture had a beaking sign on radiogram. Given this finding, her fracture was ultimately diagnosed as atypical femoral fracture (AFF). In this case, it was difficult to recognize the difference between groin pain as a prodromal symptom of AFF and that due to an adverse reaction to hormonal therapy. Therefore, clinicians should recognize the difficulty of this differentiation and consider the situation with caution.
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http://dx.doi.org/10.2169/internalmedicine.3157-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118384PMC
March 2020

Radiologic features of pneumonitis associated with nivolumab in non-small-cell lung cancer and malignant melanoma.

Future Oncol 2019 Jun 25;15(16):1911-1920. Epub 2019 Apr 25.

The Jikei University School of Medicine, Tokyo, Japan.

To assess the clinical features/imaging characteristics of pneumonitis reported during nationwide nivolumab postmarketing surveillance in Japan. Clinical and radiological data were collected from pneumonitis cases reported during/after nivolumab treatment for melanoma or non-small-cell lung cancer. The expert central review committee evaluated each case. Among 144 cases analyzed, 91 (63.2%) had radiological patterns considered typical for drug-induced pneumonitis and 53 (36.8%) patients had previously unobserved patterns with one or more atypical features, including 23 cases (16.0%) with ground glass opacity confined to the area around the tumor (peritumoral infiltration). A higher proportion of patients with (vs without) peritumoral infiltration had an antitumor response to nivolumab. Images of nivolumab-induced pneumonitis showed previously unobserved radiological patterns.
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http://dx.doi.org/10.2217/fon-2019-0102DOI Listing
June 2019

Neo-aortic insufficiency late after staged reconstruction for hypoplastic left heart syndrome: impact of differences in initial palliative procedures.

Heart Vessels 2019 Sep 27;34(9):1456-1463. Epub 2019 Mar 27.

Department of Pediatric Cardiology, Nagano Children's Hospital, Nagano, Japan.

The neo-aortic insufficiency in patients with hypoplastic left heart syndrome is an important sequela. We assessed the risks of the neo-aortic valve deterioration by the difference of initial palliations: Group I underwent primary Norwood (Nw) with systemic-to-pulmonary artery shunt (SPS), Group II underwent bilateral pulmonary artery banding (bPAB) and subsequent Nw with SPS (bPAB-Nw/SPS), Group III underwent bPAB and subsequent Nw with bidirectional Glenn (BDG) procedure (bPAB-Nw/BDG). The neo-aortic valve z score changes over time did not reach statistical significance in all groups (p = 0.43 for Group I, 0.20 for Group II, and 0.30 for Group III). The degree of neo-aortic valve insufficiency did not change significantly over time during this period except for Group III (p = 0.34 for Group I, 0.20 for Group II, and 0.02 for Group III). On the other hand, dimensions of the neo-aortic annulus and degrees of neo-aortic insufficiency did not differ significantly among the 3 groups at any pre-determined time. The presence or absence of incision into the sino-tubular junction at Nw did not affect the late neo-aortic valve z score or insufficiency. These data indicate that the difference of initial palliative procedures does not affect late neo-aortic valve insufficiency in Nw survivors. Because valve failure may develop in longer follow-up, further observation should be conducted.
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http://dx.doi.org/10.1007/s00380-019-01376-3DOI Listing
September 2019

Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy.

Case Rep Oncol 2019 Jan-Apr;12(1):91-97. Epub 2019 Jan 21.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

In lung cancer, several potential mechanisms of intrinsic and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been explored, including mesenchymal-epithelial transition factor (MET) signaling pathway activation. On the other hand, vascular endothelial growth factor (VEGF) production of EGFR-mutated lung cancer cells is stimulated by predominantly activated MET signaling pathway. Therefore, the inhibition of VEGF axis as the downstream target of MET signaling pathway seems promising. Here, for the first time, we report the potential efficacy of combination therapy with bevacizumab and erlotinib in an EGFR-mutated NSCLC patient with MET amplification who showed intrinsic resistance to initial EGFR-TKI therapy. The patient was a 60-year-old male smoker, showing performance status (PS) 2, who presented with stage IV lung adenocarcinoma (cT4N2M1a) harboring the EGFR exon 19 deletion mutation. He was started on gefitinib at 250 mg/day. However, by 28 days, his symptoms further deteriorated along with the increased tumor size, resulting in PS 3. Then, repeat biopsy was performed, showing the positive MET amplification and the preserved EGFR exon 19 deletion mutation. Therefore, on the basis of the potential efficacy for activated MET signaling pathway as well as the confirmed safety by the known phase II trial for EGFR-mutated patients, the patient was started on combination therapy with bevacizumab at 15 mg/kg every 3 weeks plus erlotinib at 150 mg/day. By 21 days, his symptoms gradually improved along with the decreased tumor size, resulting in better PS with no severe toxicities.
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http://dx.doi.org/10.1159/000493088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381877PMC
January 2019

Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush.

Case Rep Oncol 2019 Jan-Apr;12(1):84-90. Epub 2019 Jan 21.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.
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http://dx.doi.org/10.1159/000493256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381921PMC
January 2019

Significance of Earlier Initiation of Chemotherapy for Lung Cancer Complicated with Primary or Secondary Nephrotic Syndrome following Its Appropriate Differential Diagnosis.

Case Rep Oncol 2019 Jan-Apr;12(1):53-58. Epub 2019 Jan 11.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

We encountered a case of primary lung cancer complicated with membranous nephropathy as primary nephrotic syndrome. Because treatment approaches vary greatly for primary and secondary nephrotic syndrome, a renal biopsy was performed for diagnosis. Much time was required to make a definitive diagnosis of primary nephrotic syndrome, as opposed to paraneoplastic nephrotic syndrome. Consequently, the subsequent chemotherapy was ineffective and caused significant toxicity due to reduced performance status (PS) and progression of hypoalbuminemia. Therefore, it is imperative that a diagnosis be made and treatment be initiated without delay before PS declines and hypoalbuminemia progresses.
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http://dx.doi.org/10.1159/000493851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381920PMC
January 2019

Successful Treatment with Taxane-Based Chemotherapy in Advanced Sebaceous Carcinoma: A Case Report and Literature Review.

Case Rep Oncol 2019 Jan-Apr;12(1):47-52. Epub 2019 Jan 11.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

For sebaceous carcinoma (SC), a rare malignant tumor, no standard chemotherapy regimen for patients with distant metastasis has been studied. We experienced a case of eyelid SC with multiple lung metastases that responded to combination chemotherapy with carboplatin and paclitaxel with 11-month progression-free survival (PFS). This patient also responded to second-line treatment with docetaxel, another taxane, with 7-month PFS, resulting in at least 18 months of survival at the time of reporting. This report shows that taxane-based chemotherapy may be effective for advanced SC, for which no standard therapy has been established.
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http://dx.doi.org/10.1159/000493850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381883PMC
January 2019

A Successful Case of External Stenting for Bronchomalacia Lasting Over 20 Years.

Ann Thorac Surg 2019 08 1;108(2):e103-e104. Epub 2019 Feb 1.

Department of Cardiovascular Surgery, Matsudo City General Hospital, Matsudo, Japan.

We report on a patient with perimembranous ventricular septal defect and pulmonary hypertension. He underwent pulmonary artery banding followed by external stenting of the left bronchus because of secondary bronchomalacia. The external stent applied was a ringed expanded polytetrafluoroethylene graft, 10 mm in diameter and fixed at 8 points. Intracardiac repair was performed at the age of 2 years and the external stent was left in place. Since then, the patient has been healthy and computed tomography reveals that the external stent graft has retained function for over 20 years.
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http://dx.doi.org/10.1016/j.athoracsur.2018.12.055DOI Listing
August 2019

Long-term outcomes of Ross and Ross-Konno operations in patients under 15 years of age.

Gen Thorac Cardiovasc Surg 2019 May 13;67(5):420-426. Epub 2018 Nov 13.

Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo, 162-8666, Japan.

Objective: The Ross operation is an excellent surgical option for young children, regardless of aortic pathology type. However, failure rates are concerning during the second postoperative decade. We sought to determine the predictors of long-term outcomes after Ross and Ross-Konno operation performed in childhood.

Methods: We performed 34 Ross and 9 Ross-Konno operations in pediatric patients (age < 15 years) from 1996 to 2016, and retrospectively evaluated the long-term results.

Results: The postoperative follow-up period was 13.5 ± 3.9 years. In the Ross group, there were one inpatient death and one death after discharge. There were no inpatient deaths in the Ross-Konno group. There were 6 reoperations in the Ross group and 1 in the Ross-Konno group for left ventricular outflow tract (LVOT). Cumulative survival rates were 96.8% and 100% in the Ross and Ross-Konno groups, respectively. The reoperation free rate for LVOT /RVOT (right ventricular outflow tract) were 98.6/85.5% and 91.9/63.4% in the 5th and 10th years of follow-up, respectively. Patients who underwent the operations at age > 8.6 years had higher risks of reoperation for LVOT. Aortic annulus measurements > 24 mm or aorta/pulmonary artery diameter (Ao/PA) ratios > 1.2 conferred higher risks of reoperation for LVOT.

Conclusions: Long-term outcomes after Ross and Ross-Konno operations in children were satisfactory. However, new-onset aortic regurgitation was progressive and reoperation was needed in some children. Age, aortic annulus diameter, and Ao/PA ratio may be able to predict of long-term outcomes after Ross and Ross-Konno operations.
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http://dx.doi.org/10.1007/s11748-018-1034-7DOI Listing
May 2019

Two Cases of Aortic Root Replacement After Fontan Completion.

World J Pediatr Congenit Heart Surg 2019 07 3;10(4):505-507. Epub 2018 Apr 3.

1 Department of Cardiovascular Surgery, The Heart Institute, Tokyo Women's Medical University, Tokyo, Japan.

Aortic root dilatation is a well-known complication in patients with congenital aortic valve malformation, tetralogy of Fallot, or a double outlet right ventricle. We report two rare patients who underwent composite graft replacement of the aortic root with a mechanical valve, the so-called Bentall-type operation, after Fontan completion. The pathological examination on the resected aortic wall revealed mucoid degeneration in tunica media and elastic fiber fragmentation. Our report emphasizes the need for close observation of these patients over a long-term period.
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http://dx.doi.org/10.1177/2150135118755984DOI Listing
July 2019

A Patient with Advanced Gastric Cancer Who Achieved a Long-Term Prognosis by Early Diagnosis of Sister Mary Joseph's Nodule.

Case Rep Oncol 2018 Jan-Apr;11(1):11-16. Epub 2018 Jan 4.

aDivision of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

The patient was a 66-year-old woman. An induration of approximately 15 mm in size that accompanied redness was palpable in the umbilical fossa. She did not respond to 1-month antibiotic treatment provided by the previous physician. For this reason, a biopsy of the site was performed with the possibility of neoplastic disease in mind, resulting in the detection of adenocarcinoma. Subsequent detailed whole-body examination revealed advanced gastric cancer and peritoneal dissemination, and the induration in the umbilical fossa was diagnosed as a direct infiltration from the peritoneal dissemination. Metastasis or infiltration of malignant tumor to the umbilicus is called Sister Mary Joseph's nodule (SMJN), and considered as a sign of poor prognosis. However, this case was successfully treated and achieved a long-term prognosis by the early diagnosis of SMJN. In routine clinical practice, it is considered necessary to examine patients carefully, as not to overlook SMJN.
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http://dx.doi.org/10.1159/000484976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836228PMC
January 2018

A Case of Lung Adenocarcinoma with Marked Improvement of Pulmonary Lymphangitic Carcinomatosis by Adding Bevacizumab to Cisplatin and Pemetrexed.

Case Rep Oncol 2017 Sep-Dec;10(3):1065-1069. Epub 2017 Nov 27.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

A 40-year-old man with a diagnosis of lung adenocarcinoma (cT4N3M1c, stage IVB) experienced worsening of lymphangitic carcinomatosis in the right lung and right pleural effusion after receiving 1 cycle of first-line chemotherapy consisting of cisplatin and pemetrexed. Bevacizumab was thus added from the second cycle of the cisplatin-pemetrexed regimen, leading to a marked improvement in pulmonary lymphangitic carcinomatosis and a decrease in pleural effusion. Subsequently, maintenance therapy consisting of pemetrexed and bevacizumab was continued, successfully leading to long-term progression-free survival. Generally, pulmonary lymphangitic carcinomatosis shows poor prognosis because of poor response to chemotherapy. However, recent studies have been elucidating the role of the vascular endothelial growth factor A (VEGF-A)/VEGF receptor-2 pathway in pulmonary lymphangitic carcinomatosis. Therefore, bevacizumab is expected to be beneficial in the treatment of this pathological condition.
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http://dx.doi.org/10.1159/000484662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836232PMC
November 2017

Long-term outcomes of total correction for isolated total anomalous pulmonary venous connection: lessons from 50-years' experience.

Interact Cardiovasc Thorac Surg 2018 07;27(1):20-26

Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.

Objectives: Isolated total anomalous pulmonary venous connection (TAPVC) is a relatively rare congenital cardiac defect, while pulmonary venous obstruction (PVO) is associated with poor prognosis. We reviewed the long-term outcome of total correction for isolated TAPVC at our institute and analysed the risk factors for mortality and morbidity.

Methods: A total of 290 isolated TAPVC patients evaluated between 1965 and 2016 were divided into 2 groups: Group Early (n = 151) underwent surgery before 1989; Group Late (n = 139) underwent surgery after 1990. The mean age at operation was 10.4 ± 30.2 months (range 0 day to 23 years), and the mean body weight was 5.5 ± 6.0 kg (range 1.6-48 kg). Group Late included more patients with the infracardiac type of TAPVC and preferably used the posterior approach.

Results: There were 53 hospital deaths and 16 late deaths. Postoperative PVO was recognized in 28 patients. The mean follow-up time was 18.2 ± 9.7 years (range 2 months to 42.4 years). The actuarial survival rate was improved to 87.8% at 20 years in Group Late. Multivariable analysis revealed that death rate was significantly increased in patients of Group Early, with a body weight <2 kg and with postoperative PVO (P < 0.0001, P = 0.0041, P = 0.0003, respectively). Reoperations were performed 27 times in 22 patients (PVO repair, 11; staged repair, 4 and others, 12). PVO repair was performed at a mean of 2.5 ± 1.6 months later. The actuarial freedom from reoperation rates were 88.8% and 83.2% at 20 and 30 years, respectively. Multivariable analysis revealed that the risk of reoperation was associated with mixed-type TAPVC and postoperative PVO (P = 0.0064 and P < 0.0001, respectively).

Conclusions: Long-term surgical outcomes of isolated TAPVC have improved over the past 25 years. Postoperative PVO, the mixed-type TAPVC and a body weight <2 kg might be the important factors contributing to mortality and morbidity.
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http://dx.doi.org/10.1093/icvts/ivy034DOI Listing
July 2018

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy.

Case Rep Oncol 2017 Sep-Dec;10(3):1131-1137. Epub 2017 Dec 20.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB). Based on these findings, he was diagnosed as suffering from paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Thereafter, his symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy for lung adenocarcinoma. Currently, RS3PE syndrome can be classified as a vascular endothelial growth factor (VEGF)-associated disorder. Given that his symptoms improved by chemotherapy, the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF. Therefore, the present case suggested that the symptoms of acute-onset joint pain accompanied by pitting edema in elderly patients should be considered suspicious for a malignant tumor, thereby warranting a detailed full-body examination.
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http://dx.doi.org/10.1159/000484977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803715PMC
December 2017

A Case of Advanced Submandibular Gland Cancer in Which Increased Prostate-Specific Antigen and Multiple Bone Metastases Wrongly Suggested Concurrent Prostate Cancer.

Case Rep Oncol 2017 Sep-Dec;10(3):1127-1130. Epub 2017 Dec 20.

Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

A 73-year-old man, followed for prostatic hyperplasia, developed submandibular gland cancer. Initially, because of the concurrent presence of elevated serum prostate-specific antigen (PSA) and multiple bone metastases, he was clinically determined as having stage IV prostate cancer in addition to stage II submandibular gland cancer, and radical surgery for his submandibular gland cancer was performed first. However, subsequent detailed examinations of the prostate gland showed no prostate cancer, and a diagnosis of advanced submandibular gland cancer with increased PSA and multiple bone metastases was established. Serum PSA is highly specific for prostate diseases and is widely used as a tumor marker of prostate cancer. However, clinicians should be aware that, in patients with non-prostate cancer, the detection of increased PSA and multiple bone metastases does not necessarily indicate the concurrent presence of prostate cancer.
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http://dx.doi.org/10.1159/000484975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803733PMC
December 2017

Twenty-year experience with the Konno operation: Konno incision does not impair LV function.

Gen Thorac Cardiovasc Surg 2018 May 2;66(5):270-275. Epub 2018 Feb 2.

Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo, 162-8666, Japan.

Background: There has been no report observing the LV function of Konno incision. We examined the outcomes of the Konno operations over 20 years.

Methods: We investigated 63 Konno operations with mechanical valves performed from 1984. This study aimed to evaluate the effects of Konno incision including LV function changes and the long-term outcomes of patient survival and reoperation rate (RVOT and LVOT complications).

Results: The postoperative follow-up period was 20.6 ± 6.2 years. Early death occurred in 1 case and late death occurred in 9 cases. The cumulative survival rate was 89.6, 87.5, and 84.5% in the 5th, 10th, and 20th follow-up years. Five patients required reoperation for the aortic valve. The recurrence avoidance rate for LVOT reoperation was 96.6, 94.7, and 92% in the 5th, 10th, and 20th follow-up years of the Konno operation. Konno incision did not show significant decline in postoperative LV ejection fraction. (Pre, 62% vs 20 years later, 58%; P = 0.052.) There were no cases requiring intervention at the event of ventricular arrhythmia, but 13 cases were Complete Right bundle branch block, and 11 cases were Left bundle branch block.

Conclusions: The survival rate associated with Konno operation throughout 20 years was excellent. Konno incision can secure sufficient LV outflow tract and is a safe treatment for complex LVOTO without deteriorating LV ejection fraction.
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http://dx.doi.org/10.1007/s11748-018-0896-zDOI Listing
May 2018

Paraneoplastic IgA Vasculitis in an Adult with Lung Adenocarcinoma.

Intern Med 2018 May 27;57(9):1273-1276. Epub 2017 Dec 27.

Division of Medical Oncology, Teikyo University School of Medicine, Japan.

A 50-year-old man with lung adenocarcinoma (c-T1aN2M1b) experienced reddish purpura mainly on the lower legs after receiving 12 cycles of second-line chemotherapy with docetaxel. There was tumor enlargement on computed tomography performed to assess the therapeutic response, so paraneoplastic IgA vasculitis was considered. IgA vasculitis was diagnosed based on a biopsy of the skin lesion and histology of an upper gastrointestinal hemorrhagic mucosal erosion. As IgA vasculitis can lead to serious gastrointestinal or systemic complications, IgA vasculitis should be considered as a differential diagnosis for rashes in patients with malignancy.
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http://dx.doi.org/10.2169/internalmedicine.9651-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980809PMC
May 2018

Thrombus formation 4 years after percutaneous transcatheter closure of an atrial septal defect.

J Card Surg 2017 Aug 25;32(8):492-493. Epub 2017 Jul 25.

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Tokyo, Japan.

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http://dx.doi.org/10.1111/jocs.13178DOI Listing
August 2017

[Atrial Septal Hematoma after Repair of Ventricular Septal Defect;Report of a Case].

Kyobu Geka 2017 Jul;70(7):529-531

Department of Cardiovascular Surgery, Tokyo Women's Medical University, Tokyo, Japan.

A 3-month-old female with ventricular septal defect underwent definitive repair. In the operation, a venting tube was inserted through the incised patent foramen ovale. The ventricular septal defect was closed using a patch and the incised patent foramen ovale was directly closed. A transesophageal echography showed no abnormal findings in the operating room. On 1st postoperative day, the patient's heart rate and pressure of the superior vena cava increased while blood pressure decreased. A transthoracic echocardiography revealed an atrial septal hematoma. After conservative therapy, the heart rate and pressure of the superior vena cava gradually decreased while blood pressure increased. The atrial septal hematoma disappeared spontaneously. The patient was discharged on 16th postoperative day. The atrial septal hematoma appears to have a good prognosis, but sometimes can be poor resulting and death. Meticulous and constant observation is required to detect an atrial septal hematoma.
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July 2017

Long-Term Outcome of Arterial Switch Operation Conversion After Failed Senning/Mustard Procedure.

Ann Thorac Surg 2016 Nov 2;102(5):1573-1579. Epub 2016 Jun 2.

Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.

Background: We evaluated long-term outcomes of the arterial switch operation (ASO) conversion after a failed Senning/Mustard operation among patients with dextro-transposition of the great arteries.

Methods: Between 1986 and 2006, 9 patients with dextro-transposition of the great arteries underwent ASO conversion at our institute. All patients had systemic right ventricle failure, 6 had supraventricular tachycardia, and 8 had moderate or severe tricuspid valve regurgitation. All patients had New York Heart Association classification II or III. The median age of patients at the ASO conversion operation was 7.4 years (range, 0.6 to 32.4 years). Pulmonary artery banding for left ventricle training was performed in 8 of the 9 patients before conversion.

Results: There was 1 early death from low-output syndrome at 5 days postoperatively and 1 late sudden death at 5 months. Median follow-up time was 23.1 years (range, 0.08 to 28.0 years). The actuarial survival rate was 76.1% at 20 years. Long-term survivors revealed good New York Heart Association classification (class I, 6 patients; class II, 1 patient), with less than mild tricuspid regurgitation and brain natriuretic peptide levels of 40.6 ± 16.2 pg/mL. Cardiac catheterization revealed significant improvements of right ventricle end-diastolic volume (decreased from 243.2% to 117.7% of normal), and right ventricle ejection fraction (increased from 0.42 to 0.572; p < 0.05). Three patients underwent new pacemaker implantation for sick sinus syndrome, and moderate neoaortic valve regurgitation developed in 1 patient.

Conclusions: Excellent long-term outcomes can be achieved after ASO conversion; however, careful observation for new-onset sick sinus syndrome and aortic regurgitation is mandatory.
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http://dx.doi.org/10.1016/j.athoracsur.2016.03.114DOI Listing
November 2016

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

J Med Ultrason (2001) 2017 Jan 1;44(1):133-139. Epub 2016 Oct 1.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan.

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.
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http://dx.doi.org/10.1007/s10396-016-0746-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222898PMC
January 2017

Fontan circulation over 30 years. What should we learn from those patients?

Asian Cardiovasc Thorac Ann 2016 Oct 24;24(8):765-771. Epub 2016 Aug 24.

Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.

Background: This study aimed to evaluate Fontan circulation which was observed over 30 years.

Methods: Forty patients who underwent a Fontan operation between 1974 and 1986 and survived (group S, n = 20) or died in the late period (group LD, n = 20) were evaluated. The median age at operation was 10 years (range 2-32 years). The diagnoses were tricuspid atresia in 21, single ventricle in 9, and others in 10. The Fontan procedure was a right atrium-pulmonary artery graft in 2, atriopulmonary connection in 28, and right atrium-right ventricle anastomosis in 10 (Björk in 4, graft in 6).

Results: Causes of late death were congestive heart failure in 6, sudden death in 4, arrhythmia in 4, and others in 6. Sixteen patients underwent reoperation 23.3 ± 6.5 years after Fontan. Cardiac catheterization was performed at 1 month and 12 years. There were no significant differences in central venous pressure, ventricular ejection fraction, or pulmonary vascular resistance between the two groups. However, changes in ventricular end-diastolic volume suggested volume and pressure overload in group LD. In group S, the latest chest radiographs showed cardiothoracic ratio 51.3% ± 7.6%, oxygen saturation 94% ± 2%, brain natriuretic peptide 153 ± 111 pg ċ mL, and Holter monitoring revealed sinus rhythm in 10 patients. New York Heart Association class was I in 12 patients, II in 6, and III in 2.

Conclusions: For long-term Fontan survival, timely total cavopulmonary connection conversion and medication to decrease ventricular volume and pressure load might be important.
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http://dx.doi.org/10.1177/0218492316667771DOI Listing
October 2016

Successful staged Fontan completion for a tricuspid atresia patient with left ventricular non-compaction.

Interact Cardiovasc Thorac Surg 2016 Mar 20;22(3):387-9. Epub 2015 Dec 20.

Department of Cardiovascular Surgery, Nagano Children's Hospital, Azumino, Japan.

We report a case of Fontan completion for a tricuspid atresia (TA) patient with left ventricular non-compaction (LVNC). The patient was diagnosed with TA (Ia) with LVNC by fetal echocardiography. Because the unfavourable prognosis of LVNC was anticipated, Imidapril as well as Carvedilol were administered to improve cardiac function, from the early stages of infancy. Staged Fontan completion with fenestration was successfully achieved with improvement of LV function.
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http://dx.doi.org/10.1093/icvts/ivv356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986567PMC
March 2016

Current status of brain protection during surgery for congenital cardiac defect.

Gen Thorac Cardiovasc Surg 2016 Feb 30;64(2):72-81. Epub 2015 Nov 30.

Division of Pediatric Cardiovascular Surgery, Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

The long-term neurodevelopmental outcome has been a great concern for cardiac surgeons although it is still unclear. There are some risks regarding the neurological and neuropsychological deficits before, during and after cardiovascular surgery. Current status of brain protection during congenital heart surgery could be reported. The incidence of neurologic outcome and the appropriate CPB strategy for brain protection are stated, and the latest data of neurodevelopmental outcome after pediatric cardiac surgery are clarified.
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http://dx.doi.org/10.1007/s11748-015-0606-zDOI Listing
February 2016

Feasibility study of docetaxel plus bevacizumab as first line therapy for elderly patients with advanced non-small-cell lung cancer: Thoracic Oncology Research Group (TORG) 1014.

BMC Cancer 2015 Oct 19;15:740. Epub 2015 Oct 19.

Yokohama Municipal Citizen's Hospital, 56 Kazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan.

Background: Docetaxel monotherapy is one of the standard treatments for non-small-cell lung cancer in elderly patients. The addition of bevacizumab to docetaxel seems promising; however, the feasibility of this combination has not been investigated in such patients.

Methods: Patients with advanced non-squamous non-small-cell lung cancer aged 70 years or older who had not previously received cytotoxic chemotherapy were enrolled. Patients in the Level 0 cohort received docetaxel 60 mg/m(2) and bevacizumab 15 mg/kg, whereas those in the Level-1 cohort received docetaxel 50 mg/m(2) and bevacizumab 15 mg/kg. Chemotherapy was repeated 3 weekly for six cycles. The primary endpoint was toxicity and the secondary endpoints were response rate, progression-free survival, overall survival, and proportion of patients who underwent three or more cycles of chemotherapy.

Results: Twenty-one patients were enrolled from December 2010 to September 2012 at six institutes. Of the nine patients enrolled in Level 0, two experienced dose-limiting toxicity (febrile neutropenia and prolonged Grade 4 neutropenia in one patient, and Grade 3 infection in another patient) during the first cycle. Enrollment to the Level 0 cohort was terminated because two patients developed Grade 4 sepsis during later cycles. The remaining 12 patients were enrolled in the Level-1 cohort, in which two dose-limiting toxicities (prolonged Grade 4 neutropenia and Grade 3 increased aminotransferase level) were observed. No patient in the Level-1 cohort experienced Grade 4 nonhematologic toxicity. Grade 4 neutropenia occurred in 89 % of Level 0 patients and 50 % of Level-1 patients. The proportion of patients who experienced Grade 3/4 infection, febrile neutropenia or sepsis was 44 % in the Level 0 cohort, and 8 % in the Level-1 cohort. The overall response rate to chemotherapy and progression-free survival were 29 % (95 % CI, 11-52 %) and 5.9 months (95 % CI, 3.6-9.1 months), respectively. Efficacy outcomes did not differ significantly between the cohorts.

Conclusions: Toxicities were tolerable in level-1 cohort. The recommended dose of combination chemotherapy with docetaxel and bevacizumab for elderly patients was determined as 50 mg/m(2) of docetaxel and 15 mg/kg of bevacizumab and toxicities were tolerable. Further studies are warranted.

Trial Registration: UMIN Clinical Trial Registry; UMIN000004240 .
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http://dx.doi.org/10.1186/s12885-015-1756-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612532PMC
October 2015

[Impacts of bilateral pulmonary artery banding on the surgical and long-term outcomes in hypoplastic left heart syndrome( HLHS) and its variants].

Kyobu Geka 2014 Apr;67(4):278-85

Department of Cardiovascular Surgery, Nagano Children's Hospital, Azumino, Japan.

Although Norwood-type operation is a fundamental procedure for hypoplastic left heart syndrome and its variants, the surgical risk is still high even in the high volume center. Bilateral pulmonary artery (PA) banding( BPAB) is an alternative procedure to avoid the risk in the neonatal period. We clarified the impacts of BPAB on the surgical and long-term outcomes in HLHS and its variants. Consecutive 85 patients( classical HLHS:52, variant:33) who underwent surgical intervention between July, 1993 and December, 2012 were evaluated. Fetal diagnosis was done in 37 patients (44%). Forty-two patients underwent primary Norwood operation[ Gp N, Blalock-Taussig( BT):29, right-ventricle( RV)-PA conduit:13] and the remaining 43 patients underwent BPAB followed by Norwood operation. Among them, 4 patients did not reach Norwood [9%, atrioventricular valve regurgitation (AVVR):1, infection:1, preoperative shock:2). The survived 39 patients were divided into 2 groups;Gp BN (BPAB → Norwood+BT/RV-PA conduit, n=22), Gp BG [BPAB → Norwood+bidirectional Glenn procedure(BDG), n=17]. BPAB for HLHS and its variants is useful in terms of lower mortality. The 2nd stage palliation is so important that modified Norwood procedure with BT shunt or RV-PA conduit contribute to the lower morbidity including neurological outcome. Norwood+BDG strategy might be beneficial for the high risk patients such as with poor cardiac function or low body weight.
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April 2014

Spontaneous dissection of the arterial duct during continuous infusion of prostaglandin E1 in a neonate with aortic arch interruption.

J Echocardiogr 2013 Dec 31;11(4):155-7. Epub 2013 Jul 31.

Department of Cardiothoracic Surgery, Nagano Children's Hospital, Azumino, Japan.

We report a 3-day-old boy with double outlet of the right ventricle and interruption of the aortic arch who developed spontaneous dissection of the arterial duct (DA) despite use of continuous infusion of lipo-prostaglandin E1 (PGE1). Transthoracic echocardiography demonstrated the spontaneous dissecting aneurysm of DA, which was confirmed by histology at the modified Norwood procedure done at age of 18 days. This is the first report of spontaneous dissection of DA in a neonate receiving PGE1, suggesting a new closing mechanism of DA.
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http://dx.doi.org/10.1007/s12574-013-0188-7DOI Listing
December 2013