Safety analysis of ZiagenR (abacavir sulfate) in postmarketing surveillance in Japan

Purpose: Abacavir is a nucleoside reverse transcriptase inhibitor indicated for human immunodeficiency virus (HIV) infection. In Japan, ZiagenR (300-mg abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen, a mandatory postmarketing surveillance was conducted between September 1999 and September 2009. Methods: A joint survey [HIV-related Drug Surveys (HRD)] has been conducted involving manufacturers of drugs for HIV treatment in Japan. Safety data from total 643 cases (1345.7person-years) registered to the HRD surveys and received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse event of which association with abacavir could not be "ruled out." Results: It was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs were "hyperlipidemia," "nausea," "increased γ-glutamyltransferase level," "increased blood triglycerides," "abnormal hepatic function," and so on. Serious adverse events were reported in 65 subjects; however, none of the three fatal cases were clearly associated with Ziagen use. The survey-defined hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although some studies had indicated of the association between abacavir and myocardial infarction, no ischemic heart diseases were reported in the present survey. Two of the three pregnant cases delivered normal neonates (one induced abortion). Conclusions: During the mandatory postmarketing survey of Ziagen, there were no cases of ischemic heart diseases, and the incidence of hypersensitivity was considerably low. These indicated that abacavir can be safely used in Japanese HIV+ population. However, the safety profile of Ziagen should be continued to be monitored through pharmacovigilance

Safety analysis of EpzicomR (lamivudine/abacavir sulfate) in post-marketing surveillance in Japan

Purpose: To obtain safety and effectiveness data on a combined anti-HIV drug, Epzicom (abacavir 600mg/lamivudine 300mg), a post-marketing surveillance on Epzicom that was required by the Japanese regulatory authority was conducted between January 2005 and December 2010. Methods: A joint survey (HIV-related drug [HRD] survey) has been conducted involving manufacturers of drugs for treatment of HIV infection in Japan. Safety and effectiveness data from total 624 cases (1107.3person-years) registered to the HRD surveys and received Epzicom were obtained. Adverse drug reactions (ADRs) were defined as adverse events (AE) of which association with Epzicom could not be \u27ruled out\u27. Results: It was found that the incidence of ADR was 32.4% (202/624 cases) on the case basis. In addition, the frequently reported ADR included hyperlipidaemia (59 cases), hypertriglyceridaemia (21 cases), blood bilirubin increased (19 cases), gamma-glutamyltransferase increase (14 cases), blood triglyceride increase (14 cases) and rash (14 cases). Serious AEs were seen in 19 patients (30 events), including one death (no evident association with Epzicom). There were four cases (0.6%) of survey-defined \u27hypersensitivity\u27, and the incidence was 0.9% (4/445) among abacavir naive patients; none of which was reported as serious. No case of myocardial infarction was reported. One pregnant case who delivered a normal baby by caesarean section was reported to have experienced aggravation of anaemia and nausea. Conclusions: The post-marketing surveillance indicated that the incidence of both ischaemic heart disease and hypersensitivity associated with Epzicom was considerably low, suggesting that this drug can be safely used in the Japanese population

A case of primary breast cancer with chronic phase chronic myelogenous leukemia

A female patient in her ４０s was admitted because of right breast swelling and pain. She had been taking Nilotinib（a molecular targeted drug）for ４months as treatment for chronic-phase chronic myelogenous leukemia. She was diagnosed with advanced breast cancer by cytology and histological examinations. She received neoadjuvant chemotherapy and had obtained a partial response. She then underwent a nipple-sparing mastectomy and axillary lymph node dissection. Therefore, in this patient, breast cancer and chronic myelogenous leukemia coexisted. Chemotherapy for breast cancer and a molecular targeted drug for chronic-phase chronic myelogenous leukemia were administered concurrently

Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer.

OBJECTIVES: The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. METHODS: Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. RESULTS: Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. CONCLUSIONS: These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment

術後肺ヘルニアに対し，緊急修復手術を施行した１症例

A male patient, in his ５０s, was admitted owing to rear neck pain and stomachache. He was diagnosed Type A acute aortic dissection and underwent a total arch aortic replacement operation. Five days later, he developed dyspnea after he coughed. He was diagnosed left lung hernia, mediastinal emphysema and pneumothorax by a chest CT scan. We repaired pulmonaly fistula and lung hernia using an ePTFE patch

甲状腺癌リンパ節転移との鑑別が困難であった頸部神経鞘腫の１例

A female patient in her 60s visited her previous doctor because of a right cervical mass that exist for 7 years and gradually increased in size. As she was suspected of cervical lymph node metastasis of thyroid cancer, she was referred to our hospital. At the initial visit, a 5-cm right cervical mass and enlargement of the right lobe of the thyroid gland were observed. Fine needle aspiration cytology was performed on both, but no malignant findings were observed. To confirm the diagnosis and improve the patient’s appearance, a right lobectomy of the thyroid gland and resection of the right cervical mass were performed. A rapid intraoperative histological examination of the cervical mass revealed a schwannoma. The right thyroid tumor was diagnosed as follicular adenoma. Her postoperative course was good, and after several years of follow-up, patient consultation was terminated. Neurolemmoma is a benign tumor arising from Schwann cells in the nerve sheath, and it occurs frequently throughout the head and neck region, with 25%-45% of cases occurring in this region. Cervical schwannomas are characterized by irritation of the vagus nerve, brachial plexus, and sympathetic nerves. However, many patients present with only a painless neck mass, as in this case. Although the mass can be diagnosed by puncture aspiration cytology in some cases, sufficient specimens are often unavailable, and the diagnosis is made preoperatively in about half of all cases. Differential diagnoses of an anterior cervical mass include malignant lymphoma, cervical lymph node metastases of malignant tumors, submandibular gland tumors, and tuberculous lymph node metastases. In this patient, we also considered lymph node metastasis of thyroid cancer. However, a histological examination did not detect malignancy in either the thyroid gland or neck mass, and we considered that the thyroid follicular adenoma and the cervical schwannoma occurred independently. We report our experience of cervical schwannoma combined with thyroid tumor which was suspected of lymph node metastasis of thyroid cancer

Two cases of pulmonary dirofilariasis

Pulmonary dirofilariasis is almost always asymptomatic. An abnormal nodule was accidentally discovered by a chest x-ray during a medical checkup and detailed examination for other diseases was performed. Case １. A female patient, in her ７０s, was admitted owing to flu-like symptoms and bloody sputum. A chest computed tomography（CT）scan revealed a nodular shadow with １０‐mm ground glass opacity in the right lower lobe. Case２. A female patient, in her ６０s, was admitted due to an abnormal shadow on a chest xray in the left lung during a regular medical checkup. A chest CT scan revealed a nodular shadow with １３‐mm ground glass opacity in the left upper lobe. Lung cancer was suspected in both cases. Thoracoscopy and partial lung resection were performed to confirm the diagnosis. The specimen consisted of granulation tissue and no malignancy was found at operation. Final pathological diagnosis revealed pulmonary dirofilariasis. Pulmonary dirofilariasis can be definitively diagnosed by detecting a worm body. We believe partial lung resection during video-assisted thoracic surgery is a minimally invasive and an effective treatment for this disease

キョウクウキョウカ ニ セツジョ シタ ジュウカクナイ イショセイ フクコウジョウセン センシュ

A woman in her ６０s who was diagnosed as having hypercalcemia and hyperparathyroidism was referred to our hospital. Serum calcium and intact parathyroid hormone levels were１１．４mg/ ml and １０７ pg/ml, respectively. Chest computed tomography revealed an enhanced mass measuring approximately１．５cm located in the anterior mediastinum. ９９mTc-Methoxy-isobutylisonitrile scintigraphy demonstrated an anterior mediastinal mass. These findings suggested an ectopic parathyroid tumor located in the mediastinum. The patient underwent resection of the parathyroid tumor with video-assisted thoracic surgery（VATS）. The operation time was １１４ min. The postoperative day１（POD１）calcium level rapidly decreased to８．３mg/ml. The patient was discharged on POD５, and there have been no signs of recurrence １ year after the surgery. Parathyroidectomy by VATS for ectopic mediastinal parathyroid tumors is advantageous because it is less invasive and more cosmetic. VATS may be used as a standard approach for ectopic mediastinal parathyroid tumors. We report the surgical treatment of a case of ectopic mediastinal parathyroid adenoma using video-assisted thoracoscope

AYA-generation lung cancer in a patient presenting with spontaneous pneumothorax : A case report

Background : Surgery for young patients（i.e., <２０ years of age）with early-stage lung cancer is extremely rare. To the best of our knowledge, only a few cases of lung cancer initially presented with spontaneous pneumothorax. Here, we report a case of AYA（adolescent and young adult）-generation lung cancer in a patient who presented with spontaneous pneumothorax. Case : An １８-year-old male was admitted to our hospital for new-onset left pneumothorax. Chest computed tomography incidentally revealed a pure ground-glass nodule（pGGN）in the left lower lobe（S８）with a bulla near the nodule. While chest tube drainage improved his condition, pneumothorax recurred two weeks later, prompting surgical for video-assisted partial resection of the left lung. Intraoperative findings showed that the bulla and nodule were distant. Histopathologic analysis was consistent with a diagnosis of adenocarcinoma in situ with a bleb. Conclusion : This study highlights the importance of considering the possibility of lung cancer in patients with irregular chest shadows, even those less than２０years of age. Computed tomography plays an important role in the diagnosis of lung cancer in patients with spontaneous pneumothorax