Shigetoshi Ichii

Evaluation of ultrasound-guided fine-needle aspiration biopsy for thyroid nodules

BACKGROUND We retrospectively studied whether ultrasound-guided fine-needle aspiration biopsy (US-FNAB) showed improved sensitivity in patients with palpable thyroid nodules. METHODS A total of 70 patients (72 lesions) with thyroid nodules underwent US-FNAB and 94 patients (94 lesions) underwent FNAB guided by manual palpation (standard FNAB). The diagnoses obtained by US-FNAB were compared with the surgical findings. RESULTS The sensitivity of US-FNAB for palpable thyroid nodules was 62% the specificity was 74% the accuracy was 68% the positive predictive value was 100%, the negative predictive value was 70% and the inadequate biopsy rate was 17%. In contrast, the sensitivity of standard FNAB was 45%, the specificity was 51%, the accuracy was 48% the positive predictive value was 96, the negative predictive value was 55, and the inadequate biopsy rate was 30%. The accuracy of US-FNAB was significantly higher than that of standard FNAB. For tumors < or = 2 cm in diameter, the sensitivity and accuracy of US-FNAB were both significantly higher than those of standard FNAB. CONCLUSION These findings suggest that US-FNAB can improve the preoperative diagnosis of thyroid cancer, especially in patients with tumors < or = 2 cm in diameter.

Diagnostic value of ultrasound-guided fine-needle aspiration biopsy, core-needle biopsy, and evaluation of combined use in the diagnosis of breast lesions

BACKGROUND To investigate whether ultrasound-guided core-needle biopsy (US-CNB) has more diagnostic value for breast tumors than ultrasound-guided fine-needle aspiration biopsy (US-FNAB) and to evaluate their combined use in patients with breast tumors. STUDY DESIGN US-FNAB was carried out in 233 patients with breast tumors (254 lesions); both US-FNAB and US-CNB (combined biopsy) were performed in 81 of these patients (82 lesions). The diagnosis obtained by US-FNAB and US-CNB was compared with the surgical findings and the diagnostic value of US-CNB and combined biopsy were retrospectively evaluated. RESULTS The sensitivity of US-FNAB was 86.9%, the specificity was 78.6%, and the accuracy was 84%. In contrast, the sensitivity of US-CNB was 86.2%, the specificity was 95.8%, and the accuracy was 89%. The specificity of US-CNB was significantly higher than that of US-FNAB and the inadequate biopsy rate of US-CNB was significantly lower than that of US-FNAB. For combined biopsy, the sensitivity, specificity, and accuracy were all 100%. The sensitivity, specificity, and accuracy of combined biopsy were significantly higher than those of US-FNAB. CONCLUSIONS These findings suggest that US-CNB is more useful than US-FNAB, and that a combination of US-CNB and US-FNAB can markedly improve the preoperative diagnosis of breast cancer.

Ultrasound-guided fine-needle aspiration biopsy for breast tumors: needle guide versus freehand technique.

Background We retrospectively studied whether a needle guide is necessary when performing ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in patients with breast tumors. Methods A total of 47 patients (50 lesions) with breast tumors underwent US-FNAB with a needle guide and 127 patients (143 lesions) underwent the procedure without a needle guide (freehand biopsy). The diagnoses obtained by US-FNAB were compared with the surgical findings. Results The sensitivity of freehand biopsy for tumors <3 cm in diameter was significantly higher than that of the needle guide technique. Conclusions We recommend performing US-FNAB without a needle guide (freehand biopsy) in order to maximize the correct preoperative diagnosis rate, especially in patients with tumors <3 cm in diameter.

Accessory breast cancer: a case report and review of the Japanese literature.

The case of a 31-year-old woman with accessory breast cancer in the left axilla is described. She had noticed a swelling in the left axilla during her three pregnancies. The preoperative diagnosis of accessory breast cancer was made on the basis of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) and clinical history. She was treated by wide local resection and regional lymph node dissection. Although cancer originating from accessory breast tissue has been reported very rarely, knowledge of this disorder may facilitate the correct diagnosis of axillary tumors. US-FNAB is a useful and simple technique for the tissue diagnosis of axillary tumors.

Thyroid cancer in uremic patients.

Background The combination of thyroid cancer and secondary uremic hyperparathyroidism has thus far been reported in only 25 cases. Methods Here we report our experience of 19 patients with secondary hyperparathyroidism who underwent parathyroidectomy. Results Thyroid nodules were present in five patients (26.3%), including one with a benign nodule and four with papillary thyroid cancer (21.1%). Conclusion Our experience suggests that, in order to make a correct diagnosis, clinicians should consider the possibility of thyroid cancer in uremic patients with secondary hyperparathyroidism.

A new alternative splice variant of the mouse fas antigen with a deletion in the N-terminal portion of the extracellular domain

The Fas antigen (Fas/APO-1/CD95) has been shown to induce apoptosis when bound to a monoclonal anti-Fas antibody or Fas ligands. Recently, a new soluble human Fas isoform which lacks the transmembrane domain due to alternative splicing has been isolated; however, no mouse Fas isoforms have been reported so far. Analysis of Fas transcripts by RT-PCR detected no Fas transcripts corresponding to the human soluble Fas isoform in mouse thymus, spleen and liver. However, we detected a new isoform with a 117-bp deletion in the second exon in various mouse tissues and cell lines. This isoform, termed truncated Fas (T-Fas), can be generated by alternative splicing and lacks the N-terminal portion of the extracellular domain just after the signal sequence. Since the deletion involves the first cysteine-rich motif believed to be necessary for binding to the Fas ligand, the T-Fas protein may lack the ability to induce apoptosis. The expression of T-Fas relative to that of the normal Fas varies considerably among mouse tissues and cell lines, suggesting preferential transcription of the T-Fas isoform in certain cell types.

Abstract P1-13-07: Chemotherapy, but not body mass index has impact on joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: A prospective multicenter cohort study of patient-reported outcomes

Background: Endocrine treatment-related adverse events have a strong impact on patients’ quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side-effect of aromatase inhibitors, evaluation of associated risk factors may well be important. Among high body mass index (BMI) and chemotherapy have been associated with the development of joint symptoms in patients enrolled in ATAC trials. To determine the impact of these factors on treatment-emergent joint symptoms in Japanese breast cancer treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs). Patients and Methods: Postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled in this prospective cohort study (SAVS-JP, UMIN000002455). A total of 416 patients were recruited from 30 centers for PRO assessment at their after-care appointments between August 2009 and April 2012. Patients completed the self-report questionnaire at baseline, 3, 6, 9 and 12 months. Symptoms were assessed as four categories (none, Grade 1: somewhat, Grade 2: quite a bit, Grade 3: very much). Pre-existing symptoms were only included if they worsened from baseline. The endpoint of this study was the frequencies of treatment-related joint symptoms, which included reports of arthralgia, decrease of joint motion, and joint stiffness. Results: We obtained PROs from 391 (94.0%) of the 416 patients at baseline and at one or more points during treatment, so that 391 patients were analysed. Joint symptoms at baseline were reported by 134 (34.3%) patients and new or worsening symptoms were experienced by 258 (66.0%) patients. The symptoms were graded as: grade 1, 53.1%; grade 2, 37.6%; grade 3, 9.3%. Mean time to onset of joint symptoms was 5.4 months, and nearly 80% had developed symptoms by 6 months. Twelve patents discontinued treatment during the first year and two patients withdrew due to joint symptoms. Patients with joint symptoms were significantly younger (age: 63.1; standard deviation: 7.9) than those without symptoms (age: 65.8: 8.4; p = 0.0045). We categorized BMI into three groups (low: Discussion: The incidence of anastrozole-associated joint symptoms was more than 60%, with most women having developed symptoms by 6 months. The PROs may disclose higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials. We found that younger age and adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These data should prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors for postmenopausal Japanese women. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-07.

Long-term role of nitric oxide in the enteric nervous system of the transplanted rat intestine

Abstract We investigated the longterm changes of the nitric oxide (NO)‐related neural component after syngeneic total small bowel transplantation in rats. In the present study, the NO‐related neural component was examined using the electrophysiological and NADPH‐diaphorase histochemical technique. The rats were divided into four groups: an untreated young adult control group, an untreated 2‐year‐old control group, a group killed 1 month after transplantation, and a group killed 2 years after transplantation. A superfusion apparatus was used to evaluate the response of jejunal strips to electrical transmural stimulation. In the presence of adrenergic and cholinergic blockade, the inhibitory effect of L‐NG‐ nitro arginine (L‐NNA; a nitric oxide synthesis inhibitor) on nonadrenergic, noncholinergic (NANC) relaxation was expressed as a L‐NNA‐sensitive component. The L‐NNA‐sensitive component accounted for 41.6 ± 4.6% (mean = SE), 43.1 ± 3.5%, 54.6 ± 4.1 %, and 55.8 ± 3.5 % in the young control group, 2‐year control group, 1‐month transplant group, and 2‐year transplant group, respectively, being significantly higher in the transplant groups (p < 0.05). The actual strength of the L‐NNA‐sensitive component was 0.24 ± 0.03 (mean ± SE), 0.26 ± 0.02, 0.44 ± 0.04, and 0.46 ± 0.04 mg of tension per mg of wet weight, respectively, also being significantly higher in the transplant groups (p < 0.001). In addition, the percentage of NADPH‐diaphorase‐positive fibers was 24.1 ± 1.1% (mean ± SE), 25.5 ± 1.4%, 31.0 ± 1.6%, and 30.9 ± 2.0%, respectively, being significantly higher in the transplant groups (p < 0.05). These results suggest that NO neurons in the intrinsic jejunal nervous system have an adaptive role in maintaining intestinal graft motility.

Abstract P1-12-04: Factors influencing on discontinuation of adjuvant anastrozole in postmenopausal Japanese breast cancer patients: Results from a prospective multicenter cohort study of patient-reported outcomes

Background: Adjuvant five-year treatment with aromatase inhibitors is standard for postmenopausal women with estrogen receptor positive breast cancer. However, aromatase inhibitor-related adverse events including joint symptoms and vasomotor symptoms have a strong impact on patients9 quality of life and sometimes result in treatment discontinuation. The aim of this study is to determine risk factors for discontinuation of endocrine therapy in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole in a prospective cohort study based on patient-reported outcomes (PROs). Patients and Methods: A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers in this prospective cohort study (SAVS-JP, UMIN000002455). PROs assessment was obtained at baseline, 3, 6, 9 and 12 months which included joint and vasomotor symptoms. Long-term adherence of anastrozole was obtained form 364 out of 391 patients (median follow-up: 44 months, range: 5-105months). We analyzed the relationship of discontinuation of anastrozole with joint and vasomotor symptoms induced by treatment, and patients’ characteristics. Results: Among 364 patients, 64 (17.6%) discontinued, 297 (81.6%) are ongoing and 3 (0.8%) have completed five-year anastrozole treatment. The reasons for discontinuation were recurrence: 20 (31.3%), secondary malignancies: 5 (7.8%), death from non-breast cancer: 1 (1.6%) and adverse events: 38 (59.4%). These 38 patients who stopped treatment caused by adverse events were compared with other 323 patients. Joint and vasomotor symptoms were categorized into grade 0 (no symptom or no change from baseline), grade 1+2 (mild+moderate) and grade 3 (severe). Grades of joint symptoms were significantly associated with discontinuation of anastrozole (Grade 0: 9.7%, grade 1+2: 7.8%, grade 3: 25.0%, p=0.02). Patients with longer time after menopause (16 years or longer) were significantly higher frequency of discontinuation as compared with shorter time after menopause (0-15years) (14.9% vs 8.0%, p=0.04). Univariate analysis revealed that grade 3 joint symptoms (odds ratio: 3.67, 95% confidence interval: 1.34-10.04, p=0.01) and longer time after menopause (OR: 2.01, 95%CI: 1.01-4.00, p=0.04) were significant risk factors for discontinuation. By multivariate analysis, both grade 3 joint symptoms and long time after menopause were independently associated with discontinuation. Conclusion: In the present study, we have identified that grade 3 joint symptoms and longer time after menopause were risk factors for discontinuation of adjuvant anastrozole. These data might give us useful information for counseling in patients with adjuvant aromatase inhibitors for postmenopausal Japanese women. Citation Format: Chiyomi Egawa, Shintaro Takao, Kazuhiko Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Yasuo Miyoshi. Factors influencing on discontinuation of adjuvant anastrozole in postmenopausal Japanese breast cancer patients: Results from a prospective multicenter cohort study of patient-reported outcomes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-04.