Keiichi Nakano

An Observation Trial Without Surgical Treatment in Patients with Papillary Microcarcinoma of the Thyroid

The recent prevalence of ultrasound-guided fine-needle aspiration biopsy has resulted in a marked increase in the number of patients with papillary microcarcinoma (maximum diameter, </= 10 mm) of the thyroid detected by this sophisticated tool. On the other hand, it is debatable whether patients with papillary microcarcinoma should always undergo surgery after diagnosis, because a high incidence of occult papillary carcinoma has been observed in autopsy studies. Thus, we proposed observation without surgical therapy as a treatment option in 732 patients diagnosed with papillary microcarcinoma by the above technique from 1993 to 2001. One hundred sixty-two patients chose observation and were classified as the observation group. During the follow-up period for patients in the observation group, more than 70% of tumors either did not change or decreased in size compared to their initial size at diagnosis. They enlarged by more than 10 mm in 10.2%, and lymph node metastasis in the lateral compartments appeared in only 1.2% of patients during follow-up. On the other hand, 570 patients chose surgical treatment at diagnosis and 56 patients in the observation group who underwent surgery after a period of follow-up were classified as the surgical treatment group. Of these 626 patients, lymph node dissection was performed in 594 patients, and metastasis was confirmed histologically in 50.5%. Multiple tumor formation was seen in 42.8% of patients. In this group, the rate of recurrence was 2.7% at 5 years and 5.0% at 8 years after surgery. Our preliminary data suggest that papillary microcarcinomas do not frequently become clinically apparent, and that patients can choose observation while their tumors are not progressing, although they are pathologically multifocal and involve lymph nodes in high incidence.

Expression of α1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation

Previous studies have demonstrated that terminal fucosylation is associated with the biological aggressiveness of carcinomas, but the significance of core fucosylation (alpha1,6-fucosylation) through alpha1,6-fucosyltransferase (FUT8) has not been studied in depth. Herein, we investigated the expression of alpha1,6-fucosyltransferase (FUT8) in 133 cases of thyroid carcinomas using an immunohistochemical approach. The expression of FUT8 was quite low in normal follicules. A high expression of FUT8 was observed in 33.3% of papillary carcinoma and the incidence was directly linked to tumor size and lymph node metastasis. In contrast, this phenomenon was less frequently observed in follicular carcinoma and anaplastic (undifferentiated) carcinoma. These results suggest that FUT8 expression may be a key factor in the progression of thyroid papillary carcinomas, but not follicular carcinomas, and decreases in FUT8 expression might be linked to anaplastic transformation.

Prognosis After Reoperation for Local Recurrence of Papillary Thyroid Carcinoma

PurposeTo investigate the factors associated with a favorable prognosis after reoperation for local recurrent papillary thyroid carcinoma (PTC), we reviewed 45 patients who underwent surgery for first local recurrence of PTC.MethodsWe divided the patients into two groups. Group A (n = 28) had no second recurrence, and group B (n = 17) had second local recurrence after surgery for recurrence.ResultsThe mean follow-up period after reoperation was 56.9 months. The mean age at the time of reoperation in group A was significantly lower than that in group B, at 48.1 years versus 62.3 years, respectively (P = 0.0007). The mean age at the time of the initial operation in group A was also significantly lower than that in group B, at 40.1 years versus 55.1 years, respectively (P = 0.0006). Patients with recurrent tumors only outside the area dissected at the initial operation (n = 27) had a better outcome than those with recurrence within the dissected area (n = 18; P = 0.0127). Patients who underwent systematic partial or modified neck dissection (n = 36) had a better outcome than those who underwent only simple local resection (n = 9; P = 0.0169).ConclusionFor local recurrent PTC, systematic neck dissection is recommended over local resection of recurrent tumors.

Y‐box binding protein expression in thyroid neoplasms: Its linkage with anaplastic transformation

Recent studies have demonstrated that Y‐box binding protein (YB‐1) regulates the transcription of genes linked to carcinoma progression. In this study, we investigated the expression of this protein in thyroid neoplasms to elucidate its significance. The expression of YB‐1 was immunohistochemically investigated using the monoclonal antibody for various thyroid neoplasms. Normal follicles did not overexpress YB‐1, and only moderate overexpression of YB‐1 was observed in some follicular tumors and papillary carcinoma, especially those of a larger size. In contrast, 92.9% of anaplastic carcinoma strongly overexpressed YB‐1. YB‐1 immunoreactivity was seen in both cytoplasms and cell nuclei, but the former was more predominant. These findings suggest that YB‐1 plays a role in regulating the transcription as well as translation of genes contributing to the anaplastic transformation of thyroid carcinoma.

Overexpression of Human Tumor-Associated Antigen, RCAS1, Is Significantly Linked to Dedifferentiation of Thyroid Carcinoma

Objective: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. Methods: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. Results: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). Conclusion: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.

Malignant rhabdoid tumor of the colon: report of a case.

A malignant rhabdoid tumor of the colon is very rare and only three cases have been previously described. A 76-year-old man was admitted to the hospital complaining of epigastralgia. An elastic mass was palpable in the right upper abdomen. A barium enema and endoscopic examination showed a giant gyrate tumor arising from the cecum. Abdominal ultrasonography and a computed tomography scan revealed the tumor to be located in the colon associated with multiple liver metastases and gallbladder stones. A right colectomy and cholecystectomy were thus performed. The tumor was histologically composed of sheets of large round and polygonal nuclei with vesicular chromatin, and abundant acidophilic cytoplasm, often containing hyalin-like inclusion. The cytoplasm was positive for vimentin and neuron-specific enolase, and hyaline globules of the rhabdoid tumor cells stained positive for cytokeratin in some cells. Transmission electron microscopy showed characteristic rhabdoid cells with an aggregation of intermediate filaments. A histologic diagnosis of malignant rhabdoid tumor of the colon was made. The tumor demonstrated several unusual findings for malignant rhabdoid tumors including diploidy by a flow cytometric analysis, and positive nuclear immunohistochemical staining for p53 protein and Ki-67 antigen. We report herein the third known case of a pure colonic rhabdoid tumor.

The protocol and preliminary baseline survey results of the thyroid ultrasound examination in Fukushima [Rapid Communication]

UNLABELLED After the Fukushima nuclear power plant accident on March 11, 2011, the public of Japan became particularly concerned about the possibility of an increased risk of childhood thyroid cancer, similar to what was observed after the Chernobyls accident. Due to serious public health perception, there was an urgency to evaluate the baseline levels of childhood thyroid status in Fukushima prefecture. Therefore we have commenced a thyroid ultrasound examination (TUE) survey of the approximately 360,000 pediatric inhabitants (0 to 18 years of age) who lived in Fukushima at the time of the accident in October 2011. The subjects were divided into three categories according to the standardized diagnostic criteria of ultrasound findings. Category A contained the subjects whose TUE findings were intact or benign. Category B were recommended a confirmatory TUE. Category C was recommended an immediate confirmatory TUE. RESULTS The survey of 40,302 subjects in the first year was completed in March, 2013. There were 40,097 (99.5%), 205 (0.50%) and 0 subjects in categories A, B and C, respectively. Of the 82 category B subjects who underwent fine needle aspiration cytology (FNAC), 12 were diagnosed with a malignant tumor or were suspected to have malignancy. The 12 subjects received thyroid surgery and 11 thyroid cancers and one benign nodule were confirmed histologically after surgery. This is the first large-scaled TUE survey to employ sophisticated ultrasound screening and aim to evaluate the baseline frequency of childhood thyroid nodules and cysts. The results will become the golden standard of future comparative TUE in Fukushima, Japan.

Encapsulated Anaplastic Thyroid Carcinoma Without Invasive Phenotype with Favorable Prognosis : Report of a Case

Abstract.We herein report a case of anaplastic thyroid carcinoma in a 77-year-old woman with long-term disease-free survival. The tumor measured 7.5 × 6.0 cm in size and was diagnosed to be anaplastic carcinoma. We investigated the biological aggressiveness of this carcinoma by means of immunohistochemistry and found it have a high cell-proliferating activity, a disruption in the mechanism of apoptosis, and a high potential of cell spreading, similar to that observed in usual anaplastic carcinomas. The only unique point was that this tumor was encapsulated and no invasion of carcinoma cells beyond the capsule was microscopically observed. To avoid an obstruction of the trachea, a lobectomy without lymph node dissection was performed as a “palliative operation.” Although neither adjuvant chemotherapy nor radiotherapy was carried out due to her age, she has nevertheless survived with no evidence of recurrence for 57 months after surgery. The presence of such a type of anplastic carcinoma should thus be noted by surgeons and pathologists, even though the occurrence of such cases seems to be very rare.

p130 expression in thyroid neoplasms: its linkage with tumor size and dedifferentiation

p130 belongs to the retinoblastoma-related gene family, and its gene product works to negatively regulate cell cycle progression in the G1 phase. In this study, we investigated p130 expression in thyroid neoplasms. p130 overexpression was observed in 33.3% of follicular adenoma and 50% of follicular carcinoma and the incidences were not significantly different. In papillary carcinoma, it was overexpressed in 36.5% of cases, but in microcarcinoma, the incidence was significantly lower (14.3%). Furthermore, in anapalstic carcinoma, p130 overexpression was less frequently seen than in papillary carcinoma except for microcarcinoma and follicular carcinoma, and only 14.3% of cases overexpressed this protein. These findings suggest that: (1) reduced p130 expression may contribute to the aggressive character of anplastic carcinoma; and (2) p130 may specify the growth characteristics of microcarcinoma.