Background: The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. Excellent oncological outcomes of active surveillance for low-risk PMC have been reported previously. Here, unfavorable events following active surveillance and surgical treatment for PMC were studied.Methods: From February 2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these, 1179 patients chose active surveillance and 974 patients chose immediate surgery. The oncological outcomes and the incidences of unfavorable events of these groups were analyzed.Results: In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastases were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion to surgery had nodal recurrence, and five patients in the immediate surgery group had a recurrence in a cervical node or unresected thyroid lobe. All of these recurrences were successfully treated. None of the patients had distant metastases, and none died of the disease. The immediate surgery group had significantly higher incidences of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and permanent hypoparathyroidism than the active-surveillance group did (4.1% vs. 0.6%, p < 0.0001; 16.7% vs. 2.8%, p < 0.0001; and 1.6% vs. 0.08%, p < 0.0001, respectively). Permanent VCP occurred only in two patients (0.2%) in the immediate surgery group. The proportion of patients on L-thyroxine for supplemental or thyrotropin (TSH)-suppressive purposes was significantly larger in the immediate surgery group than in the active surveillance group (66.1% vs. 20.7%, p < 0.0001). The immediate surgery group had significantly higher incidences of postsurgical hematoma and surgical scar in the neck compared with the active surveillance group (0.5% vs. 0%, p < 0.05; and 8.0% vs. 100%, p < 0.0001, respectively).Conclusions: The oncological outcomes of the immediate surgery and active surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate surgery group. Thus, active surveillance is now recommended as the best choice for patients with low-risk PMC.

Screening out patients who do not require immediate surgery is a growing trend in the field of thyroid research. In this study, we retrospectively compared the application of two surveillance selection criteria in 1001 patients who had undergone surgical treatment of papillary thyroid microcarcinoma (PTMC): low-risk PTMC characteristics defined by Kuma Hospital and CATO consensus on PTMC management of active surveillance. Treatment outcomes were compared between groups. We then analyzed the prognostic indicators of patients who could be managed by surveillance. A total of 724 patients met Kuma screening criteria and 135 met CATO screening criteria. The Kuma low-risk group had a lower incidence of multifocal lesions and CLNM than Kuma high-risk group. We also found more obvious differences in multifocal lesions, CLNM and extrathyroidal extension when evaluating the CATO low-risk criteria in the same manner. On the other hand, patients in the CATO low-risk group had a lower disease progression rate and longer disease-free survival than those in CATO high-risk group. There was no significant difference in prognosis between the Kuma low-risk group and Kuma high-risk group. Our logistic regression analysis showed that a preoperative ultrasound size of >5 mm, male sex, younger age, and malignant lesions without concurrent benign nodules could be predictors of CLNM. In conclusion, patients classified in CATO low-risk criteria had lower proportion of clinicopathological risk factors than the ones in Kuma low-risk criteria. We also found more risk factors may not be suitable for surveillance, such as tumors without concurrent benign nodules.

Background: Rapid increases in the incidence of thyroid carcinoma with stable mortality rates from thyroid carcinoma have been reported from many countries, and these increases are thought to be due mostly to the increased detection of small papillary thyroid carcinomas (PTCs), including papillary microcarcinomas (PMCs; i.e., PTCs ≤10 mm). Some researchers have suggested that small PTCs have been overdiagnosed and overtreated. In Japan, the active surveillance of patients with low-risk PMCs was initiated by Kuma Hospital (1993) and Tokyo's Cancer Institute Hospital (1995) based on the extremely higher incidences of both latent thyroid carcinomas in autopsy studies and small PTCs detected in mass screening studies using ultrasound examinations compared to the prevalence of clinical thyroid carcinomas.Methods: The above two institutions' data are summarized regarding the active surveillance of low-risk PMCs, and future prospects for their management are discussed.Results: At 10-year observations in the Kuma Hospital series of 1235 patients, only 8% and 3.8% of the PMC patients showed size enlargement by ≥3 mm and the novel appearance of node metastasis, respectively. In contrast to clinical PTC, PMCs are most unlikely to grow in older patients (≥60 years). In the Kuma Hospital series, the 974 patients who underwent immediate surgery had significantly higher incidences of unfavorable events than the 1179 patients who chose active surveillance. The total cost of immediate surgery, including the costs for salvage surgery and postoperative care for 10 years, was 4.1 times the total cost of 10-year management by active surveillance. Only 8% of the 51 PMC patients showed tumor enlargement during pregnancy, and the rescue surgeries after delivery were successful. In the Cancer Institute Hospital series of 230 patients with 300 lesions, only 7% and 1% of the patients showed size enlargement and novel node metastasis, respectively, and that institution's analysis also revealed that macroscopic or rim calcification and poor vascularity were correlated with non-progressing disease. In both series, none of the patients who underwent rescue surgery after progression signs were detected showed significant recurrence or died of PTC.Conclusion: Active surveillance of low-risk PMC can be the first-line management. Interestingly, older patients with low-risk PMCs are the best candidates for active surveillance.

The estimated lifetime disease progression probabilities of papillary microcarcinoma during active surveillance vary greatly according to the age at presentation.

Background: We report on the growth of papillary microcarcinoma during active surveillance and before clinical presentation. Methods: We conducted a retrospective study of 169 patients with papillary microcarcinoma who were enrolled in active surveillance at our hospital between 20 0 0 and 2004. Patients were followed for a median of 10.1 years using serial ultrasonography (median, 12 examinations), used to calculate the tumor doubling time. To contextualize tumor growth rates during active surveillance, we calculated the hypothetical tumor doubling time before clinical presentation. To resolve the limitations in tumor doubling time, tumor doubling rates were inversely transformed into doubling rates. Results: The doubling rates (per year) during active surveillance (median: 0.0) were > 0.5, 0.1 to 0.5, −0.1 to 0.1, and < −0.1 in 5, 38, 97, and 29 cases, respectively. The proportions of tumors with rather rapid growth, slow growth, stable, and a decrease in size were 3%, 22%, 57%, and 17%, respectively. Conclusion: Tumor growth of papillary microcarcinomas varies from rather rapid growth to a decrease in size during active surveillance.

SummarySeveral reports have demonstrated a possible association of periodontal infections with coronary heart disease (CHD) by elevated antibody titre to periodontopathic bacteria in CHD patients compared with non-diseased controls. Although each periodontopathic bacterium may vary in virulence for periodontitis and atherosclerosis, antibody response to multiple bacteria in CHD patients has not been understood fully. Therefore, serum levels of antibody to 12 periodontopathic bacteria together with other atherosclerotic risk markers were compared among 51 patients with CHD, 55 patients with moderate to severe chronic periodontitis and 37 healthy individuals. The antibody response was the most prevalent for Porphyromonas gingivalis, a major causative organism, in CHD as well as periodontitis patients. However, antibody positivity was different between CHD and periodontitis if the response was analysed for two different strains of P. gingivalis, namely FDC381 and Su63. While periodontitis patients were positive for both P. gingivalis FDC381 and Su63, a high frequency of antibody positivity for P. gingivalis Su63 but not for FDC381 was observed in CHD patients. The results indicate that the presence of particular periodontopathic bacteria with high virulence may affect atherogenesis. Identifying the virulence factors of P. gingivalis Su63 may gain insight into the new therapeutic modality for infection-induced deterioration of atherosclerosis.

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Among PMCs that touched the TR or were located in the course of the RN, observation could be the first choice for tumors < 7 mm and those ≥ 7 mm judged as low risk for TR or RN invasion. However, for PMCs with high-risk features, immediate surgery after cytological diagnosis by a needle aspiration biopsy is recommended.