Background
The incidence of thyroid cancer is increasing globally. This is mainly due to the increase in the detection of small papillary carcinomas, including papillary microcarcinomas (PMC) 1 cm or ...smaller. It was suggested recently that PMCs are overdiagnosed and overtreated.
Methods
In 1993, the author proposed a clinical trial to compare surgery and observation for low-risk PMC at doctors’ meeting in Kuma Hospital, which was approved and the trial started in the same year. Patients choose immediate surgery or observation. This paper shares our 22-year experience with the active surveillance of more than 2000 patients with low-risk PMC and compares the outcomes of immediate surgery with that of active observation.
Results
The oncological outcomes of these management groups were similarly excellent. In our active surveillance trial on 1235 patients, 8 % of patients showed tumor enlargement by 3 mm or more at 10 years of observation, and 3.8 % of the patients showed novel appearance of lymph node metastasis at 10 years. Patients 40 years or younger tended to show progression of the disease. Patients with these slight progressions of the disease were successfully treated with a rescue surgery. None of the patients in both study groups died of the disease. However, incidences of unfavorable events, such as temporary vocal cord paralysis (VCP) and temporary and permanent hypoparathyroidism, were significantly higher in the immediate surgery group than in the observation group (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 in two of the surgery group.
Conclusions
As a result, although we still offer two options, immediate surgery or observation, to patients with low-risk PMC at Kuma Hospital, we now strongly recommend observation as the best choice.
We showed previously that subclinical low-risk papillary thyroid microcarcinoma (PTMC) could be observed without immediate surgery. Patient age is an important prognostic factor of clinical papillary ...thyroid carcinoma (PTC). In this study, we investigated how patient age influences the observation of low-risk PTMC.
Between 1993 and 2011, 1235 patients with low-risk PTMC chose observation without immediate surgery. They were followed periodically with ultrasound examinations. These patients were enrolled in this study. We divided them into three subsets based on age at the beginning of observation: young (<40 years), middle-aged (40-59 years), and old patients (≥60 years). Observation periods ranged from 18 to 227 months (average 75 months).
We set three parameters for the evaluation of PTMC progression: (i) size enlargement, (ii) novel appearance of lymph-node metastasis, and (iii) progression to clinical disease (tumor size reaching 12 mm or larger, or novel appearance of nodal metastasis). The proportion of patients with PTMC progression was lowest in the old patients and highest in the young patients. On multivariate analysis, young age was an independent predictor of PTMC progression. However, none of the 1235 patients showed distant metastasis or died of PTC during observation. Although only 51 patients (4%) underwent thyrotropin (TSH) suppression based on physician preference, the PTMC of all patients enrolled in this TSH suppression study, except one, were clinically stable. To date, 191 patients underwent surgery for various reasons after observation. None showed recurrence except for one in the residual thyroid, and none died of PTC after surgery.
Old patients with subclinical low-risk PTMC may be the best candidates for observation. Although PTMC in young patients may be more progressive than in older patients, it might not be too late to perform surgery after subclinical PTMC has progressed to clinical disease, regardless of patient age.
Introduction
Papillary thyroid carcinoma (PTC) generally shows an excellent prognosis except in cases with aggressive backgrounds or clinicopathological features. Although the cause-specific survival ...(CSS) of PTC patients has been extensively investigated, the overall survival (OS) of these patients is unclear. We herein investigated both the OS and CSS of a large PTC patient series.
Materials and methods
We enrolled 5897 PTC patients who underwent initial surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years). Their median postoperative follow-up period was 177 months. Univariate and multivariate analyses for OS and CSS assessed the effects of gender, older age (≥55 years), distant metastasis at diagnosis (
M
1), significant extrathyroid extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (
N
≥ 3 cm), and extranodal tumor extension.
Results
To date, 387 patients (7%) in this series have died from various causes, including 117 (2%) due to PTC. The 10-, 15-, and 20-year OS rates are 97, 95, and 90%, respectively. Older age and
M
1 were important prognostic factors for OS and CSS. Older age was a more significant factor than
M
1 for OS and vice versa for CSS. In the older patients,
M
1 was a prominent prognostic factor for both OS and CSS. In the young patients,
M
1 had less prognostic impact than in the older patients, and the prognostic values of
M
1 and
N
≥ 3 cm for OS and CSS were identical and similar, respectively.
Conclusions
The most important prognostic value for OS was patient age, indicating that PTC is generally indolent. However, the control of distant metastasis in older patients remains a future challenge in order to further improve their OS and CSS. PTC of ≥3 cm in young patients should be carefully followed, even in the absence of metastases, and these patients should undergo aggressive therapies for recurrent lesions and metastases.
The 2015 American Thyroid Association thyroid cancer management guidelines endorse an active surveillance management approach as an alternative to immediate biopsy and surgery in subcentimeter ...thyroid nodules with highly suspicious ultrasonographic characteristics and in cytologically confirmed very low risk papillary thyroid cancer (PTC). However, the guidelines provide no specific recommendations with regard to the optimal selection of patients for an active surveillance management approach. This article describes a risk-stratified clinical decision-making framework that was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma (PMC) who were being evaluated for an active surveillance management approach in the United States.
A risk-stratified approach to the evaluation of patients with probable or proven PMC being considered for an active surveillance management approach requires an evaluation of three interrelated but distinct domains: (i) tumor/neck ultrasound characteristics (e.g., size of the primary tumor, the location of the tumor within the thyroid gland); (ii) patient characteristics (e.g., age, comorbidities, willingness to accept observation); and (iii) medical team characteristics (e.g., availability and experience of the multidisciplinary team). Based on an analysis of the critical factors within each of these domains, patients with probable or proven PTC can then be classified as ideal, appropriate, or inappropriate candidates for active surveillance.
Risk stratification utilizing the proposed decision-making framework will improve the ability of clinicians to recognize individual patients with proven or probable PMC who are most likely to benefit from an active surveillance management option while at the same time identifying patients with proven or probable PMC that would be better served with an upfront biopsy and surgical management approach.
Background:
The question of how to manage patients with low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0) has recently become an important clinical issue. Two Japanese centers have conducted ...prospective clinical trials of active surveillance (AS) for low-risk PTMC since the 1990s, reporting favorable outcomes. This policy has thus seen gradual adoption worldwide to avoid overtreatment. Not all PTMCs are suitable for AS, however, and many physicians still hesitate to apply the management policy in daily clinical practice. A task force on management for PTMC created by the Japan Association of Endocrine Surgery collected and analyzed bibliographic evidence and has produced the present consensus statements regarding indications and concrete strategies for AS to facilitate the management of adult patients diagnosed with low-risk PTMC.
Summary:
These statements provide indications for AS in adult patients with T1aN0M0 low-risk PTMC. PTMCs with clinical lymph node metastasis, distant metastasis, recurrent laryngeal nerve (RLN) paralysis due to carcinoma invasion, or protrusion into the tracheal lumen warrant immediate surgery. Tumors suspected of aggressive subtypes on cytology are recommended for immediate surgery. Immediate surgery is also recommended for tumors adherent to the trachea or located along the course of the RLN. Practical strategies include diagnosis, decision-making, follow-up, and monitoring related to the implementation of AS. The rate of low-risk PTMC progression is lower in older patients. However, we recommend continuing AS as long as circumstances permit. Future tasks in optimizing management for low-risk PTMC are also described, including molecular markers and patient-reported outcomes.
Conclusions:
An appropriate multidisciplinary team is necessary to accurately evaluate primary tumors and lymph nodes at the beginning of and during AS, and to adequately reach a shared-decision with individual patients. If appropriately applied, AS of low-risk PTMC is a safe management strategy offering favorable outcomes and preserves quality of life at low cost.
Background:
Agranulocytosis is a rare but serious complication of antithyroid drug (ATD) therapy. Characteristics of agranulocytosis have been reported in only a small number of patients.
Method:
We ...studied 754 cases of ATD-induced agranulocytosis reported over 30 years. The age distribution and sex ratio were compared with those in 12 503 untreated Graves' patients at Kuma Hospital. The annual number of new Graves' patients in Japan was estimated from the Japan Medical Data Center Data Mart-Pharmacovigilance health insurance receipt database.
Results:
Agranulocytosis developed within 90 days after starting ATD therapy in most patients (84.5%). The methimazole dose given at onset was 25.2 ± 12.8 mg/d (mean ± SD). The mean age was 43.4 ± 15.2 years, and the male to female ratio was 1:6.3. When compared with patients at Kuma Hospital, patients with agranulocytosis were older (P < .001) and more females (P < .0001). Of 211 patients with more than 1 granulocyte measurement before onset, 131 (62%) showed normal counts (>1000/μL) within 2 weeks before onset, demonstrating real sudden onset of agranulocytosis. In contrast, some of the 20 patients with more than 4 measurements showed gradual decreases in granulocyte counts. Analysis of physician reports for 30 fatal cases revealed that some deaths might have been prevented. The number of new Graves' patients treated with ATD was estimated at about 35 000 per year, and the incidence rate of agranulocytosis was 0.1% to 0.15% in Japan.
Conclusion:
This is the largest study of agranulocytosis. Agranulocytosis tends to occur abruptly within 3 months after initiation of ATD therapy, although it develops gradually in some patients. Providing every patient with sufficient information on agranulocytosis is critical.
Differentiated thyroid carcinoma originates from thyroid follicular cells and is the most prominent malignancy of the endocrine organs. There are two histological types of differentiated carcinoma, ...namely, papillary and follicular carcinoma. According to reports from Western countries, papillary carcinoma comprises 85.3% of thyroid malignancies in whites, and 72.3% in blacks 1, 2. In Japan, a previous study showed that the prevalence of papillary carcinoma was 78.4% based on material registered between 1977 and 1986 3, but according to recent findings reported in 2004 by Japanese Society of Thyroid Surgeons (JSTS), papillary carcinoma accounted for as much as 93% of all thyroid carcinomas. Papillary carcinoma frequently metastasizes to the regional lymph node and shows multicentricity in the thyroid gland. It usually shows a typical ultrasonographic appearance and can be rather easily diagnosed by fine needle aspiration biopsy (FNAB) 4-6. Follicular carcinoma accounts for 10.9-20.5% of the patients in the United States 1, 2. In Japan, the prevalence of follicular carcinoma was reported to be 17.2% 3, but it decreased to 5% in a report by JSTS in 2004. This carcinoma is only occasionally diagnosed preoperatively, because it is hard to discriminate follicular carcinoma from benign adenoma on imaging studies and cytologic findings. In contrast to papillary carcinoma, follicular carcinoma more often metastasizes to distant organs than regional lymph nodes. In Japan, the prevalence of papillary carcinoma increased and that of follicular carcinoma decreased between reports from 1977 to 1986 and that in 2004, which may be because follicular variant of papillary carcinoma was classified into follicular carcinoma in the previous results. Generally, these carcinomas show an indolent character, but when the lesion dedifferentiates and becomes undifferentiated carcinoma, it displays very rapid growth with an adverse prognosis and is regarded even as the most aggressive malignancy among human solid carcinomas 7, 8. Furthermore, cases showing certain characteristics are likely to be constantly progressive and even become life-threatening. Such cases should be regarded as "high-risk" requiring careful and extensive surgical treatment and postoperative follow-up. Indeed, it is most important for physicians to correctly distinguish high-risk cases from those with an indolent character, although how to evaluate the biological characteristics of thyroid carcinoma and how to identify high-risk cases remains highly controversial. In this review, the methods of distinguishing high-risk cases and the appropriate therapeutic strategies for papillary and follicular carcinomas predominantly based on our experience are emphasized and our proposals for therapies including surgical treatment are demonstrated.
The incidence of thyroid cancer is increasing rapidly in many countries, resulting in rising societal costs of the care of thyroid cancer. We reported that the active surveillance of low-risk ...papillary microcarcinoma had less unfavorable events than immediate surgery, while the oncological outcomes of these managements were similarly excellent. Here we calculated the medical costs of these two managements. We created a model of the flow of these managements, based on our previous study. The flow and costs include the step of diagnosis, surgery, prescription of medicine, recurrence, salvage surgery for recurrence, and care for 10 years after the diagnosis. The costs were calculated according to the typical clinical practices at Kuma Hospital performed under the Japanese Health Care Insurance System. If conversion surgeries were not considered, the ‘simple cost’ of active surveillance for 10 years was 167,780 yen/patient. If there were no recurrences, the ‘simple cost’ of immediate surgery was calculated as 794,770 yen/patient to 1,086,070 yen/patient, depending on the type of surgery and postoperative medication. The ‘simple cost’ of surgery was 4.7 to 6.5 times the ‘simple cost’ of surveillance. When conversion surgeries and recurrence were considered, the ‘total cost’ of active surveillance for 10 years became 225,695 yen/patient. When recurrence were considered, the ‘total cost’ of immediate surgery was 928,094 yen/patient, which was 4.1 times the ‘total cost’ of the active surveillance. At Kuma Hospital in Japan, the 10-year total cost of immediate surgery was 4.1 times expensive than active surveillance.
The global incidence of small papillary thyroid carcinoma (PTC) is increasing remarkably, mostly due to the increased use of imaging studies worldwide. The issue of how to manage low-risk small PTC ...has become urgent. In this review, we focus on how to treat low-risk papillary thyroid microcarcinomas (PMCs; i.e., PTCs measuring ≤10 mm).
Studies of large numbers of patients with low-risk PMC clarified that most of the PMCs did not grow or grew very slowly and were harmless. Active observations of these patients discriminated rare progressive cases from the majority. Surgery performed after the detection of progression signs was not too late, and surgery immediately after the detection and diagnosis of low-risk PMC may be overtreatment for most patients. Interestingly, low-risk PMCs in elderly patients were most unlikely to progress, in sharp contrast to clinical PTC. The reason for this phenomenon remains unknown.
Active observation without immediate surgery can be a leading alternative to the classical surgical treatment in the majority of the patients with low-risk PMC. It is not too late to perform surgery after the detection of progression signs for these patients.
http://links.lww.com/COON/A10
The burden of concern for patients with thyroid cancer who undergo surgical intervention with or without radioactive iodine is known to be substantial. For patients under active surveillance, this ...aspect of the patient experience has not been described to date and could be a potential barrier to broader acceptance of surveillance as a cancer management strategy.
To describe the experiences of patients in the longest-standing and largest thyroid cancer active surveillance program.
This study used a mixed method of survey, semistructured interviews, and field observation and was conducted at Kuma Hospital in Kobe, Japan. The survey was administered from September 4, 2017, through October 18, 2017, and the field observation was conducted from August 28, 2017, to October 20, 2017. Survey participants were a consecutive sample of 249 patients under active surveillance who were attending the hospital for a surveillance visit, and the semistructured interviewees were a subset of 21 patients. The English-language survey instrument was translated by native Japanese speakers, back-translated into English, and then further refined by a panel of Japanese speakers with expertise in health research.
Survey and interview responses and field observations.
In total, 249 surveys were distributed to patients with thyroid cancer on active surveillance. Two hundred forty-three patients (97.6%) completed the survey. Among the respondents, 195 (80.2%) were female and 20 (8.2%) were male (28 11.5% responses were missing). Among the subset of 21 patients who participated in the semistructured interview, 3 were male (14.3%), and the mean (range) age was 64 (32-85) years. Thirty-seven percent rated the frequency of cancer worry as occurring sometimes or more. Thirty-two percent said their worry affected their mood somewhat or a lot. Fourteen percent reported that their worry affected their ability to carry out daily activities somewhat or a lot. Cancer spread, later need for surgical intervention, and difficulty with interpreting bodily experiences in the general location of the cancer were among the main sources of worry. Most respondents (60.0%) said their worry was less than it was when they first found out about their cancer. By 3 years after diagnosis, the proportion of participants who reported they were not at all worried increased from 14% (95% CI, 12%-16%) to 25% (95% CI, 23%-26%). Eighty percent (95% CI, 79%-81%) of respondents agreed or strongly agreed that their decision to do active surveillance matched their personal values, and 83% (95% CI, 82%-84%) agreed or strongly agreed that choosing active surveillance was the best decision for them personally. Most patients (77%) had not heard of active surveillance before they were offered the option.
Cancer concern was common among patients with thyroid cancer under active surveillance, which is comparable to the worry among actively treated patients. Levels of cancer worry reported by patients under active surveillance decreased over time, and patients expressed satisfaction with their disease management decision. These findings suggest that the possibility of cancer worry should not be viewed as prohibitive to successful active surveillance in thyroid cancer.
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