Akifumi Suzuki

Thyroid Lobectomy for Papillary Thyroid Cancer: Long-term Follow-up Study of 1,088 Cases

BackgroundTotal thyroidectomy is well accepted as initial surgery for papillary thyroid cancer (PTC), but the extent of the thyroidectomy remains a matter of controversy. This study was designed to investigate the long-term clinical outcome of PTC patients who had undergone thyroid lobectomy and to elucidate the indications of lobectomy as initial surgery.MethodsThe cases of 1,088 PTC patients who underwent thyroid lobectomy with curative intent at Ito Hospital between 1986 and 1995 were analyzed retrospectively in this study. None of the patients had received postoperative radioactive iodine (RAI) ablation therapy. The median follow-up period was 17.6xa0years. All clinical outcomes, including recurrence and death as a result of PTC or other reasons, were evaluated. To establish the indications for lobectomy as initial surgery for PTC, the potential risk factors, such as age, sex, primary tumor size, extrathyroidal invasion, and clinical lymph node metastasis at the time of the initial surgery, were assessed statistically for associations with recurrence and disease-related death.ResultsThe remnant-thyroid recurrence-free survival (RT-RFS) rate, the regional- lymph-node recurrence-free survival (L-RFS) rate, and the distant-recurrence-free survival (D-RFS) rate as of 25xa0years after surgery were 93.5, 90.6, and 93.6%, respectively. The cause-specific survival (CSS) rate at 25xa0years was 95.2%. Univariate and multivariate analyses showed that none of the factors assessed were significantly associated with the RT-RFS rate. Tumor size, clinical lymph node metastasis, and extrathyroidal invasion were significantly associated with the L-RFS rate. The D-RFS and CSS rates were both significantly lower in the group of patients who were aged 45xa0years old or older, the group whose tumors were larger than 40xa0mm, and the group with extrathyroidal invasion. Based on the above findings, we classified the patients into four groups according to age <45 or ≥45xa0years, tumor size ≤40 or >40xa0mm, whether clinical lymph node metastasis was present, and whether extrathyroidal invasion was present. None of the patients without any of these four risk factors died of PTC. On the other hand, 22 patients who died of PTC were positive for one or more of these four factors.ConclusionsThe long-term clinical outcome of the PTC patients who had been treated by lobectomy without RAI ablation was excellent. Based on the above results, we concluded that lobectomy is a valid alternative to total thyroidectomy for the treatment of PTC patients who are younger than aged 45xa0years, whose tumor diameter is 40xa0mm or less, and who do not have clinical lymph node metastasis or extrathyroidal invasion.

Outcomes and Prognostic Factors of 251 Patients with Minimally Invasive Follicular Thyroid Carcinoma

BACKGROUNDnRadioiodine ablation after total thyroidectomy is the generally accepted treatment for patients with widely invasive follicular thyroid carcinoma (FTC). The therapeutic strategy for minimally invasive FTC, on the other hand, is still a matter of controversy. The histological diagnosis of minimally invasive FTC is often made after lobectomy. The aim of this study was to determine the factors associated with the development of distant metastases in patients with minimally invasive FTC.nnnMETHODSnBetween 1989 and 2006, 251 patients with minimally invasive FTC underwent initial surgery at our hospital. Their median follow-up period was 7.2 years. There were 194 women and 57 men. Their mean age at the time of surgery was 46 years. Distant metastases were diagnosed in 54 patients (21.5%). In 22 of them distant metastases were diagnosed at the time of the initial surgery (M1), and in the other 32 they were diagnosed during the follow-up period. Age at initial surgery, sex, primary tumor size, histological findings (differentiation, and extent of vascular and capsular invasion), completion total thyroidectomy, and distant metastases at initial surgery were assessed as prognostic factors for distant-metastases-free survival (DMFS) and cause-specific survival (CSS). The Kaplan-Meier method and log-rank test were used to analyze time-dependent variables. The Cox proportional hazard model was used to perform the multivariate analysis.nnnRESULTSnUnivariate analysis showed that age (45 years or older) and primary tumor size (4 cm or more) were significant prognostic factors related to postoperative distant metastases in the group of 229 patients without distant metastases at time of the initial surgery. The cumulative survival rate was significantly poorer in M1 patients, patients aged 45 years or older, and patients whose primary tumor size was 4 cm or more. Multivariate analysis showed that age was a significant prognostic factor both for DMFS and CSS.nnnCONCLUSIONSnAge was the most powerful prognostic factor for patients with minimally invasive follicular thyroid cancer. The prognoses of patients younger than 45 years old were excellent and distant metastases rarely occurred. Routine completion total thyroidectomy and radioiodine ablation is thought unnecessary for these patients.

Does Hürthle Cell Carcinoma of the Thyroid Have a Poorer Prognosis than Ordinary Follicular Thyroid Carcinoma

BackgroundHürthle cell carcinoma (HCC) is a rare form of thyroid carcinoma and is considered an oxyphilic variant of follicular thyroid carcinoma. However, little is known about its biological characteristics or clinical behavior. We conducted a retrospective study to determine whether the prognosis of HCC differs from that of ordinary follicular thyroid carcinoma (OFC).MethodsThe subjects were the 558 patients with follicular thyroid carcinoma who underwent initial surgery at our institution between 1989 and 2010 and consisted of 73 patients with HCC and 485 patients with OFC. There were 410 females and 148 males, and their median age was 51xa0years. A univariate analysis was conducted in relation to cumulative cause-specific survival (CSS) according to the Kaplan–Meier method for the following variables: age at the time of initial surgery, gender, tumor size, invasiveness, distant metastasis at presentation, and histological type (HCC vs OFC). Differences between groups were analyzed for significance by the log-rank test. Multivariate analysis was performed by using the Cox proportional hazard model.ResultsA total of 4 patients (5.5xa0%) in the HCC group had distant metastasis compared with 106 patients (21.9xa0%) in the OFC group. Significant factors in relation to CSS in the univariate analyses were age, tumor size, and invasiveness, but there were no significant differences between the HCC group and the OFC group. Multivariate analysis showed that age, tumor size, and distant metastasis at presentation were significant factors.ConclusionsHCC does not have a poorer prognosis than OFC.

Papillary Thyroid Carcinoma in Children and Adolescents: Long-Term Follow-Up and Clinical Characteristics

BackgroundThe aim of this study was to analyze the clinical features and clinical outcomes of papillary thyroid carcinoma (PTC) in the pediatric and adolescent population treated in our institution.MethodsThe subjects were 227 PTC patients 20xa0years of age or under treated initially between 1979 and 2012. Their mean age at diagnosis was 18-year old (range 7–20xa0years). Patient characteristics and outcomes in the period before 1999 and the period after 2000 were compared. Cause-specific survival (CSS) rates and disease-free survival (DFS) rates were calculated by the Kaplan–Meier method.ResultsTwo patients died of their disease and 45 patients had recurrent disease (36 in lymph node, seven in a remnant thyroid, and 11 in the form of distant metastasis). The 10-, 20-, and 30-CSS rates were 99.3, 99.3, and 96.5xa0%, respectively, and the 10-, 20-, and 30-DFS were 83.6, 70.7, and 64.0xa0%, respectively. Gender and preoperative lymph node metastasis were identified as significant factors related to DFS in the multivariate analysis. After the year 2000, there were significantly more patients with a small primary tumor size, significantly more patients without distant metastasis at presentation and significantly more patients without extrathyroidal invasion.ConclusionThe number of patients with advanced cancer has been declining in recent years. Lobectomy with prophylactic unilateral central neck dissection is considered acceptable for patients without the risk factors for recurrence.

Does Completion Thyroidectomy Improve the Outcome of Patients with Minimally Invasive Follicular Carcinoma of the Thyroid

AbstractBackgroundnThe diagnosis of minimally invasive follicular thyroid carcinoma (MIFTC) is often made histologically after thyroid lobectomy. We attempted to determine whether completion thyroidectomy should be considered necessary for all patients diagnosed with MIFTC after thyroid lobectomy.MethodsThe subjects of this study were a total of 324 patients who underwent thyroid lobectomy as initial surgery at our institution between 1989 and 2010 and diagnosed histologically as MIFTC. Completion thyroidectomy was performed on 101 patients, and the other 223 patients were followed up without further treatments. Cumulative cause-specific survival (CSS) rates and distant-metastasis-free survival (DMFS) rates were calculated by the Kaplan–Meier method. Differences between groups were analyzed for statistical significance by the log-rank test. Multivariate analysis was performed by using the Cox proportional hazards model.ResultsDuring the follow-up period, 39 patients were diagnosed with distant metastasis, and 7 patients died of their disease. Age at the initial surgery was found to be a significant factor related to DMFS in both the univariate and multivariate analysis and to also be related to CSS in the univariate analysis. Completion thyroidectomy did not have a significant effect on DMFS or CSS according to the results of the univariate analysis, but it had significant effect on DMFS according to the results of the multivariate analysis.ConclusionsAlthough we were unable to demonstrate sufficient statistical evidence that completion thyroidectomy improved the outcome of MIFTC patients, it is noteworthy none of the patient who underwent completion thyroidectomy died of the disease.

Clinicopathologic Features and Outcomes in Patients with Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

BackgroundDiffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare variant more common among younger patients.Materials and methodsExcluding patients with microcarcinoma, 5848 patients with PTC underwent initial surgery between 1995 and 2011. Twenty-two patients (0.4xa0%) were histologically diagnosed with DSV, of whom 20 (91xa0%) were <45xa0years old. We compared clinicopathologic characteristics and outcomes between patients with DSV and those with classical PTC <45 years old. Univariate analysis by the Kaplan–Meier method in relation to cause-specific survival (CSS) and disease-free survival (DFS) rates was performed with regard to the following variables: sex; anti-thyroglobulin antibody (TgAb) positivity; presence of distant metastasis; pathological lymph node metastasis; extra-thyroidal invasion; and pathological variant (classical vs. DSV).ResultsThe 20 patients with DSV <45xa0years old comprised 18 females and 2 males. Frequencies of TgAb, pN1b, and local recurrence were higher in the DSV group than in the classical PTC group. Ten-year CSS and DFS rates for PTC patients <45xa0years old were 99.7 and 88.6xa0% in the classical PTC group and 100 and 60.5xa0% in the DSV group. CSS rate did not differ between groups, but DFS rate was significantly lower in the DSV group than in the classical PTC group (pxa0<xa00.0001, log-rank test). Multivariate analysis identified DSV group and pN1b as prognostic factors for recurrence in young PTC patients.ConclusionsMost DSV patients were young and had a background of chronic thyroiditis. Outcomes for DSV were very good, but recurrence was more common than in classical PTC.

Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma

Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE.

Antimicrobial prophylaxis for the prevention of surgical site infection after thyroid and parathyroid surgery: a prospective randomized trial.

Background and ObjectiveThe effectiveness of antimicrobial prophylaxis (AMP) in the prevention of surgical site infection (SSI) following thyroid and parathyroid surgery remains uncertain. The objective of this prospective randomized controlled trial (Ito-RCT1) was to assess the effectiveness of AMP in clean neck surgery performed to treat thyroid and parathyroid disease.MethodsParticipants comprised patients scheduled for clean neck surgery for thyroid and parathyroid disease at Ito Hospital. Patients whose surgery included sternotomy or resection of the trachea, larynx, pharynx, or esophagus were excluded. AMP consisted of 2xa0g of piperacillin (PIPC) (group A, nxa0=xa0541) or 1xa0g of cefazolin (CEZ) (group B, nxa0=xa0541) administered intravenously immediately after endotracheal intubation. Patients in the control group (Group C, nxa0=xa01,082) did not receive AMP.ResultsStatistical analysis was performed to compare the AMP group (Group Axa0+xa0Group B) with the control group (Group C). Drug-induced acute reactions correlated to PIPC or CEZ did not occur in the AMP group. No significant differences in the postoperative incidence of liver or renal dysfunction were seen between the AMP and control groups. Postoperative incidence of urinary tract infection was significantly higher in the control group (pxa0=xa00.002). The incidence of SSI events was very low, with only 1 event (0.09xa0%) in the AMP group and 3 events (0.28xa0%) in the control group, and this difference between groups was not significant (pxa0=xa00.371).ConclusionsAMP is not necessary to prevent SSI after clean thyroid or parathyroid surgery.

Chemosensitivity of Anaplastic Thyroid Cancer Based on a Histoculture Drug Response Assay

The chemosensitivity of anaplastic thyroid cancer (ATC) to some cytotoxic agents was investigated by the histoculture drug response assay (HDRA). Thirty specimens from 22 patients with ATC were obtained from surgically resected subjects. The drugs tested were paclitaxel (PTX), docetaxel (DOC), adriamycin (ADM), nedaplatin (254-S), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP-16), 5-fluorouracil (5-FU), mitomycin C (MMC), and cyclophosphamide (CPA). PTX was the most effective agent, and 25 of 29 cases (86.2%) had high inhibition rates (IRs; over 70%), while DOC, another taxane, had lower IRs (median, 32.6%). 254-S had the second highest IR (median 68.1%), higher than other platins, CDDP (median 47.3%) and CBDCA (median 27.4%). The IR of 50% dose PTX (20u2009μg/mL, median 30.6%) was markedly decreased, while that of 50% dose 254-S (10u2009μg/mL, median 63.3%) still retained its inhibition effect compared to 100% dose. Most recurrent samples had higher IRs than primary lesions, but the IRs of different drugs differed between primary and recurrent lesions, even with samples from the same patients. PTX has a higher IR to ATC tissues in the HDRA, which suggests that it may be a key drug for the treatment of patients with ATC.

Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.