Risk factors for mediastinal lymph node metastasis and lung metastasis in papillary thyroid carcinoma patients: who benefits from preoperative computed tomography?

In papillary thyroid carcinoma (PTC) patients with mediastinal lymph nodes (LN) and lung metastases, adding preoperative computed tomography (CT) to ultrasound is useful for planning surgery. We identified risk factors (RFs) for mediastinal lymph node metastasis (MLNM) and lung metastasis in PTC patients. Frequencies of MLNM and lung metastases were compared in 478 patients. Relative risk (RR) was calculated based on RFs. MLNM and lung metastases were detected in 1.2% and 3.3% of patients, respectively. cT3-4, cN1, central LN metastasis, and lateral LN metastasis were RFs for MLNM in all patients (p < 0.05, p < 0.05, p < 0.05, p < 0.01) and older patients (age: ≥55 years) (p < 0.01, p < 0.05, p < 0.05, p < 0.05). cT3-4, cN1, gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs for lung metastasis in all patients (p < 0.01, p < 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). cN1 and gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs in older patients (p < 0.01, p < 0.01, p < 0.05, p < 0.01), while lateral LN metastasis was an RF for lung metastasis in those of <55 years of age (younger patients) (p < 0.05). No MLNM was observed in cT1-2cN0 PTC patients, who accounted for 50.5% of patients included in the MLNM analysis. No lung metastasis was present in cT1-2cN0 PTC patients, who accounted for 50.5% of the patients included in the lung metastasis analysis. PTC patients with cT3-4 and cN1 have an increased risk of MLNM and lung metastasis. RFs differed between older and younger patients. Preoperative neck and chest CT are not necessary for PTC patients with ultrasound-diagnosed as cT1-2cN0.

Size-Dependent Corrosion of Al-Fe Intermetallic Particles at Al-Mg Alloy Surfaces Investigated by In-Liquid Nanoscale Potential Measurement Technique.

Corrosion of Al alloy often starts from the nanoscale corrosion around the surface-exposed Al-Fe intermetallic particles (IMPs) and leads to a serious damage limiting its application range in the automobile industry. To solve this issue, understanding of the nanoscale corrosion mechanism around the IMP is essential, yet it is impeded by the difficulties in directly visualizing nanoscale distribution of reaction activity. Here, this difficulty is overcomed by open-loop electric potential microscopy (OL-EPM) and investigate nanoscale corrosion behavior around the IMPs in H2 SO4 solution. The OL-EPM results reveal that the corrosion around a small IMP settles down in a short time (<30 min) after transient dissolution of the IMP surface while that around a large IMP lasts for a long time especially at its edges and results in a severe damage of the IMP and matrix. This result suggests that an Al alloy with many small IMPs gives a better corrosion resistance than that with few large IMPs if the total Fe content is the same. This difference is confirmed by corrosion weight loss test using Al alloys with different IMP sizes. This finding should give an important guideline to improve the corrosion resistance of Al alloy.

Outcomes of Patients with an Intermediate-Risk Group According to the Japanese Risk Classification of Papillary Thyroid Carcinoma.

BACKGROUND: The management of intermediate-risk group of papillary thyroid cancer (PTC) is still vague, particularly regarding whether or not total thyroidectomy, postoperative radioactive iodine ablation (RAI-a), and postoperative TSH suppression are mandatory. METHODS: This retrospective study evaluated 680 PTC patients from 2010 to 2017, who were classified into the three risk groups as low, intermediate, and high-risk groups according to the criteria of the Japanese Association of Endocrine Surgeons (JAES) 2010 and underwent surgery according to the JAES guidelines. We retrospectively collected patient data for analyses of disease-free survivals in the intermediate-risk group patients. RESULTS: We performed surgery on 680 PTC patients from 2010 to 2017. Of them, 297 were classified as the intermediate-risk group. DFS was not statistically significantly different in patients with/without total thyroidectomy and postoperative TSH suppression therapy. For RAI-a, DFS (95% confidence interval) at 3, 5, and 8 years were 93.2% (84.6 ~ 97.2), 81.6% (68,3 ~ 90.2), and 70.7% (51.4 ~ 84.6) in patients with postoperative RAI-a and 100%, 100%, and 100% in patients without postoperative RAI-a after total thyroidectomy, respectively. DFS of patients without RAI-a was superior to those with RAI-a (P < 0.0004). Multivariable analysis by stepwise selection method revealed that postoperative RAI-a was a risk factor with a hazard ratio of 5.69. (95% CI 1.998-16.21) (P = 0.001131). CONCLUSIONS: Our study did not show the efficacy of RAI-a in patients with intermediate-risk PTC. This study implies that judging the efficacy of adjuvant therapy such as RAI or TSh suppression in intermediate-risk patients is difficult.

Diagnosis and management of adrenal incidentaloma: use of clinical judgment and evidence in dialog with the patient.

The prevalence of adrenal incidentaloma (AI) in imaging studies, including those of the adrenal glands, is estimated to be 1-5%. Essential factors for the proper management of AI include a correct diagnosis, adequate surgical skills, appropriate perioperative management, and sound dialogue with the patient. Aside from the possibility of overdiagnosis, patients with apparent signs or symptoms attributable to adrenal hormone excess have reasonable indications for surgery. At the same time, milder patients may be candidates for active surveillance without intervention. Even individuals with nonfunctioning AI may benefit from surgery if imaging studies depict the tumor as suggestive of malignancy. However, a differential diagnosis of AI may not be easy for surgeons with little experience in seeing such patients.Furthermore, a patient without a correct diagnosis may miss the window of opportunity for a cure or incur a greater risk of developing complications, such as adrenal insufficiency or cardiovascular events during or after surgery, due to inadequate management. The clinical practice guidelines for AI from around the world may be helpful for shared decision-making; however, Japan lacks established guidelines. In this review article, we propose practical guidelines relevant to management by summarizing the evidence for five key questions that are often asked in dialog with patients with AI.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study.

INTRODUCTION: Non-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC. MATERIALS AND METHODS: PTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients. RESULTS: Pathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91-8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60-8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs. CONCLUSION: The prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.

The revised clinical practice guidelines on the management of thyroid tumors by the Japan Associations of Endocrine Surgeons: Core questions and recommendations for treatments of thyroid cancer.

The Japan Associations of Endocrine Surgeons has developed the revised version of the Clinical Practice Guidelines for Thyroid Tumors. This article describes the guidelines translated into English for the 35 clinical questions relevant to the therapeutic management of thyroid cancers. The objective of the guidelines is to improve health-related outcomes in patients with thyroid tumors by enabling users to make their practice evidence-based and by minimizing any variations in clinical practice due to gaps in evidential knowledge among physicians. The guidelines give representative flow-charts on the management of papillary, follicular, medullary, and anaplastic thyroid carcinoma, along with recommendations for clinical questions by presenting evidence on the relevant outcomes including benefits, risks, and health conditions from patients' perspective. Therapeutic actions were recommended or not recommended either strongly (◎◎◎ or XXX) based on good evidence (😊)/good expert consensus (+++), or weakly (◎, ◎◎ or X, XX) based on poor evidence (😣)/poor expert consensus (+ or ++). Only 10 of the 51 recommendations given in the guidelines were supported by good evidence, whereas 35 were supported by good expert consensus. While implementing the current guidelines would be of help to achieve the objective, we need further clinical research to make our shared decision making to be more evidence-based.

Effects of surgery on the patient-reported outcomes of primary hyperparathyroidism patients with mild hypercalcemia without classic symptoms: a systematic review of the literature.

PURPOSE: To establish if parathyroidectomy is beneficial for patient-reported outcomes (PROs), including quality of life (QoL), of patients with mild hypercalcemia ( < 1.0 mg/dl above the upper limit of reference ranges) caused by primary hyperparathyroidism without classic symptoms (mild PHPT). METHODS: We conducted a systematic review of the literature. Prospective studies were selected if PROs were measured before and after surgery and if the subpopulation of mild PHPT was clearly defined. Selected studies were appraised for their designs, PRO measures, and potential biases, as well as findings. Effect sizes were estimated to evaluate the extent of the benefits, if possible. RESULTS: Four randomized controlled trials and six observational studies were included in this analysis. Seven studies used the SF-36 to measure QoL and the other three used different scales. Quantitative data on outcomes were provided in the four observational studies, but effect sizes could not be estimated. A placebo effect of surgery was discussed in five studies. Statistically significant improvements in PROs were observed in all studies, but the clinical importance of the changes was not discussed in detail. CONCLUSIONS: The surgical treatment of mild PHPT may be associated with improved PROs, but the clinical significance of the changes is not yet confirmed.

Correlation between urinary fractionated metanephrines in 24-hour and spot urine samples for evaluating the therapeutic effect of metyrosine: a subanalysis of a multicenter, open-label phase I/II study.

We recently conducted an open-label phase I/II study to evaluate the efficacy and safety of preoperative and chronic treatment with metyrosine (an inhibitor of catecholamine synthesis) in pheochromocytoma/paraganglioma (PPGL) in Japan. We compared creatinine-corrected metanephrine fractions in spot urine and 24-hour urine samples (the current standard for the screening and diagnosis of PPGLs) from 16 patients to assess the therapeutic effect of metyrosine. Percent changes from baseline in urinary metanephrine (uMN) or normetanephrine (uNMN) were compared between spot and 24-hour urine samples. Mean percent changes in uMN or uNMN in spot and 24-hour urine were -26.36% and -29.27%, respectively. The difference in the percent change from baseline between uMN or uNMN in spot and 24-hour urine was small (-2.90%). The correlation coefficient was 0.87 for percent changes from baseline between uMN or uNMN measured in spot and 24-hour urine. The area under the receiver operator characteristic (ROC) curve of uMN or uNMN measured in spot urine vs. 24-hour urine (reference standard) to assess the efficacy of metyrosine treatment was 0.93. Correlations and ROCs between 24-hour urinary vanillylmandelic acid, adrenaline, and noradrenaline and 24-hour uMN or uNMN were similar to those between spot uMN or uNMN and 24-hour uMN or uNMN. No large difference was observed between spot and 24-hour urine for the assessment of metyrosine treatment by quantifying uMN or uNMN in Japanese patients with PPGLs. These results suggest that spot urine samples may be useful in assessing the therapeutic effect of metyrosine.

Impact of "Tailored" Parathyroidectomy for Treatment of Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1.

BACKGROUND: Whether total parathyroidectomy (TPTX) or subtotal parathyroidectomy (SPTX) should be performed for primary hyperparathyroidism (PHPT) in patients with multiple endocrine neoplasia type 1 (MEN1) is controversial. At our institution, the parathyroidectomy strategy is based on the number of enlarged intraoperative parathyroid glands. We retrospectively analyzed our parathyroidectomy procedures. METHODS: Data of PHPT treatment in patients with MEN1 who underwent parathyroidectomy from 1982 to 2012 at our department were retrospectively collected. The data were grouped according to the surgical procedure: TPTX, SPTX, and less than SPTX (LPTX). TPTX or SPTX was selected based on the preoperative examination findings and number of enlarged intraoperative parathyroid glands. The outcomes were the disease-free survival (DFS) rate and postoperative calcium replacement rate based on Kaplan-Meier analysis for each type of surgical procedure. RESULTS: Forty-five patients were analyzed. The overall 5- and 10-year DFS was 91.7 and 55.8%, respectively. The 5- and 10-year DFS in each subgroup was 100.0 and 85.7% in the TPTX group, 89.4 and 57.3% in the SPTX group, and 91.6 and 57.3% in the LPTX group, respectively. The postoperative calcium replacement rate at 1 and 12 months was 91.7 and 58.3% in the TPTX group, 21.1 and 7.0% in the SPTX group, and 30.0 and 0.0% in the LPTX group, respectively. CONCLUSIONS: Although LPTX was not satisfactory as a standard procedure, both SPTX and TPTX are effective treatment methods for PHPT in patients with MEN1. The parathyroidectomy strategy should be based on intraoperative evaluation of the parathyroid glands.

Parathyroid carcinoma occurred in two glands in multiple endocrine neoplasia 1: a report on a rare case.

Primary hyperparathyroidism is the most common hormonal manifestation associated with multiple endocrine neoplasia 1 (MEN1). It is generally caused by parathyroid hyperplasia, and parathyroid carcinoma is rare. Here, we report a case of MEN1 with parathyroid carcinoma in two parathyroid glands causing primary hyperparathyroidism. A 40-year-old man with primary hyperparathyroidism due to MEN1 underwent a total parathyroidectomy. His corrected calcium and intact PTH (i-PTH) serum levels were 10.8 mg/dL and 203 pg/mL, respectively. Although three glands were successfully removed, the left upper parathyroid gland could not be detected. Since the right lower parathyroid lesion had invaded into the thyroid, right lobectomy was performed. A portion of the left lower parathyroid tissue was transplanted into his forearm. The histological findings of the left lower and the right upper parathyroid glands were consistent with hyperplasia while that of the right lower parathyroid gland was parathyroid carcinoma. Since the post-surgical i-PTH levels remained high, the intrathyroidal lesion of the left lobe, which was initally diagnosed as an adenomatous nodule, was suspected to contain parathyroid tumor. A fine needle aspiration of the tumor revealed a high concentration of i-PTH. One week after the first surgery, a left thyroid lobectomy was performed. The pathological diagnosis of the tumor was parathyroid carcinoma. After the surgery, calcium and i-PTH levels were normal. Although it is rare, parathyroid carcinoma should be considered as a cause of hyperparathyroidism in MEN1 patients. Since it is difficult to diagnose parathyroid carcinoma before surgery, intraoperative findings are important for the appropriate treatment.

Cohort study exploring the effect of lenvatinib on differentiated thyroid cancer.

Lenvatinib is a molecular-targeting agent that was recently approved in Japan for treatment of curatively unresectable, radioactive iodine-refractory, progressive differentiated thyroid cancer (DTC). Because only a few Japanese patients have received lenvatinib in clinical trials, there are limited domestic data on its safety and efficacy or prognostic factors. Therefore, a prospective observational study has been designed to collect safety and efficacy data in at least 300 patients with curatively unresectable DTC receiving lenvatinib therapy (24 mg/day), in order to find predictors of antitumor activity and survival. Patients with progressive curatively unresectable DTC refractory to radioiodine therapy will be enrolled and the primary endpoint will be overall survival. This study is designed to estimate the 95% confidence intervals of the 1-year and 2-year survival rates with a two-sided width of less than 10%. Secondary endpoints will be the time to treatment failure, time to strategy failure, progression-free survival time with clinical progressive disease, response rate, quality of life, safety, and patient reports. The ultimate goal is to obtain information for developing evidence-based guidelines for treatment of DTC, including recommendations on patient selection, dosages, and duration of treatment. This study has been registered with the UMIN Clinical Trials Registry (UMIN000022243).

Efficacy and safety of metyrosine in pheochromocytoma/paraganglioma: a multi-center trial in Japan.

To assess the efficacy, safety, and pharmacokinetics of metyrosine (an inhibitor of catecholamine synthesis) in patients with pheochromocytoma/paraganglioma (PPGL), we conducted a prospective, multi-center, open-label study at 11 sites in Japan. We recruited PPGL patients aged ≥12 years requiring preoperative or chronic treatment, receiving α-blocker treatment, having baseline urinary metanephrine (uMN) or normetanephrine (uNMN) levels ≥3 times the upper limit of normal values, and having symptoms associated with excess catecholamine. Metyrosine treatment was started at 500 mg/day and modified according to dose-adjustment criteria up to 4,000 mg/day. The main outcome measure was the proportion of patients who achieved at least 50% reduction in uMN or uNMN levels from baseline. Sixteen patients (11 males/5 females) aged 12-86 years participated. After 12 weeks of treatment and at the last evaluation of efficacy, the primary endpoint was achieved in 31.3% of all patients, including 66.7% of those under preoperative treatment and 23.1% of those under chronic treatment. Sedation, anemia, and death were reported in 1 patient each as serious adverse drug reactions during the 24-week treatment. Metyrosine was shown to be tolerated and to relieve symptoms by reducing excess catecholamine in PPGL patients under both preoperative and chronic treatment.

Prediction of lateral pelvic lymph node metastasis from lower rectal cancer using magnetic resonance imaging and risk factors for metastasis: Multicenter study of the Lymph Node Committee of the Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: The goal of the study was to examine prediction of lateral pelvic lymph node (LPLN) metastasis from lower rectal cancer using a logistic model including risk factors for LPLN metastasis and magnetic resonance imaging (MRI) clinical LPLN (cLPLN) status, compared to prediction based on MRI alone. METHODS: The subjects were 272 patients with lower rectal cancer who underwent MRI prior to mesorectal excision combined with LPLN dissection (LPLD) at six institutes. No patients received neoadjuvant therapy. Prediction models for right and left pathological LPLN (pLPLN) metastasis were developed using cLPLN status, histopathological grade, and perirectal lymph node (PRLN) status. For evaluation, data for patients with left LPLD were substituted into the right-side equation and vice versa. RESULTS: Left LPLN metastasis was predicted using the right-side model with accuracy of 86.5%, sensitivity 56.4%, specificity 92.7%, positive predictive value (PPV) 61.1%, and negative predictive value (NPV) 91.2%, while these data using MRI cLPLN status alone were 80.4, 76.9, 81.2, 45.5, and 94.5%, respectively. Similarly, right LPLN metastasis was predicted using the left-side equation with accuracy of 83.8%, sensitivity 57.8%, specificity 90.4%, PPV 60.5%, and NPV 89.4%, and the equivalent data using MRI alone were 78.4, 68.9, 80.8, 47.7, and 91.1%, respectively. The AUCs for the right- and left-side equations were significantly higher than the equivalent AUCs for MRI cLPLN status alone. CONCLUSIONS: A logistic model including risk factors for LPLN metastasis and MRI findings had significantly better performance for prediction of LPLN metastasis compared with a model based on MRI findings alone.

SAFETY AND TOLERABILITY OF VANDETANIB IN JAPANESE PATIENTS WITH MEDULLARY THYROID CANCER: A PHASE I/II OPEN-LABEL STUDY.

OBJECTIVE: In a phase III trial, Western patients with medullary thyroid cancer (MTC) treated with the oral multikinase inhibitor vandetanib showed significantly improved progression-free survival (PFS) and objective response rate (ORR) compared with placebo. The biology of MTC and pharmacokinetics (PK) are similar for Japanese and Western patients; therefore, similar clinical benefit is anticipated in the Japanese population. This study evaluated the safety and tolerability of vandetanib in Japanese patients with unresectable locally advanced or metastatic MTC. METHODS: This was a phase I/II, open-label, nonrandomized study. Patients received vandetanib (300 mg daily) until objective disease progression. The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and PK. Final data analysis was conducted once all patients with measurable baseline disease had been followed to progression, or for 56 weeks. RESULTS: Fourteen patients received vandetanib. All patients experienced at least one adverse event (AE), and 7 patients (50%) experienced grade ≥3 AEs. Common AEs included diarrhea (79%), hypertension (64%), and rash (43%). Four patients reported a total of five serious AEs (SAEs). Eleven patients (79%) had dose interruptions, and 8 patients (57%) had dose reductions. One patient discontinued treatment because of an SAE (interstitial lung disease). No patients met the prespecified criterion for QTc prolongation. The ORR was 38% and PFS at 12 months was 85%. CONCLUSION: Safety and efficacy data were comparable to those previously reported, and AEs were generally manageable by standard clinical practice or dose modifications. Overall, vandetanib was considered to be beneficial for Japanese MTC patients. ABBREVIATIONS: AE = adverse event CI = confidence interval Css,max = maximum steady-state plasma concentration DCR = disease control rate EGFR = epidermal growth factor receptor ILD = interstitial lung disease MTC = medullary thyroid cancer ORR = objective response rate PFS = progression-free survival PK = pharmacokinetics RECIST = Response Evaluation Criteria in Solid Tumors RET = re-arranged during transfection SAE = serious adverse event VEGFR = vascular endothelial growth factor receptor.

Analysis of microbiota involved in the aged natural fermentation of indigo.

Although the indigo reduction process is performed via natural fermentation and maintained under open-air condition, the indigo-reducing reactions continue for 6 months (on average) or longer. Identifying the mechanism underlying the maintenance of this process could lead to the development of a novel, long-lasting, unsterilized bioprocesses. To determine the mechanisms underlying the maintenance of the indigo fermentation system microbiota for more than 6 months in a reduced state in an anaerobic alkaline environment, we examined changes in the microbiota in one early-phase batch and two aged batches of indigo fermentation fluid. The microbiota in the aged fermentation fluid consisted mainly of the genera Alkalibacterium, Amphibacillus, Anaerobacillus and Polygonibacillus and the family Proteinivoraceae. The genera Alkalibacterium, Amphibacillus and Polygonibacillus are known to include indigo-reducing bacteria. Although the transition speed was slower in the aged fermentation fluid than in the early-stage fluid, the microbiota in the aged fermentation fluid maintained for more than 6 months was drastically changed within a period of 3 months. The results of this study indicate that the bacterial consortia consisted of various indigo-reducing species that replace the previous group of indigo-reducing bacteria. The notable transitional changes may be concomitant with changes in the environmental conditions, such as the nutritional conditions, observed over 3 months. This flexibility may lead to important changes in the microbiota that allow for the maintenance of a fermentation-reducing state over a long period.

Polygonibacillus indicireducens gen. nov., sp. nov., an indigo-reducing and obligate alkaliphile isolated from indigo fermentation liquor for dyeing.

Obligately alkaliphilic and halophilic strains, designated In2-9T and D2-7, were isolated from a fermented Polygonum indigo (Polygonum tinctorium Lour.) liquor sample obtained from a craft centre in Date City, Hokkaido, Japan. The 16S rRNA gene sequence phylogeny suggested that strain In2-9T is a member of the genus Bacillus with the closest relatives being the alkaliphilic species of the genus Bacillus, Bacillus hemicellulosilyticusJCM 9152T (96.4 % 16S rRNA gene sequence similarity) and Bacillus alcalophilus DSM 485T (96.5 %). Cells of the isolate stained Gram-positive and were facultatively anaerobic straight rods that were motile by peritrichous flagella. Strain In2-9T grew between 13 and 45 °C with optimum growth at approximately 35-37 °C. The isolates grew in the pH range of 8-12 with optimum growth at pH 10. The isoprenoid quinone detected was menaquinone-6 (MK-6) and the DNA G+C content was 39.4 mol%. The whole-cell fatty acid profile mainly (>10 %) consisted of iso-C15 : 0, anteiso-C15 : 0 and C16 : 0. Spore shape and location and chemotaxonomic characteristics revealed that the isolates were distinctly different from phylogenetic neighbouring alkaliphilic species of the genus Bacillus. On the basis of phenotypic and chemotaxonomic characteristics and phylogenetic data, the isolates represent a novel species of a new genus, for which the name Polygonibacillusindicireducens gen. nov., sp. nov. is proposed. The type strain of the type species is In2-9T (=JCM 30831T=NCIMB 14982T), and strain D2-7 is an additional strain of the species.

The important risk factor for lateral pelvic lymph node metastasis of lower rectal cancer is node-positive status on magnetic resonance imaging: study of the Lymph Node Committee of Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: This study seeks to evaluate lateral pelvic lymph node (LPLN) and perirectal lymph node (PRLN) status on magnetic resonance imaging (MRI) as potential risk factors for lymph node metastasis. METHODS: The subjects were 394 patients with lower rectal cancer who underwent MRI prior to mesorectal excision (combined with lateral pelvic lymph node dissection in 272 patients) at 6 institutes. No patients received neoadjuvant therapy. Cases were classified as cN(+) and cN(-) based on the short axis of the largest lymph node ≥5 and <5 mm, respectively. LPLN and PRLN status and other clinicopathologic factors were analyzed by multivariate logistic regression. The importance of identified risk factors for lymph node metastasis was examined using the area under the curve (AUC). RESULTS: Independent risk factors for right LPLN metastasis included histopathological grade (G3 + G4), pPRLN(+), M1, cLPLN(+) [odds ratio (OR) 10.73, 95 % confidence interval (CI) 4.59-27.1], and those for left LPLN metastasis were age (<64), histopathological grade (G3 + G4), pPRLN(+), and cLPLN(+) (OR 24.53, 95 % CI 9.16-77.7). ORs for cLPLN(+) were highest. The AUCs for right and left cLPLN status of 0.7484 (95 % CI 0.6672-0.8153) and 0.7904 (95 % CI 0.7088-0.8538), respectively, were significantly higher than those for other risk factors. In contrast, the ORs for cPRLN(+) and cPRLN status of 2.46 (95 % CI 1.47-4.18) and 0.6396 (95 % CI 0.5917-0.6848) were not much higher than for other factors. CONCLUSIONS: An LPLN-positive status with a short axis ≥5 mm on MRI is an important predictor of LPLN metastasis, but PRLN status is not a strong predictor of PRLN metastasis.

Tyrosine-kinase inhibitors to treat radioiodine-refracted, metastatic, or recurred and progressive differentiated thyroid carcinoma [Review].

Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients' quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.

Low frequency of PAX8-PPARγ rearrangement in follicular thyroid carcinomas in Japanese patients.

Paired-box gene 8 (PAX8)-peroxisome proliferator-activated receptor-γ (PPARγ) gene fusion has been identified at significant frequency in follicular thyroid carcinomas (FTCs) with cytogenetically detectable translocation t(2;3)(q13;p25). This represents a possible specific molecular marker for follicular carcinoma. In this study, we examined PAX8-PPARγ rearrangement in 24 FTC samples from Japanese patients by reverse transcribed-polymerase chain reaction (RT-PCR) using two upstream PAX8 primers located in exons 7 and 8 and a downstream primer in exon 1 of PPARγ. The fusion gene was detected in only one of 24 FTCs (4%). The FTC with PAX8-PPARγ rearrangement from a 56-year-old man showed a product consistent with fusion between exon 8 of PAX8 and exon 1 of PPARγ. It was confirmed by direct sequencing. This FTC was histologically encapsulated, composed of trabeculae and small follicles and had complete penetration of the capsule by tumor tissues (minimally invasive type). The frequency of the fusion gene in this study was much lower than the 29-63% noted in reports from other countries suggesting that FTCs in Japanese patients may have a special genetic background, and that the high iodine intake from a typical Japanese diet might influence the frequency of the fusion gene in FTCs.

[Successful resection of a gastric aberrant pancreas causing gastrointestinal bleeding by laparoscopy and endoscopy cooperative surgery].

A man in his 50s was admitted to our hospital for treatment of hematemesis. Endoscopy revealed arterial bleeding from a gastric submucosal tumor and endoscopic hemostasis was successful. However, surgical resection was contemplated to prevent recurrent bleeding and for making a definitive diagnosis. Surgical resection was eventually performed by laparoscopy and endoscopy cooperative surgery (LECS), and the tumor was pathologically diagnosed to be a gastric aberrant pancreas. We think that LECS is suitable for a gastric aberrant pancreas causing gastrointestinal bleeding, because the procedure is effective for tumor resection with minimal removal of the stomach wall.