The Japanese Society of Thyroid Pathology and the Japan Association of Endocrine Surgeons developed the eighth edition of the General Rules for the Description of Thyroid Cancer (GRDTC) in December ...2019. This article describes the pathological diagnosis of the GRDTC, which has been improved through repeated revisions based on the experience of Japanese pathologists and translated into English to introduce the Japanese diagnostic standard to foreign countries. In this edition of the GRDTC, the histopathological classification and descriptions differ in some respects from those of the fourth edition of the World Health Organization (WHO) classification as revised in 2017. For example, the GRDTC does not adopt the concept of borderline lesions (FT-UMP, WDT-UMP, and NIFTP) of the WHO, taking into consideration the popular histological criteria accepted by Japanese pathologists. The cytological reporting system of the GRDTC was partly modified from the Bethesda system in 2015. It has an additional cyst fluid category separated from the unsatisfactory category that has been demonstrated to be useful in Japan. This translated edition makes it easy to submit Japanese clinicopathological studies of thyroid tumors in an international journal. We also wish to contribute to the improvement, standardization, and globalization of the pathological diagnosis of thyroid tumors.
The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in ...< 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1-73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.
Background
Total 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.
Methods
The 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 17.6 years. 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.
Results
The 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 25 years after surgery were 93.5, 90.6, and 93.6%, respectively. The cause-specific survival (CSS) rate at 25 years 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 45 years old or older, the group whose tumors were larger than 40 mm, and the group with extrathyroidal invasion. Based on the above findings, we classified the patients into four groups according to age <45 or ≥45 years, tumor size ≤40 or >40 mm, 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.
Conclusions
The 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 45 years, whose tumor diameter is 40 mm or less, and who do not have clinical lymph node metastasis or extrathyroidal invasion.
The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy ...with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication.
Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014).
Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication.
Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication.
KEY MESSAGES
Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication.
Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication.
Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.
Background
To safely perform minimized gastrectomy based on sentinel node (SN) concept for early gastric cancer patients, intraoperative diagnostic accuracy is indispensable. This study aimed to ...evaluate the clinical utility of the one-step nucleic acid amplification (OSNA) assay in the intraoperative diagnosis of SN metastasis in early gastric cancer patients compared with that of histopathological examination.
Methods
We conducted a prospective study using the OSNA assay for 43 patients with cT1N0M0 gastric cancer undergoing gastrectomy with SN mapping. All the SNs and selected non-SNs were examined by routine histopathological diagnosis, and the OSNA assay.
Results
We performed permanent histopathology (PH) in 1732 lymph nodes (LNs) (286 SNs and 1446 non-SNs) obtained from 43 patients. We also evaluated 439 LNs (286 SNs and 153 non-SNs) with the OSNA assay in addition to PH. Intraoperative histopathology (IH) was performed in 214 LNs (213 SNs and 1 non-SN). PH revealed LN metastasis in 6 patients (14%), all of whom showed positive SNs by PH. The diagnostic accuracy to predict the LN status based on the SN concept by histological examination was 100%. The concordance rate between the OSNA assay and the PH and IH were 0.970 and 0.981 respectively. Discordant results between PH and OSNA assay were observed in 13 LNs. The sensitivity and specificity of the OSNA assay compared with those of PH were 0.636, and 0.988, and compared with those of IH were 0.800, and 0.995.
Conclusion
Our results suggest that the OSNA assay is a useful and convenient tool for the intraoperative detection of SN metastasis in early gastric cancer patients.
The Japan Thyroid Association (JTA) recently published new guidelines for clinical management of thyroid nodules. This paper introduces their diagnostic system for reporting thyroid fine-needle ...aspiration cytology. There are two points where the new reporting system that differs from existing internationally-accepted ones. The first is the subclassification of the so-called indeterminate category, which is divided into ‘follicular neoplasm’ and ‘others’. The second is the subclassification of follicular neoplasm into ‘favor benign’, ‘borderline’ and ‘favor malignant’. It is characterized by self-explanatory terminologies as to histological type and probability of malignancy to establish further risk stratification as well as to facilitate communication between clinicians and cytopathologists. The different treatment strategies adopted for thyroid nodules is deeply influenced by the particular diagnostic system used for thyroid cytology. In Western countries all patients with follicular neoplasms are advised to have immediate diagnostic surgery while patients in Japan often undergo further risk stratification without immediate surgery. The JTA diagnostic system of reporting thyroid cytology is designed for further risk stratification of patients with indeterminate cytology. If a surgeon applies diagnostic lobectomy to all patients with follicular neoplasm unselectively, this subclassification of follicular neoplasm has no practical meaning and is unnecessary. Cytological risk stratification of follicular neoplasms is optional and cytopathologists can choose either a simple 6-tier system without stratification of follicular neoplasm or a complicated 8-tier system depending on their experience in thyroid cytology and clinical management.
Background
Recent advances in endoscopic examinations have resulted in the detection of a larger number of early esophageal cancers; however, there have been many cases with clinically negative but ...pathologically positive lymph node metastasis (LNM). In this study, we aimed to evaluate the discrepancy between the clinical and pathological diagnoses of LNM in patients with cT1a-MM/cT1b N0M0 esophageal cancer, and assess LNM size in these patients to clarify the presence of LNM that cannot be detected with current modalities.
Methods
This study included 50 patients who underwent surgery for cT1a-MM/cT1b N0M0 thoracic esophageal squamous cell carcinoma between January 2012 and November 2016 at our institution. The maximum size of involved LNs and metastatic nests were measured, and the distribution of LNM was investigated.
Results
Of the 50 patients, 13 (26%) had LNM on pathological examination. Lymphatic invasion was significantly more frequent in the LNM-positive group than in the LNM-negative group (
p
= 0.005). The median sizes of 28 involved LNs and metastatic nests were 3 and 1.6 mm, respectively. Of these LNs, 20 (71%) were classified as micrometastases (≤ 2 mm). The involved nodes were distributed across three fields.
Conclusions
There was a discrepancy between the clinical and final pathological findings of LNM in patients with cT1a-MM/cT1b N0M0 esophageal cancer. The detection of involved nodes with current modalities in these patients was difficult because of the small size of LNM. Therefore, continued strong consideration for extended LN dissection is necessary in these patients to ensure appropriate diagnosis and treatment.
The aim of this study was to assess a three-dimensional (3D) correlation between preoperative 3D bone single photon emission CT (SPECT)/CT, which allows the visualization of radiotracer uptake on 3D ...volume-rendered CT images, and histopathological characteristics in the medication-related osteonecrosis of the jaw (MRONJ).
We conducted a full histopathological assessment of the resected jaws in four patients with Stage 2 or 3 MRONJ. The pathologic results were classified as follows: necrosis without any tissue vascularity (
+ V-), necrosis with both vascularity and acute inflammatory cell infiltration due to bacterial infection (
+ V+I+), necrosis with regenerative vasculature but no inflammatory cell infiltration (
+ V+I-), and chronic inflammation without massive necrosis (N-V +I+). These classifications were correlated with imaging results.
The
+ V- areas visually represented the area of necrotic bone exposed to the oral cavity and were consistent with defect area of radioisotope uptake in SPECT/CT. The
+ V- areas were surrounded by the
+ V+
+ areas where increased radiotracer uptake was clearly seen. Also, abnormal uptake was found in both of the
+ V+I- and N-V +I+ areas. The extensive surgical resections from necrotic core to bloody viable margins were performed in all cases, although one had the recurrence of MRONJ at the margin showing abnormal uptake that histologically represented the
+ V+I- area.
Radiologic-pathologic correlation of MRONJ could be achieved using 3D SPECT/CT. The presence of regenerative vascularity with necrosis or inflammation seemed to determine bone metabolism in MRONJ. The recurrence of MRONJ was observed in one case, and 3D SPECT/CT had preoperatively depicted the recurrence site.
The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid ...culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid–like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.
•We developed a culture system for murine thyroid organoids.•TSH stimulated thyroid organoid formation and growth.•TSH-responsive thyroid organoids formed functional thyroid-like tissue in vivo.•NRASQ61R-positive, p53−/− organoids gave rise to thyroid cancer.
Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. Here we report a retrospective study of the treatment and other factors associated with its outcomes.
The ...medical records of 100 patients diagnosed with ATC at Ito Hospital between 1993 and 2009 were reviewed and pertinent information was extracted and analyzed.
There were 80 women and 20 men, and their median age at diagnosis was 68 years (range, 41-90 years). Thirteen patients had a history of well-differentiated thyroid carcinoma. Six patients had a small ATC focus within a differentiated carcinoma. All cases were retrospectively staged according to the Union for International Cancer Control classification system, and the results were stage IVA in 11 cases, stage IVB in 31 cases, and stage IVC in 58 cases. Seventy patients underwent surgical treatment, and complete resection was performed in 24 of them. Seventy-eight patients received radiotherapy, and 58 of them received a total dose of ≥40 Gy. Twenty-seven patients received chemotherapy. Only 15 patients received multimodal therapy (surgery, radiotherapy, and chemotherapy). The 1-year survival rates according to stage were as follows: stage IVA, 72.7%; stage IVB, 24.8%; and stage IVC, 8.2%. Multivariate analysis identified age ≥70 years, white blood cell ≥10,000 mm(3), extrathyroidal invasion, and distant metastasis at the time of diagnosis as prognostic factors. Survival after complete resection was significantly better than after incomplete resection or no resection. The results also suggested that radiation doses of ≥40 Gy were associated with significantly longer survival.
Although the prognosis of most patients with ATC continues to be poor, surgery, radiotherapy, and a combination of both improved the survival of patients with ATC.
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