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.

Radiological predictive factors on preoperative multimodality imaging are related to Oncotype DX recurrence score in estrogen-positive/human epidermal growth factor receptor 2-negative invasive breast cancer: a cross-sectional study.

OBJECTIVE: The Oncotype DX (ODX) estimates the 10-year risk of metastasis or recurrence of breast cancer and indicates whether chemotherapy is likely to be effective; however, the high cost of this test may limit its use for patients. The aim of this study was to evaluate the potential of preoperative imaging using mammography (MMG), ultrasonography (US), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and positron emission tomography/computed tomography (PET/CT) metabolic parameters in predicting the ODX recurrence score (ODXRS), which prognosticates estrogen receptor-positive (ER +)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. METHODS: This retrospective study was conducted on 51 patients with ER+/ HER2- early-stage breast cancer with preoperative images available. Surgical specimens were sent for ODX assay and the ODXRS was categorized as low (<18) or intermediate/high (≥18). MMG/US findings were classified according to BI-RADS categories. For MRI analysis, tumor growth orientation was evaluated in addition to morphological assessment in BI-RADS. For PET/CT analysis, standardized uptake value (SUV) of the tumor were measured. Patient, tumor, and image characteristics were compared between the two groups, and predictors of the low ODXRS group were determined by logistic regression analysis. Two-sided P values less than 0.05 were considered statistically significant. RESULTS: Thirty-two (63%) and 19 (37%) patients were categorized as low and intermediate/high ODXRS, respectively. On univariate analysis, nuclear grade, tumor margin, and tumor growth orientation on MRI, and SUVmax on PET/CT were significantly associated with a low ODXRS. Multivariate analysis revealed that tumor growth orientation perpendicular to the Cooper's ligament on MRI (P = 0.031) and a low SUVmax on PET/CT (P = 0.016) were independent prognostic factors for a low ODXRS. As a predictor of low ODXRS, the receiver operating characteristic (ROC) analysis of the SUVmax showed that using 3.0 as the optimal cut-off value has a sensitivity and specificity of 94.4% and 73.0%, respectively, with an area under the curve (AUC) of 0.923. CONCLUSIONS: The combination of perpendicular tumor growth orientation to Cooper's ligaments on MRI and a low SUVmax on PET/CT may predict a low ODXRS.

Predictive value of metastatic lateral lymph node ratio for recurrence in pathologically lateral lymph node-positive papillary thyroid cancer patients with palpable lymph nodes.

BACKGROUND: This study aimed to identify the predictive value of the extent of metastatic lymph nodes in the central and lateral neck compartment for recurrence in papillary thyroid cancer (PTC) patients with pathologically lateral lymph node metastasis (pN1b). METHODS: This study enrolled 252 patients with pN1b from PTC. RESULTS: During a mean follow-up of 17.6 years, 55 (21.8%) patients experienced recurrence. Patients with palpable lymph nodes were more likely to have a recurrence than those with nonpalpable lymph nodes (30.1% vs. 17.8%, relative risk 1.7, 95%CI: 1.1-2.7). For patients with palpable metastatic lymph nodes, lymph node ratio of lateral lymph nodes ≥0.5 (aHR = 2.906, 95%CI: 1.29-6.54) and age ≥55 years (aHR = 2.508, 95%CI: 1.12-5.63) were independent prognostic factors. For those without palpable nodes, age ≥55 years (aHR = 2.224, 95%CI: 1.08-4.60) and tumor size >4 cm (aHR = 2.168, 95%CI: 1.01-4.66) were independently predictive of worse RFS. CONCLUSIONS: Palpable lymph nodes were approximately twice as likely to recur as nonpalpable nodes. Metastatic lateral lymph node ratio predicts recurrence in pN1b PTC patients with palpable lymph nodes, but not those without ones.

Ovarian metastasis from breast cancer mimicking a primary ovarian neoplasm: A case report.

Ovarian metastasis (OM) from breast cancer accounts for 3-38% of all ovarian neoplasms and is associated with various characteristic clinical presentations, such as pseudo-Meigs syndrome and Krukenberg tumor. Accurate diagnosis of OM may be challenging, as such lesions are frequently asymptomatic until they reach a large size. Occasionally, metastatic ovarian cancer is detected prior to the diagnosis of the primary tumor. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extraovarian tumor metastases and may be helpful for identifying the primary tumor site. We herein report a case of OM from breast cancer masquerading as primary ovarian cancer. However, the correct diagnosis was made based on histopathological and immunohistochemical examinations. The patient had bilateral breast cancer, namely invasive lobular carcinoma of the left breast and ductal carcinoma of the right breast. Due to the presence of bilateral synchronous breast tumors, the possibility that the patient had hereditary breast and ovarian cancer syndrome or other relevant genetic factors was considered. Immunohistochemistry plays a key role in distinguishing between primary ovarian tumors and OM, and it was also important for confirming the metastatic nature of the ovarian lesion and diagnosing the primary tumor in the present study.

Time-Varying Pattern of Mortality and Recurrence from Papillary Thyroid Cancer: Lessons from a Long-Term Follow-Up.

Background: Little is known about annual hazard rates of cancer mortality and recurrence for papillary thyroid cancer (PTC). This study investigated the time-varying pattern of cancer death and recurrence from PTC and independent prognostic factors for cause-specific mortality (CSM) and recurrence of PTC. Methods: This retrospective chart review enrolled 466 patients diagnosed with PTC who underwent curative initial surgery between April 1981 and December 1991 with a median follow-up of 18.4 years. Clinical characteristics, cancer mortality (primary endpoint), and recurrence (secondary endpoint) were ascertained. The failure rates of either death or recurrence were estimated using the Kaplan-Meier methods, and annual death/recurrence hazard was depicted using hazard function. Results: In this Japanese cohort where only 1.5% of patients received radioactive iodine therapy, the 10-, 20-, and 30-year CSM rates were 2.7%, 6.2%, and 8.6%, respectively. Eleven (44.0%) cases of death occurred within the first 10 years, whereas 10 (40.0%) and 4 (16.0%) cases occurred within 10-20 and 20-30 years after surgery, respectively. The 10-, 20-, and 30-year recurrence rates were 11.3%, 21.8%, and 29.4%, respectively. Forty-six (54.8%) cases of recurrence occurred within the first 10 years, predominantly within the first five years (31 cases; 36.9%), whereas 29 (34.5%), 7 (8.3%), and 2 (2.4%) cases occurred within 10-20, 20-30, and ≥30 years after surgery, respectively. Age ≥55 years was the only independent prognostic factor for CSM. Age ≥55 years, male, tumor size > 4 cm, extranodal extension, and positive pathological lymph node metastasis were independent prognostic factors for recurrence. The annual hazard curve of cancer mortality presented a double-peaked distribution, with a first peak at the 10th year, and the second peak reaching the maximum at the 20th year after surgery for the entire population. The annual hazard curve of recurrence showed a triple-peaked pattern, with surges at about 12, 22, and 29 years after surgery. Conclusions: Patients with PTC harboring at least one of the prognostic characteristics may be at persistent risk of cancer mortality and recurrence even 10 or more years after initial treatment. Understanding the hazard rate of PTC is key to creating more tailored treatment and surveillance.

Synchronous and bilateral oncocytic carcinoma of the breast: A case report and review of the literature.

Synchronous bilateral breast cancer is rare, and oncocytic carcinoma is an even rarer breast cancer histological subtype. In general, oncocytic tumors are defined as neoplasms with eosinophilic granular cytoplasm and have been reported in various organs. Oncocytic carcinoma of the breast was first documented by Gadaleanu and Craciun in 1987, and 48 cases have since been reported. The present study reports a case of synchronous bilateral breast oncocytic carcinoma. The patient was a 78-year-old woman. Although she exhibited no symptoms, chest computed tomography revealed three multinodular breast tumors: Two in the right breast and one in the left. Core needle biopsy was performed on the three tumors, and the patient was diagnosed with invasive ductal carcinoma with potential apocrine carcinoma. A bilateral modified radical mastectomy was performed. Surgical specimens of the three tumors revealed cord- or nest-forming tumor cells with eosinophilic granular cytoplasm. Immunohistochemically, the tumor cells were markedly positive for mitochondria. Electron microscopy of the tumor samples additionally revealed numerous mitochondria filling the cytoplasm. Based on these findings, the tumors were diagnosed as oncocytic carcinoma. The pathogenesis of oncocytic carcinoma remains to be fully elucidated; thus, additional clinicopathological studies are required.

Radiation recall dermatitis occurring 6 years and 4 months after breast-conserving surgery: A case report.

Currently in Japan, breast-conserving therapy, consisting of breast-conserving surgery and post-operative radiation therapy, is performed frequently for the treatment of invasive breast cancer. It has been demonstrated that radiation therapy not only prevents recurrence in the preserved breast, but that it also contributes to improved patient survival. The present study describes the case of a 37-year-old woman with radiation recall dermatitis that occurred 6 years and 4 months after breast-conserving surgery. Erythema with a relatively distinct border was observed at the irradiated site on the left breast; eczema was diagnosed by a dermatologist. Inflammatory breast cancer was ruled out, since chest X-ray, abdominal ultrasound and bone scintigraphy were negative. Following ~1 month of topical corticosteroid application and oral second generation antihistamine treatment, the erythema was alleviated and the subjective symptoms also disappeared. Only a few cases of radiation recall dermatitis have been described in the fields of radiology and dermatology, but not yet in the surgical field. In the future, the incidence of radiation recall dermatitis is predicted to increase due to the increasing number of patients undergoing breast-conserving therapy. Whether in the surgical, radiological or dermatological field, if erythema is detected at the irradiated site during post-operative follow-up, routine care should be provided, keeping in mind the possibility of radiation recall dermatitis and inflammatory breast cancer.

Clinical significance of hepatocyte growth factor/c-Met expression in the assessment of gastric cancer progression.

Among the mechanisms that control cancer progression, cell mobility is a significant factor required for cellular liberation from the primary focus and infiltration. Hepatocyte growth factor (HGF) has been shown to facilitate cell mobility. In the present study, the clinical significance of the HGF/c­Met pathway in the assessment of gastric cancer progression was evaluated. From a cohort of patients with gastric cancer who underwent surgical resection between April 1999 and March 2003, 110 subjects were randomly selected. Preoperative serum HGF levels were measured and various pathological factors were analyzed. Furthermore, 50 subjects were randomly selected from within this group and immunohistochemical staining of tissue preparations for HGF and its receptor c­Met were performed. In the infiltrative growth pattern [(INF)α,ß vs. INFγ], advanced progression was associated with elevated preoperative serum HGF levels (P<0.001). No correlation was identified between serum HGF levels and immunostaining for HGF or c­Met in the tissue preparations. Immunostaining revealed a significant correlation between c­Met expression and lymphatic vessel invasion (ly0.1 vs. 2.3; P=0.0416), lymph node metastasis (n0.1 vs. 2; P=0.0184) and maximum tumor diameter (≤50 mm vs. >50 mm; P=0.0469). Furthermore, c­Met­positivity was associated with a significant difference in overall survival (P=0.0342), despite stage I and II cases accounting for 82% of the total cohort (41 of 50 cases). These results suggested that the expression of the HGF/c­Met pathway in gastric cancer may be a potential predictive factor for disease progression.

Efficacy of lapatinib monotherapy on occult breast cancer presenting with cutaneous metastases: A case report.

The case of a 72-year-old female who identified a lymph node enlargement in the left axilla is reported in the present study. A lymph node biopsy revealed a metastatic adenocarcinoma of the axillary lymph node. Following various assessments, the patient was diagnosed with occult breast cancer and lymph node metastases, for which treatment was initiated. Trastuzumab monotherapy was administered as the patient was elderly, positive for the hepatitis B virus and exhibited the following immunostaining/immunohistochemical analysis results: Estrogen receptor (ER) negative (-), progesterone receptor (PgR) negative (-) and human epidermal growth factor receptor 2 (HER2) positive (3+). Breast ultrasonography was performed 10 months after the initial trastuzumab administration and the left axillary lymph node enlargement had reduced in size and severity. However, a skin rash (erythema) was observed encompassing the left breast and extending into the axilla. As determined by the result of a skin biopsy of this area, the patient was diagnosed with occult breast cancer with cutaneous metastases. The immunohistochemical analysis results obtained from the skin biopsy were similar to those obtained from the lymph nodes: ER (-), PgR (-) and HER2 (3+). Therefore, the patient was switched from trastuzumab to lapatinib monotherapy. The erythema completely disappeared after two months of treatment. At present (34 months following lapatinib monotherapy initiation) no new lesions or severe side-effects have been observed.

A Crohn's disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1.

A common mutation in the gene encoding the cytoplasmic sensor Nod2, involving a frameshift insertion at nucleotide 3020 (3020insC), is strongly associated with Crohn's disease. How 3020insC contributes to this disease is a controversial issue. Clinical studies have identified defective production of interleukin 10 (IL-10) in patients with Crohn's disease who bear the 3020insC mutation, which suggests that 3020insC may be a loss-of-function mutation. However, here we found that 3020insC Nod2 mutant protein actively inhibited IL10 transcription. The 3020insC Nod2 mutant suppressed IL10 transcription by blocking phosphorylation of the nuclear ribonucleoprotein hnRNP-A1 via the mitogen-activated protein kinase p38. We confirmed impairment in phosphorylation of hnRNP-A1 and binding of hnRNP-A1 to the IL10 locus in peripheral blood mononuclear cells from patients with Crohn's disease who bear the 3020insC mutation and have lower production of IL-10.