CA19-9 producing locally advanced papillary thyroid carcinoma: a case report.

BACKGROUND: CA19-9 is a tumor marker for gastrointestinal and biliary-pancreatic adenocarcinomas; however, its association with thyroid cancer is unknown. Here, we report a case of CA19-9 producing locally advanced papillary thyroid carcinoma (PTC). CASE PRESENTATION: A 66-year-old woman who was identified with a thyroid tumor after a close examination of an elevated serum CA19-9 level, which was detected at health screening, was referred to our hospital. Ultrasonography revealed a 34 × 31 mm hypoechoic lesion in the lower pole of the left thyroid lobe. Computed tomography revealed a solid thyroid tumor with tracheal invasion without any distant metastases. Bronchoscopy revealed tumor exposure into the tracheal lumen on the left side of the trachea. Fine-needle aspiration cytology led to a diagnosis of papillary thyroid carcinoma (PTC). The patient underwent a total thyroidectomy, tracheal sleeve resection with end-to-end anastomosis, and lymph node dissection in the left cervical and superior mediastinal regions (D3c) with a reversed T-shaped upper sternotomy down to the third intercostal level. Histopathological analysis confirmed the diagnosis of PTC with tracheal invasion and no lymph node metastases (pT4a Ex2 N0). Immunohistochemical staining showed the expression of CA19-9 in cancer cells. Postoperatively, the serum CA19-9 level of the patient decreased to within the normal range. CONCLUSIONS: Some PTCs produce CA19-9, although less frequently. When elevated serum CA19-9 levels are observed, PTC should be included in the differential diagnosis for further investigation.

Eribulin promotes proliferation of CD8+ T cells and potentiates T cell-mediated anti-tumor activity against triple-negative breast cancer cells.

PURPOSE: Chemotherapeutic agents exert immunomodulatory effects on triple-negative breast cancer (TNBC) cells and immune cells. Eribulin favorably affects the immunological status of patients with breast cancer. However, the effects of eribulin on the immune cells remain unexplored. The aim of this study was to investigate the effects of eribulin on immune cells. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and mouse splenocytes were stimulated with anti-CD3 and anti-CD28 antibodies. The effects of eribulin and paclitaxel on cell proliferation and differentiation status were analyzed using flow cytometry. RNA sequencing was performed to assess alterations in gene expression in CD8+ T cells following eribulin and paclitaxel treatment. Using TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157), the anti-tumor activity of CD3/CD28-stimulated T cells combined with eribulin or paclitaxel was evaluated. RESULTS: Eribulin did not affect CD3/CD28-stimulated PBMCs proliferation. However, eribulin significantly decreased the CD4/CD8 ratio in T cells, indicating that eribulin facilitates CD8+ T cell proliferation. Furthermore, eribulin significantly increased the frequency of less differentiated CD45RA+, CCR7+, and TCF1+ subsets of CD8+ T cells. RNA sequencing revealed that eribulin enhanced the expression of gene sets related to cell proliferation and immune responses. Moreover, eribulin augmented the anti-tumor effects of CD3/CD28-stimulated T cells against TNBC cells. These results were not observed in experiments using paclitaxel. CONCLUSIONS: Eribulin promoted CD8+ T cell proliferation, repressed effector T cell differentiation, and harnessed T cell-mediated anti-tumor effects. These mechanisms may be one of the cues that eribulin can improve the immunological status of tumor-bearing hosts.

Development of a predictive score for post-hemithyroidectomy hypothyroidism using skeletal muscle index, remnant thyroid index, and thyroid-stimulating hormone levels: a retrospective cohort study.

Background: Hypothyroidism is a major complication of hemithyroidectomy. Low remnant thyroid volume and high serum thyroid-stimulating hormone (TSH) levels are suggested as risk factors for post-hemithyroidectomy hypothyroidism. Reduced skeletal muscle mass is associated with a variety of postoperative complications. However, its impact on post-hemithyroidectomy hypothyroidism has not yet been studied. This study aimed to evaluate the association between skeletal muscle mass and the onset of post-hemithyroidectomy hypothyroidism and develop a predictive score using skeletal muscle mass in combination with previously reported risk factors. Methods: This study retrospectively analyzed 226 consecutive patients who underwent hemithyroidectomy at Shinshu University Hospital between January 2011 and December 2020. The skeletal muscle area at the fourth thoracic vertebral level and maximal remnant thyroid area were quantified using preoperative computed tomography and standardized by dividing them by the square of the patient's height, designated as the skeletal muscle index (SMI) and remnant thyroid volume index (RTI). Subclinical hypothyroidism was defined as a postoperative elevated serum TSH level (>5 µU/mL) with a normal free thyroxine (FT4) level (≥0.9 ng/dL), overt hypothyroidism as a postoperative increase in serum TSH level (>5 µU/mL) and a decrease in serum FT4 level (<0.9 ng/dL), and symptomatic hypothyroidism as an elevated serum TSH level (>5 µU/mL) with hypothyroidism-related symptoms. Logistic regression analysis was used to determine the factors associated with the onset of hypothyroidism. Results: Patients with euthyroid status had significantly higher SMI and RTI than those who developed post-hemithyroidectomy hypothyroidism (SMI, euthyroid: 12.0±2.4 vs. subclinical hypothyroid: 10.2±1.7, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 10.1±1.7, P<0.001, RTI, euthyroid: 1.19±0.41 vs. subclinical hypothyroid: 0.92±0.35, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 0.84±0.30, P<0.001). Multivariable analysis demonstrated that low SMI, low RTI [hazard ratio (HR): 3.35, P<0.001], and preoperative high serum TSH levels (HR: 2.54, P=0.003) were independent predictive factors for hypothyroidism. Patients who had low SMI, low RTI, and preoperative high serum TSH levels were more likely to develop hypothyroidism (68.8%) than those with either one (25.3%), two (47.8%), or none (15.2%) of these three factors. Conclusions: Preoperative evaluation of the SMI, RTI, and serum TSH levels may be useful in predicting the development of post-hemithyroidectomy hypothyroidism.

Significance of skeletal muscle index-to-body mass index ratio as a predictor of post-surgical bleeding after mastectomy in patients with breast cancer.

BACKGROUND: Post-surgical bleeding is a major complication of mastectomy in patients with breast cancer. However, the risk factors for post-surgical bleeding have not been well studied. Although obesity or reduced skeletal muscle mass is an indicator of cancer surgery complications, its impact on post-surgical bleeding after mastectomy remains unknown. METHODS: In total, 563 patients with breast cancer who underwent mastectomy were included in this study. We evaluated the preoperative body mass index (BMI), skeletal muscle index (SMI), and SMI-to-BMI ratio and analyzed the association between these values and the incidence of post-surgical bleeding. RESULTS: Post-surgical bleeding occurred in 33 (5.6%) patients. Mean BMI was significantly higher in the bleeding group (26.3 ± 4.7) than in the no-bleeding group (23.0 ± 4.1) (p < 0.001), whereas mean SMI was lower in the former group (45.0 ± 8.5) than in the latter group (48.0 ± 8.5) (p = 0.08). The bleeding group had significantly lower SMI-to-BMI ratio (1.71 ± 0.16) than the no-bleeding group (2.10 ± 0.23) (p < 0.001). Among these three parameters, SMI-to-BMI ratio had the highest area under the curve value in their receiver operating characteristic curves (0.73 for BMI, 0.59 for SMI, 0.92 for SMI-to-BMI ratio). Furthermore, on multivariate analysis, SMI-to-BMI ratio was an independent risk factor for post-surgical bleeding (hazard ratio, 38.4; 95% confidence interval, 13.9-136.2; p < 0.001). CONCLUSIONS: SMI-to-BMI ratio is a superior predictive factor of post-surgical bleeding after mastectomy to either BMI or SMI alone.

Neutrophil-to-Lymphocyte Ratio Is Associated With the Proportion of Poorly Differentiated Components in Papillary Thyroid Carcinoma.

INTRODUCTION: Diagnosis of poorly differentiated thyroid cancer (PDTC) requires ≥ 50% of poorly differentiated components (PDC) in Japan. However, the optimal cutoff percentage of PDC for PDTC diagnosis remains controversial. Although high neutrophil-to-lymphocyte ratio (NLR) correlates with the aggressiveness of papillary thyroid cancer (PTC), whether NLR is associated with the proportion of PDC in PTC remains unstudied. MATERIALS AND METHODS: Patients with the pure PTC (n = 664), PTC with < 50% PDC (n = 19), or PTC with ≥ 50% PDC (n = 26) who underwent surgery were retrospectively analyzed. Twelve-year disease-specific survival and preoperative NLR were compared among these groups. RESULTS: Twenty seven patients died from thyroid cancer. The PTC with ≥ 50% PDC group (80.7%) showed significantly worse 12-year disease-specific survival than the pure PTC group (97.2%) (P < 0.001); however, the < 50% PDC group (94.7%) did not (P = 0.91). The PTC with ≥ 50% PDC group had a significantly higher NLR than the pure PTC (P < 0.001) and the PTC with < 50% PDC groups (P < 0.001), whereas there was no significant difference in the NLR between the pure PTC and the PTC with < 50% PDC groups (P = 0.48). CONCLUSIONS: PTC with ≥ 50% PDC is more aggressive than either pure PTC or PTC with < 50% PDC, and NLR potentially reflects the PDC proportion. These results support the validity of 50% PDC as a cut-off for PDTC diagnosis and indicate the utility of NLR as a biomarker for PDC proportion.

Changes in the pathophysiology of primary hyperparathyroidism and analysis of postoperative recurrence cases at a regional core hospital in Japan: experience of 35 years in Shinshu University Hospital.

BACKGROUND: Since reoperation for recurrent primary hyperparathyroidism (PHPT) increases the risk of complications, such as recurrent laryngeal nerve palsy, it is vital to prevent recurrence as much as possible when performing the initial surgery. Therefore, we retrospectively analyzed the PHPT cases at Shinshu University Hospital from 1986 to 2020 for changes in the characteristics of PHPT over time and features of the recurrent cases to establish treatment strategies to prevent a postoperative recurrence. METHODS: Hereditary PHPT was diagnosed through endocrinological tests, systemic imaging, and/or genetic testing. Localization of swollen parathyroid glands was identified through neck ultrasonography (US), contrast-enhanced computed tomography, magnetic resonance imaging (MRI), and 99mTc-sestamibi scintigraphy. RESULTS: Among the 536 patients with PHPT (374 women and 162 men) with a mean age of 56.9±13.6 years, 90 (16.8%) had hereditary PHPT, while the other 446 (83.2%) had sporadic PHPT. Overall, 314 (58.6%) patients were asymptomatic, whereas 132 (24.6%) had symptoms related to PHPT. Asymptomatic PHPT was significantly more prevalent after 2001 (81.8%) than before 2001 (51.2%) (P<0.01), although the number of PHPT cases increased during the last decade. Resection of an enlarged parathyroid gland alone was performed for sporadic PHPT, while focused parathyroidectomy was performed after 2001. Total parathyroidectomy (TPTx) with autotransplantation was performed in patients with hereditary PHPT. In addition, the intraoperative rapid pathological diagnosis of the resected gland throughout the period and intraoperative serum intact parathyroid hormone (PTH) measurement from 2014 were used. Overall, 11 patients with hereditary PHPT (2.1%) developed recurrence. A recurrent parathyroid gland was identified in 10 of 11 cases through 99mTc-sestamibi scintigraphy. CONCLUSIONS: Although the incidence of asymptomatic PHPT has been increasing recently, focused parathyroidectomy is considered an appropriate procedure for sporadic PHPT that has been carefully examined preoperatively. Therefore, in the future, it will be necessary to conduct genetic testing for sporadic PHPT cases as much as possible to accurately diagnose the disease type and decide on a treatment strategy.

The Advantage of Using an Optical See-Through Head-Mounted Display in Ultrasonography-Guided Needle Biopsy Procedures: A Prospective Randomized Study.

An optical see-through head-mounted display (OST-HMD) can potentially improve the safety and accuracy of ultrasonography (US)-guided fine-needle aspiration. We aimed to evaluate the usefulness of an OST-HMD in US-guided needle-puncture procedures. We conducted a prospective randomized controlled study in which we compared the accuracy and safety of the US-guided needle puncture procedure and the stress on the practitioner when using OST-HMD versus standard US display (SUD). Inexperienced medical students were enrolled and randomly divided into two groups. A breast phantom was used to evaluate the required time and accuracy of the US-guided needle puncture. Practitioner stress was quantified using a visual analog scale (VAS). When the procedure was performed for the first time, the time required to reach the target lesion at a shallow depth was significantly shorter in the OST-HMD group (39.8 ± 39.9 s) than in the SUD group (71.0 ± 81.0 s) (p = 0.01). Using the OST-HMD significantly reduced the unintentional puncture of a non-target lesion (p = 0.01). Furthermore, the stress felt by the practitioners when capturing the image of the target lesion (p < 0.001), inserting and advancing the needle more deeply (p < 0.001), and puncturing the target lesion (p < 0.001) was significantly reduced in the OST-HMD group compared with that in the SUD group. Use of OST-HMD may improve the accuracy and safety of US-guided needle puncture procedures and may reduce practitioner stress during the procedure.

Surgical resection of the primary tumor prevents an undesirable locoregional condition and improves the quality of life in patients with anaplastic thyroid cancer.

PURPOSE: Anaplastic thyroid cancer (ATC) is a highly aggressive tumor that invades surrounding tissues and rapidly metastasizes throughout the body. Growth of the primary tumor in the neck often causes serious conditions that decrease the quality of life (QOL) of patients. The objective of this study was to investigate the role of surgical resection in improving the QOL of patients with ATC. METHODS: This was a retrospective review of 62 patients with ATC treated at Shinshu University Hospital between January 2001 and June 2019. RESULTS: Fourteen patients underwent R0/R1 resection. Thirteen of the 14 patients received postoperative radiation, and 4 received chemotherapy. The mean survival period was 15.4 ± 18.2 (range, 2-75) months. Distant metastases appeared within 3.2 ± 2.3 months postoperatively in 12 patients. A permanent tracheostomy was required in six patients; however, eight patients did not show airway obstruction until death. Daily treatment for exudate or bleeding from tumors that eroded in the neck, which deteriorated the QOL, was unnecessary in 12 patients. CONCLUSIONS: As surgical resection can improve the QOL in patients with ATC, thyroid surgeons should promptly and carefully evaluate the resectability of the tumor and favor resection as much as possible.

Skeletal muscle loss during neoadjuvant chemotherapy predicts poor prognosis in patients with breast cancer.

BACKGROUND: The skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level divided by height squared, has been considered a prognostic factor in patients with breast cancer. However, the prognostic impact of changes in SMI during treatment remains unclear. This study aimed to evaluate the influence of SMI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). METHODS: We reviewed patients with breast cancer who underwent NAC and subsequent surgery for breast cancer between 2010 and 2017. The rate of SMI change during NAC was calculated, and the association between SMI changes and prognosis was retrospectively analyzed. RESULTS: In total, 141 patients were evaluated. 48 (34.0%), 53 (37.6%), and 40 (28.4%) patients exhibited increased (≥ 3%), maintained (- 3% <, < 3%), and decreased (- 3% ≥) SMI during NAC, respectively. The decreased SMI group showed significantly poorer disease-free survival than the maintained and increased SMI groups (hazard ratio [HR] 8.29, p <  0.001 for the decreased vs. increased SMI groups; HR 3.49, p <  0.001 for the decreased vs. maintained SMI groups). Moreover, decreased SMI was an independent risk factor for disease-free survival in multivariate analysis (HR 3.68, p <  0.01). CONCLUSIONS: Skeletal muscle loss during NAC predicts poor prognosis. Our results underscore the importance of monitoring and maintaining skeletal muscle mass during NAC.

Fibroadenoma in a young male breast: A case report and review of the literature.

Fibroadenomas are the most common benign breast tumors in women, but rarely occur in men. Herein, we present a case of fibroadenoma occurring in a young, healthy male without hormonal alterations. This indicates that fibroadenoma should be regarded as differential diagnosis for tumors in the male breast.

Prognostic significance of neutrophil-to-lymphocyte ratio for long-term outcomes in patients with poorly differentiated thyroid cancer.

Poorly differentiated thyroid cancer (PDTC) is a distinct but rare type of thyroid cancer with intermediate biological behavior between differentiated and anaplastic thyroid cancers. PDTC was first defined in 2005 in Japan, but the diagnostic criteria changed in 2015, requiring the tumor to have more than 50% of poorly differentiated components for diagnosis. Because only six years have passed since the PDTC definition change, prognostic factors for long-term survival who meet the latest criteria have not been determined. Neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in various solid malignancies. However, its impact on PDTC remains unclear. This study aimed to evaluate the significance of NLR as a prognostic factor for patients with PDTC diagnosed based on the latest criteria. In total, 28 PDTC cases (4.4%) of 637 thyroid cancer patients who underwent surgery between 2002 and 2012 were retrospectively analyzed. The median follow-up period was 120 months (range, 7-216 months). Of the 13 deaths (46.4%), 9 patients (32.1%) died from PDTC. The median preoperative NLR was 2.7 (0.67-8.62), and the NLR cut-off value determined by the receiver operating characteristic curve was 2.88. Patients with a high NLR (>2.88) showed significantly worse disease-specific survival (hazard ratio [HR] 4.67, p = 0.036) and overall survival (HR 4.94, p = 0.007) than those with a low NLR (≤2.88). Multivariate analysis revealed that a high NLR independently predicted a worse prognosis (HR 6.06, p = 0.0087). In conclusion, NLR is a useful prognostic marker for patients with PDTC.

Papillary thyroid microcarcinoma with lung metastases: a case report and review of the literature.

BACKGROUND: Distant metastasis from papillary thyroid microcarcinoma (PTMC) is rare. Here we report a case of PTMC with multiple lung metastases. CASE PRESENTATION: A 64-year-old man presented to our hospital with abdominal pain. Computed tomography incidentally revealed multiple lung nodules. The lung tumor was histologically diagnosed as metastasis of papillary thyroid carcinoma (PTC) by core needle biopsy via thoracoscopy. The patient was referred to our department for further examination. Neck ultrasonography revealed a 0.9 cm hypoechoic nodule in the right lobe of the thyroid gland, which was diagnosed as PTC by fine-needle aspiration cytology. Subsequently, total thyroidectomy was performed, followed by radioiodine therapy. Iodine-131 (131-I) scintigraphy showed a strong accumulation in the lung metastasis. The patient presented no evidence of progression of lung metastasis for 25 months after the operation. CONCLUSIONS: Lymph node metastasis or extraglandular extension has been reported in the few published cases of metastatic PTMC, including the present case, and the average age of these cases was 58.8 ± 12.0 years. Although active surveillance without surgical resection is expected to become a standard of care for PTMC, this case indicates that a subset of PTMC patients with risk factors may develop distant metastases. Hence, careful preoperative screening is required to avoid complications associated with completion thyroidectomy.

Comparative efficacy and safety of tyrosine kinase inhibitors for thyroid cancer: a systematic review and meta-analysis.

The tyrosine kinase inhibitors (TKIs) sorafenib, lenvatinib, vandetanib, and cabozantinib are currently used for thyroid cancer treatment; however, the differences in their clinical efficacy and toxicity remain unclear. This meta-analysis assessed the efficacy and toxicity of these four TKIs based on 34 studies. The pooled incidence of partial response (PR), stable disease (SD), TKI-related adverse events (AEs), and pooled median progression-free survival (PFS) were calculated with 95% confidence intervals (CI). Complete response to TKIs was extremely rare (0.3%). The highest PR rate and longest PFS were observed for lenvatinib in differentiated thyroid cancer (69%, 95% CI: 57-81 and 19 months, 95% CI: 9-29, respectively) and vandetanib in medullary thyroid cancer (40%, 95% CI: 25-56 and 31 months, 95% CI: 19-43, respectively). Although the discontinuation rate due to AEs was similar for each TKI, there was a difference in the most frequently observed AE for each TKI (hand-foot syndrome for sorafenib, hypertension and proteinuria for lenvatinib, and QTc prolongation for vandetanib). The identified differences in the TKI efficacy and AE profiles may provide a better understanding of thyroid cancer treatment. Although TKIs are promising agents for thyroid cancer treatment, they are unlikely to lead to a cure. Thus, even in the TKI era, a multimodal treatment including surgery, radioiodine therapy, external beam radiotherapy, and TKIs is required to optimize patient chances of improved survival.

The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis.

The trans-Golgi network (TGN) functions as a hub organelle in the exocytosis of clathrin-coated membrane vesicles, and SMAP2 is an Arf GTPase-activating protein that binds to both clathrin and the clathrin assembly protein (CALM). In the present study, SMAP2 is detected on the TGN in the pachytene spermatocyte to the round spermatid stages of spermatogenesis. Gene targeting reveals that SMAP2-deficient male mice are healthy and survive to adulthood but are infertile and exhibit globozoospermia. In SMAP2-deficient spermatids, the diameter of proacrosomal vesicles budding from TGN increases, TGN structures are distorted, acrosome formation is severely impaired, and reorganization of the nucleus does not proceed properly. CALM functions to regulate vesicle sizes, and this study shows that CALM is not recruited to the TGN in the absence of SMAP2. Furthermore, syntaxin2, a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, is not properly concentrated at the site of acrosome formation. Thus this study reveals a link between SMAP2 and CALM/syntaxin2 in clathrin-coated vesicle formation from the TGN and subsequent acrosome formation. SMAP2-deficient mice provide a model for globozoospermia in humans.

Three-dimensional CT angiography of the hepatic artery: use of multi-detector row helical CT and a contrast agent.

The administration of a contrast agent to obtain optimal images at three-dimensional computed tomographic (CT) angiography of the hepatic artery by using multi-detector row helical CT was investigated. Three-dimensional CT angiographic images were evaluated visually, and quantitative evaluation was performed by measuring the postcontrast CT number of the aorta. The injection rate of 5 mL/sec was significantly superior to that of 4 mL/sec in both evaluations. At administration of a contrast agent with 300 or 350 milligrams of iodine per milliliter, there were no significant differences in either evaluations. The preferable injection rate to obtain sufficient three-dimensional CT angiographic data was 5 mL/sec.