COVID-19 Vaccination in Patients with Cancer.

Patients with cancer are concerned about the effects of the COVID-19 vaccination. We conducted an online survey on the COVID-19 vaccination status and side effects among patients with cancer in Japan between 8 and 14 August 2021. We included 1182 female patients with cancer aged 20-70 years and registered on an online patient website. Of the patients, 944 had breast cancer, 216 had gynecological cancer, 798 were undergoing drug/radiation therapy, and 370 were in follow-up. At the time of the survey, 885 patients had already received at least one dose. Of these, 580 had also received their second dose. The incidence rate of side effects was equivalent to previous reports. In patients with breast cancer, problems such as the onset or worsening of lymphedema or axillary lymphadenopathy metastasis requiring differential diagnosis were encountered following vaccination. A total of 768 patients were concerned about the vaccine at some point, and 726 consulted with their attending physicians about the timing or side effects of the vaccination. Of the 110 patients undergoing chemotherapy or radiation therapy, 75 adjusted the timing of the vaccination based on their therapy. The cross-analysis revealed that 81% of those who consulted their physician had received at least one dose of the COVID-19 vaccination compared with 65% of those who had not consulted their physician. Consulting with a physician about the COVID-19 vaccination was found to alleviate the concerns of patients with cancer and encourage them to get vaccinated.

Epstein-Barr Virus Lytic Reactivation Induces IgG4 Production by Host B Lymphocytes in Graves' Disease Patients and Controls: A Subset of Graves' Disease Is an IgG4-Related Disease-Like Condition.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory disease with characteristic histological findings and high serum IgG4 levels. Epstein-Barr virus (EBV) is a persistent herpesvirus in B lymphocytes, and we previously reported EBV reactivation-induced Ig production. We showed that EBV reactivation induced the production of thyrotropin receptor antibodies, the causative antibodies of Graves' disease. In the present study, we investigated whether EBV reactivation induced IgG4 production and if EBV-positive B cells or IgG4-positive plasma cells are present in the thyroid tissues of Graves' disease patients with lymphoplasmacytic infiltration. EBV-encoded small RNA1 (EBER1) in situ hybridization and immunohistochemistry for IgG and IgG4 were performed on seven resected thyroid tissues with lymphoplasmacytic infiltration collected from the thyroids of 11 Graves' disease patients. We then cultured the lymphocytes of 13 Graves' disease patients and 14 controls and induced EBV reactivation to measure IgG4 levels in culture fluids. We detected EBER1-positive cells and IgG4-positive plasma cells in the same area of thyroid tissues. EBV-reactivated cells with IgG4 on their surface were observed in culture cells, and IgG4 production was detected in culture fluids. The IgG4/IgG percentage was higher than that in normal serum level. A subset of Graves' disease is an IgG4-RD-like condition, not an IgG4-RD. EBV reactivation stimulates IgG4 production, which may result in high serum IgG4 levels and promote IgG4-positive plasma cell infiltration. EBER1 needs to be examined when an increase in IgG4-positive plasma cell numbers is noted.

Correlation between Ultrasound Findings of Tumor Margin and Clinicopathological Findings in Patients with Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Breast ultrasound findings regarding tumor margins are crucial in judging whether a tumor is malignant or benign. However, the relationships between the margins and clinicopathological characteristics remain largely unknown. In this study, we examined the clinicopathological characteristics of patients with invasive ductal carcinoma whose ultrasound images showed either well-defined and rough or indistinct margins. METHODS: Of all consecutive patients diagnosed with invasive ductal carcinoma at the Division of Breast and Endocrine Surgery of Tottori University Hospital from January 2012 to December 2014, 122 patients whose ultrasound images showed either "well-defined and rough" or "indistinct" tumor margins were included in this study. Mammography and ultrasound images taken at the initial examination were reviewed. Patients were divided into two groups based on ultrasound findings of the tumor margins: the "well-defined and rough group" and the "indistinct group." The relationships among ultrasound findings, mammography findings and clinicopathological findings were investigated in the two groups. RESULTS: The well-defined and rough group was more likely to contain solid-tubular carcinoma, while the indistinct group was more likely to contain scirrhous carcinoma. The MIB-1 index was higher in the well-defined and rough group than in the indistinct group. Additionally, the proportion of patients with nuclear grade 3, estrogen receptor-negative/progesterone receptor-negative, and triple-negative breast cancer was greater in the well-defined and rough group than in the indistinct group. CONCLUSION: Invasive ductal carcinomas with well-defined and rough margins on ultrasound were likely to be malignant and proliferative than those with indistinct margins.

Microcalcification of Tumor is a Predictor of Response to Neoadjuvant Chemotherapy for Invasive Breast Carcinoma.

BACKGROUND: In recent years, neoadjuvant chemotherapy (NAC) is often performed for patients with unresectable breast carcinoma or without indication of breast conserving therapy. However, it is currently difficult to predict response to NAC with diagnostic imaging of breast carcinoma. In this study, we investigated imaging findings that could serve as a predictor of the response to NAC for patients with invasive breast carcinoma. METHODS: Twenty-six patients with invasive breast carcinoma who received NAC at the Division of Breast and Endocrine Surgery of Tottori University Hospital between January 2010 and May 2014 were retrospectively investigated. Their imaging findings from mammograms and ultrasonograms were reviewed. The association between findings on mammograms and ultrasonograms captured before NAC and response to treatment after NAC was examined. RESULTS: Of the 26 patients with invasive breast carcinoma, 19 (73%) responded well to treatment and 7 (27%) did not. Most notably, all 10 patients who had microcalcifications on mammogram responded well to treatment (53% of responders), and all patients who did not respond to treatment had no microcalcifications (P < 0.05). Of these 10 patients, 9 (90%) had microcalcifications of comedo type and one (10%) had non comedo type. As a distribution, 8 of the 10 (80%) had a clustered type of microcalcifications and the remaining 2 (20%) had a segmental type of them. CONCLUSION: Microcalcifications of tumor observed in mammogram (particularly comedo type) could be a predictor of response to NAC for patients with invasive breast carcinoma.

Clinical Significance of Microcalcifications Detection in Invasive Breast Carcinoma.

BACKGROUND: Recently, a lot of cases with microcalcifications of the breast are pointed by the images of mammography (MG), because breast screening using MG become common. Although MG is a gold standard modality for detecting microcalcifications, images of ultrasonography (US) are now feasible to detect microcalcifications with recent improvements to ultrasound diagnostic devices. In this report, we analyzed clinical significance of microcalcifications detected with US images in invasive breast carcinoma. METHODS: Eighty-eight patients with invasive breast carcinoma who underwent MG and US before surgery at the Division of Breast and Endocrine Surgery of Tottori University Hospital between January 2012 and August 2013. After reviewing US images, the association between the presence of echogenic spots that indicate microcalcifications and images of MG or pathological findings was assessed. RESULTS: Patients without microcalcifications on US images were significantly more likely to have the Luminal A subtype and a lower nuclear grading. Conversely, patients with microcalcifications on US images were significantly more likely to have higher level of MIB-1 index, lymphovascular invasion, comedonecrosis and lymph node metastasis. The rate of detecting microcalcifications on US images was relatively good, with 81.8% of sensitivity, 94.5% of specificity and 89.8% of diagnostic accuracy. Among the calcifications detected by MG images, detected rate of calcifications with US images was higher in necrotic type (92.6%) than secretory type (33.3%). CONCLUSION: This study suggest that microcalcifications of tumors detected by US images could serve as an useful prediction to evaluate the degree of malignancy for patients with invasive breast carcinoma.

Thyroidectomy in a patient with thyroid storm: report of a case.

Thyroid storm is a life-threatening condition that is generally considered to be a contradiction to surgical intervention. We herein describe the case of a 37-year-old patient with a history of Graves' disease who was transferred to Tottori University Hospital with thyroid storm. She had been followed by her family doctor since 2006, but she had stopped taking her medication of her own volition in 2010. About ten days prior to her admission at our hospital, she consulted her family doctor with complaints of dyspnea, palpitations and general fatigue. Subsequent thyroid function tests showed TSH < 0.01 µU/ml, FT3 25.0 pg/ml and FT4 8.0 ng/dl. She also had acute heart failure, atrial fibrillation and hepatic failure. A diagnosis of thyroid storm was made and she was transferred to our hospital. She received steroids, beta blockade, potassium iodide, and plasma exchange, but her hepatic failure did not resolve and her clinical condition deteriorated. The decision was made to proceed with thyroidectomy. Postoperatively, her hepatic function normalized. Thus, thyroidectomy is a potential therapeutic choice for cases of thyroid storm refractory to medical management.

Implication of intracellular localization of transcriptional repressor PLZF in thyroid neoplasms.

BACKGROUND: Promyelocytic leukaemia zinc finger (PLZF) is a transcriptional repressor that was originally isolated from a patient with promyelocytic leukaemia. PLZF also affects key elements for cell cycle progression, such as cyclin A, and can affect the tumourigenicity of various cancers. Thus far, the behaviour of PLZF in thyroid carcinoma remains unclear. METHODS: We analysed the expression profile of PLZF in different types of benign and malignant thyroid lesions as well as in normal thyroid tissue. Specifically, we examined PLZF expression in normal thyroid (N; n = 4), adenomatous lesion (AL; n = 5), follicular adenoma (FA; n = 2), papillary thyroid carcinoma (PTC; n = 20), and anaplastic thyroid carcinoma (ATC; n = 3) samples. PLZF expression was estimated by western blotting and immunohistochemical (IHC) staining. RESULTS: PLZF was expressed in all samples of thyroid lesions examined. In N, AL, and FA, PLZF was mainly localized in the nucleus. In contrast, in PTC and ATC, PLZF was mainly expressed in the cytosol with high intensity. In more detail, the cytoplasmic IHC scores in PTC with capsular invasion (CI) and lymph node (LN) metastasis were higher than those in PTC without CI and LN metastasis. CONCLUSIONS: PLZF shows different subcellular localizations among PTC, ATC, and other thyroid lesions. Furthermore, high cytoplasmic expression of PLZF may be correlated with CI and LN metastasis in thyroid carcinoma. The present report is the first to describe the implications of intracellular PLZF expression in thyroid carcinomas.

Thymic metastasis of breast cancer 22 years after surgery: a case report.

We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18-fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen-section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.

Effect of chemotherapy for luminal a breast cancer.

BACKGROUND: The addition of chemotherapy to endocrine therapy for luminal A breast cancer generally provides little benefit. However, the least benefit of chemotherapy in all patients with luminal A breast cancer is controversial. METHODS: This was a retrospective study of 140 patients with luminal A breast cancer who underwent surgery at Tottori University Hospital between 2001 and 2010. Luminal A breast cancer was defined as positive for estrogen receptors and/or progesterone receptors and negative for human epidermal growth factor 2. Postoperative endocrine therapy was given to all patients. The prognostic values of age, tumor size, presence of lymphovascular invasion and lymph node status were evaluated. In addition, the prognostic value of chemotherapy for patients with identified risk factors affecting relapse-free survival and overall survival was evaluated. RESULTS: Tumor size greater than 2 cm and positive lymph node status were factors significantly affecting relapse-free survival. There were no factors significantly affecting overall survival. There was no significant difference in the relapse-free survival of patients with tumor size greater than 2 cm and/or positive lymph node status who either received chemotherapy or not. However, the relapse event was earlier in patients with tumor size greater than 2 cm and positive lymph node status who did not receive chemotherapy than in those who received chemotherapy. CONCLUSION: Chemotherapy could provide little benefit to patients with luminal A breast cancer. However, chemotherapy may bring them longer relapse-free periods.

Autoantibody against WD repeat domain 1 is a novel serological biomarker for screening of thyroid neoplasia.

BACKGROUND: Thyroid nodules are common among adults, and accurate diagnosis is critical in for management decisions. Ultrasound and fine needle aspiration cytology are the most common methods to evaluate nodules, but they are not practical for screening large numbers of patients because of cost and time considerations. OBJECTIVE: The aim of this study was to isolate an autoantibody to tumour antigen, WD repeat domain 1 (WDR1), and evaluate its diagnostic sensitivity and specificity for thyroid neoplasms. PATIENTS AND METHODS: We investigated serological biomarkers in patients with thyroid carcinoma who had a poor prognosis. Using a serological analysis of recombinant cDNA expression cloning (SEREX) strategy, we isolated WDR1 and its specific autoantibody in the sera of patients with undifferentiated thyroid carcinoma (UTC). We examined using indirect ELISA, the titre of the anti-WDR1 antibody (AWA) in 54 study patients: 10 with UTC, 20 with papillary thyroid carcinoma (PTC), 17 with benign thyroid nodule (BTN), 7 with autoimmune thyroid disease (AITD), as well as 38 controls (N). RESULTS: WDR1 was ubiquitously expressed in various types of thyroid tissues. However, the titre of AWA in UTC and PTC was significantly higher than that in BTN, AITD and N (P < 0·001). No significant correlation was observed between thyroid function, serum thyroglobulin and tumour diameter. The cut-off value estimated using ROC to differentiate malignancies from others was 0·95 (sensitivity 96·7%, specificity 91·9%, AUC 0·969, P < 0·001). CONCLUSIONS: Anti-WDR1 antibody could be a novel approach for serological screening of PTC and UTC, and could be an efficient and inexpensive biomarker.

Pheochromocytoma multisystem crisis successfully treated by emergency surgery: report of a case.

Pheochromocytomas are rare neuroendocrine tumors that produce symptoms through the excess release of catecholamines. The treatment of choice is a complete surgical removal after pretreatment with an α-blocker, to prevent dangerous hemodynamic fluctuations. Newell and colleagues defined the rare, fatal condition of catecholamine crisis, which includes multiple organ failure (MOF), severe blood pressure variability, high fever, and encephalopathy, as pheochromocytoma multisystem crisis (PMC). The indications for emergency surgery in this unstable state still remain controversial. This report presents the case of a 52-year-old female patient with PMC who successfully underwent a surgical resection. This case showed that early tumor removal may be the only means of halting the progression of this disease.

ACTH-Producing Breast Cancer: A Patient Report.

Ectopic ACTH secretion in the setting of breast cancer is extremely rare but when present affects both the tumor's behavior and the incidence of complications. The patient, a 58-year-old woman, first presented with a mass in her left breast as well as multiple osseous metastases and a right femur fracture. Laboratory data revealed a hypokalemic alkalosis. Her plasma ACTH level was elevated. She was diagnosed with breast cancer with ectopic ACTH secretion, and underwent a left mastectomy and axillary lymph node dissection. Histological examination demonstrated a poorly differentiated neuroendocrine carcinoma with ectopic ACTH secretion. Although the signs and symptoms of ectopic ACTH secretion from a breast cancer are frequently subtle, the recognition of ectopic ACTH secretion from breast cancer is important for patient management.

[A case of aggressive primary squamous cell carcinoma of the breast refractory to preoperative neoadjuvant chemotherapy].

A 42-year-old woman came to our hospital complaining of an enlarging tumor in her right breast. A core needle biopsy of the involved area demonstrated primary squamous cell carcinoma (SCC) of the breast. Preoperative neoadjuvant chemotherapies included 5-fluorouracil: 5-FU+epirubicin: EPI+cyclophosphamide: CPA (FEC), paclitaxel (PTX), vinorelbine (VNR) and 5-FU+nedaplatin (254-S) given in the order listed, but the mass continued to enlarge. Therefore, surgical resection was performed. Local recurrence and lung metastasis occurred after surgery. Although postoperative adjuvant chemotherapy consisting of carboplatin (CBDCA) +etoposide (VP-16) was administered, the patient died three months after surgery. SCC of the breast is generally treated according to clinical stage using protocol for common types of breast cancer. However, effective regimens have not been established for SCC, because it tends to be treatment-refractory. Therefore, in patients with SCC, it is important to consider surgery at an earlier stage than would be considered for a common breast cancer requiring preoperative neoadjuvant chemotherapy.

[A case of locally advanced breast cancer successfully treated by pre-operative systemic therapy using paclitaxel and trastuzumab].

A 53-year-old woman with locally advanced breast cancer exhibiting skin edema and axial lymph-node swelling was treated by pre-operative systemic therapy. A core needle biopsy revealed the tumor to be a solid-tubular carcinoma which was hormone receptor-negative and HER2-positive. Six courses of an anthracycline-based regimen (5-fluorouracil, epirubicin, cyclophosphamide; FEC) and 6 weekly courses of paclitaxel concomitant with trastuzumab were sequentially administered. After those treatments, the tumor presented as clinically CR. An incisional biopsy of the left breast showed that the tumor was completely eliminated, with ductal carcinoma absent upon pathological examination.

Needle track dissemination of follicular thyroid carcinoma following fine-needle aspiration biopsy: report of a case.

Few reports have been concerned with the risk of needle track dissemination of tumor cells following fine-needle aspiration biopsy, especially for follicular thyroid nodules. A 61-year-old woman who underwent fine-needle aspiration biopsy and surgery 5 years previously for follicular thyroid adenoma presented with nodules that had developed in the sternocleidomastoid and omohyoid muscles of the anterior neck. These nodules were located along a line from the skin to the thyroid that coincided with the needle track of the previous biopsy. Following surgical resection, histological diagnosis determined the nodules to be follicular carcinoma. The clinical course and linear arrangement of the lesions were highly suggestive of needle track dissemination of tumor cells following fine-needle aspiration biopsy. Although fine-needle aspiration biopsy is a useful tool for the diagnosis of thyroid nodules, it is important to consider the risk of tumor cell dissemination.

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ø) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.

[Evaluation of safety and efficacy for bi-weekly Docetaxel and 5'-DFUR combination therapy in patients with advanced or recurrent breast cancer--Phase I study].

BACKGROUND: A clinical trial of Docetaxel was performed by tri-weekly administration in patients with advanced or recurrent breast cancer. However, careful observation is necessary for outpatients because serious neutropenia often occurs during the therapy. A bi-weekly schedule is recommended since weekly administration requires more visits to the hospital. Docetaxel is proved to express synergistic efficacy in combination with 5'-DFUR by induced dThdPase in vivo. But there are no clinical trials to evaluate efficacy of bi-weekly Docetaxel and 5'-DFUR combination therapy. PURPOSE: To evaluate safety, the recommended dose of Docetaxel and the efficacy of biweekly Docetaxel and 5'-DFUR combination therapy. PATIENTS AND METHODS: Patients with advanced or recurrent breast cancer within 1 regimen of prior chemotherapy and without prior use of both Docetaxel and 5'-DFUR were enrolled. 5'-DFUR was orally administered by 600 mg/day. Docetaxel was intravenously given for at least 2 cycles (8 weeks) by 30 mg/m(2) for level 1, 40 mg/m(2) for level 2 and 50 mg/m(2) for level 3. At each level with 3 cases enrolled,the maximum tolerated dose (MTD) level was defined as that in which 2 or 3 cases showed dose limiting toxicity (DLT). The recommended dose was defined as the dose before MTD level. Therapeutic safety was evaluated by analyses of adverse events with the recommended dose. RESULTS: MTD was in level 3 and the recommended dose of Docetaxel was 40 mg/m(2) of level 2. No DLT was observed in level 2, and this combination therapy seemed safe and feasible for outpatients. In addition, all 6 cases for whom therapeutic efficacy was evaluated expressed a clinical response.

Laparoscopic bilateral partial adrenalectomy for adrenocortical adenomas causing Cushing's syndrome: report of a case.

Laparoscopic total adrenalectomy has become a standard technique for small adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenocortical function in a 41-year-old woman with bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome, we performed laparoscopic bilateral partial adrenalectomy. We based our preoperative diagnosis of bilateral adrenocortical tumors causing Cushing's syndrome on the results of endocrinological investigations and imaging findings. Thus, we performed lateral transperitoneal laparoscopic bilateral partial adrenalectomy, preserving the adrenal glands, which were normal. Pathological examination of both tumors confirmed the diagnosis of adrenocortical adenoma. The patient had no postoperative complications, and her adrenocortical function was normal without steroid replacement at her 10-month follow-up. This report shows that Cushing's syndrome resulting from bilateral adenomas can be effectively treated by laparoscopic bilateral partial adrenalectomy as a minimally invasive, adrenocortical-preserving operation.