Development of a Rapid Intraoperative Point-of-Care Method Using Tissue Suspension to Differentiate Parathyroid Tissue: A Possible Substitute for Frozen Sections.

BACKGROUND: We reported that aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio of a tissue suspension can precisely differentiate normal and hyperfunctioning parathyroid tissue (PT) from other tissues. However, in these studies, LDH and AST were measured using the standard method for blood samples, with a turnaround time of approximately 1 h, hampering clinical application. Here, we developed a rapid and robust method to differentiate PT instead of using frozen sections. METHODS: Excised specimens from 28 patients (n = 69) who underwent thyroid or parathyroid surgery between October 2019 and April 2020 were analyzed. AST and LDH were measured in suspensions of PT or other tissues, using both the standard method in the in-facility laboratory and a point-of-care testing device (NX500, Fujifilm, Japan). RESULTS AND CONCLUSIONS: A good correlation was found between the standard method and NX500 for AST and LDH levels >10 IU/L. In the analyses using 52 specimens with ≥ 10 IU/L of both AST and LDH measured using the NX500, PT was distinguished with 100% sensitivity and specificity using an optimal cutoff AST/LDH ratio of 0.48. The turnaround time was estimated to be less than 10 min. This method could be a cost- and labor-effective alternative to frozen sections to reduce the incidence of postoperative hypoparathyroidism and improve the outcome of primary hyperparathyroidism in low-resource areas.

Identifying the tumor-progressive gene expression profile in high-risk papillary thyroid cancer.

PURPOSE: Papillary thyroid cancer (PTC) is generally associated with a favorable prognosis. However, some patients have fatal disease, with locally infiltrating tumors or progressive distant metastases; yet few studies have investigated the characteristics of the tumor-progressive gene expression profile in advanced PTC. We conducted this study to clarify the gene expression status in advanced PTC and identify candidate molecules for prognostic biomarkers. METHODS: We analyzed 740 tumor-progressive gene expression levels from formalin-fixed paraffin-embedded blocks of samples from six patients with low-risk PTC and six patients with high-risk PTC, using the nCounter PanCancer Progression panel. Then, we investigated the association between the expression levels of focused genes and pathological factors in PTC patients in The Cancer Genome Atlas (TCGA) database. RESULTS: The expression levels of 14 genes in the high-risk PTC specimens were more than two-fold those in the low-risk PTC specimens. In the TCGA database, expression levels of four genes (CCL11, COL6A3, INHBA, and SRPX2) were significantly higher in patients with advanced PTC. Among the patients with advanced PTC, those with high SRPX2 expression levels had poor disease-free survival. Univariate and multivariate analyses revealed that high SRPX2 expression was an independent prognostic factor. CONCLUSION: Based on the findings of this study, CCL11, COL6A3, INHBA, and SRPX2 are potential biomarkers that indicate advanced PTC. SRPX2, in particular, is considered a prognostic biomarker.

Clinical value of serum bone resorption markers for predicting clinical outcomes after use of bone modifying agents in metastatic bone tumors: A prospective cohort study.

Bone modifying agents (BMAs) have become a standard treatment to prevent skeletal-related events (SREs) in bone metastases (BMs). The aim of our study is to determine the clinical value of serum bone resorption markers for predicting clinical outcomes after using BMAs in patients with BM. Patients were enrolled between May 2013 and October 2017 at the Nagoya University Hospital, Japan. We prospectively observed changes in pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) during treatment with BMAs. The relationship between serum markers before and after treatment and clinical outcomes such as progression of bone disease (BD), SREs and overall survival (OS) were evaluated. Pearson chi-square test and Kaplan-Meier product limit methods were used for analysis. Sixty-seven patients were analyzed. The primary tumor sites were 21 lung, 16 breast and 30 others. Forty and 27 patients were treated with Denosumab and Zoledronic acid, respectively. Progression of BDs, SREs and death were observed in 10, 16 and 31 cases, respectively. The median follow-up period after using BMAs was 12.3 (range 0.3-66.3) months. ICTP at 3-4 weeks was significantly correlated with increasing BD progression, SREs and death after treatment in both the whole and lung cancer cohorts. Base line ICTP and TRACP-5b were also associated with increasing BD progression in the whole cohort. Our study showed that early posttreatment ICTP is useful for predicting BD progression, SREs and OS after use of BMAs in patients with BM and even in patients with lung cancer BM.

Multicenter Phase II Study of Intraoperative Radiotherapy of Early Breast Cancer: Ipsilateral Tumor Recurrence.

BACKGROUND: We performed a multicenter phase II study on the efficacy and safety of intraoperative radiotherapy (IORT) as partial breast irradiation using multiple devices. METHODS: The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Key inclusion criteria were T < 2.5 cm, age > 50 years, surgical margin > 1 cm, intraoperative pathologically free margins, and sentinel node negative. After resection of the tumor, radiation at 21 Gy was delivered directly to the mammary gland employing an electron linear accelerator in the operating room, otherwise the patient was transported from the surgical suite to the radiation room. RESULTS: Overall, 142 patients were enrolled in this study and 129 underwent IORT. Stage 0: n = 4 (3.1%); stage I: n = 98 (76.0%); and stage IIA: n = 27 (20.9%). Luminal type: n = 116 (89.9%); triple-negative: n = 9 (7.0%); and human epidermal growth factor receptor 2: n = 4 (3.1%). Median follow-up time was 59.5 months (range 27.5-99.0), and the rate of IBTR was 3.1% (95% confidence interval 0.9-7.8). The toxicities included fibrosis in deep-connective tissue: grade 1, 78.1%; wound infection: grade 3, 1.6% and grade 2, 1.6%; and soft tissue necrosis: grade 3, 0.8% and grade 2, 0.8%. Recurrence in the breast occurred in four cases; the site of recurrence was just under the skin near the primary tumor site, with similar histology and subtype. CONCLUSIONS: In this multicenter phase II study, the rate of IBTR was low and IORT at 21 Gy was feasible in properly selected patients. It is important to use a careful surgical technique to reduce local recurrence because the skin is not included in the radiation field of IORT.

Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin chemotherapy in breast cancer mouse models.

PURPOSE: Circulating tumor cells (CTCs) can provide a potentially minimal invasive source for monitoring chemotherapeutic effects. However, detailed in vivo dynamics of CTC after chemotherapy remain largely unknown. METHODS: We monitored CTC number and morphology early after chemotherapy using a newly developed cytology-based CTC detection device and triple-negative breast cancer mouse CTC models with spontaneous lung metastatic potential. RESULTS: Paclitaxel inhibited cell growth of breast cancer cells by mainly G2/M cell cycle arrest and partly apoptosis, whereas doxorubicin inhibited cell growth mainly by apoptosis and partly G2 cell cycle arrest in vitro. The number of CTCs was significantly increased 3-10 days after paclitaxel and doxorubicin chemotherapy and decreased thereafter in two mouse CTC models. The transiently increased CTCs early post-chemotherapy consisted of not only G2/M arrested cells (apoptotic cells), but also morphologically near-intact live cells. This heterogeneous cell population of CTCs was similar to that of primary tumor tissue after chemotherapy. CONCLUSIONS: These results indicate that CTCs can be mobilized from the primary tumor in rapid response to chemotherapy and suggest the possibility that CTC monitoring from both numerical and morphological viewpoints early after chemotherapy using a cytology-based CTC detection device would be a useful diagnostic tool for predicting drug sensitivity/resistance in preclinical and clinical setting.

Feasibility of dose-dense epirubicin and cyclophosphamide with subcutaneous pegfilgrastim 3.6 mg support: a single-center prospective study in Japan.

BACKGROUND: Dose-dense chemotherapy consisting of a combination of epirubicin and cyclophosphamide (EC) improves the survival of patients with breast cancer. Although pegfilgrastim was used at a subcutaneous dose of 6.0 mg in a pivotal study of dose-dense EC treatment, pegfilgrastim at a dose of 3.6 mg has been approved in Japan. We have assessed the feasibility of dose-dense EC treatment supported with a 3.6 mg dose of pegfilgrastim by evaluating the relative dose intensity (RDI) and safety of the treatment, together with measuring the pegfilgrastim concentrations remaining on the day of starting the next cycle of chemotherapy. METHODS: Patients with primary breast cancer received a total of 4 cycles of dose-dense EC treatment every 2 weeks, together with a subcutaneous injection of 3.6 mg pegfilgrastim on the day after chemotherapy. The serum granulocyte colony-stimulating factor (G-CSF) concentrations were measured on the 15th day of every chemotherapy cycle. RESULTS: From March 2015 through to July 2016, a total of 51 patients (median age 51 years; range 33-73 years) were studied. The mean RDI was 95.2% (range 60.0-100%). Although most adverse events were consistent with those reported in previous studies, pneumocystis pneumonia developed in two patients during the following course of docetaxel treatment. The median serum G-CSF concentration was 92.5 (range 30.4-440) pg/ml. CONCLUSIONS: With support provided by pegfilgrastim injection at a dose of 3.6 mg, dose-dense EC is feasible and associated with maintenance of a high RDI. There was no clinically significant accumulation of serum G-CSF concentrations associated with the use of a 3.6 mg dose of pegfilgrastim at 2-week intervals.

Obesity does not affect peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy.

Laparoscopic adrenalectomy is the gold standard procedure for most adrenal tumors. Obesity is considered as a risk factor for surgical complications. This study aimed to evaluate whether obesity affects peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy using body mass index (BMI). This retrospective study included 98 patients who underwent transabdominal laparoscopic adrenalectomy between January 2011 and December 2016. We divided the patients into 2 groups: non-obese group (BMI < 25 kg/m2) and obese group (BMI ≥ 25 kg/m2). We assessed perioperative outcomes and postoperative complications between the groups. A total of 98 patients were analyzed (70 without obesity and 28 with obesity). There were no significant differences between the non-obese and obese groups regarding operative time (111 vs 107 min; p = 0.795), blood loss (3.5 vs 3.5 ml; p = 0.740), rate of placement of additional trocars (14.3% vs 17.9%; p = 0.657), rate of open conversion (2.6% vs 3.6%; p = 0.853), and postoperative length of hospital stay (6 vs 5 days; p = 0.237). Furthermore, obesity was not a significant risk factor for postoperative complications (postoperative bleeding, wound infection, and pneumonia). There are no significant differences in peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy in patients with obesity compared with those without obesity. Transabdominal laparoscopic adrenalectomy is feasible and safe for patients with obesity.

Multi-center rater-blinded study of early intervention with the Hand Incubator for breast cancer-related lymphedema (the BEAT-EDEMA trial): Proposal of a research protocol.

Postoperative lymphedema is considered irreversible once it has developed, and significantly lowers the patient's quality of life. However, lymphatic function has recently been clarified, and it is possible that lymphedema can be cured if early treatment is started. This two-arm randomized clinical trial (UMIN000026124) will prospectively evaluate 24 patients with early-stage breast cancer-related lymphedema at the Nagoya University Hospital and Aichi Cancer Center Hospital. The eligibility criteria will be patients who are diagnosed with stage 0-1 breast cancer-related lymphedema, as defined by the International Society of Lymphology, within 12 weeks after breast cancer surgery. The diagnosis of lymphedema will be confirmed using a bioimpedance spectroscopy device (L-Dex®). Participants will be randomized 1:1 into the intervention and control groups. The physicians and patients will be aware of their group assignment, although treatment efficacy will be evaluated by raters who are blinded to the group assignments. The intervention group will complete grasping exercises in the Hand Incubator device for 4 weeks. The primary outcome will be the change in the affected upper limb's volume after the intervention, as measured using the water displacement method. This study may help establish a standard treatment for postoperative lymphedema.

Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma.

BACKGROUND: The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. METHODS: Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. RESULTS: The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9% and 88.4% for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6% and 93.1% for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. CONCLUSIONS: Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC.

Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft.

Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment.

Background parenchymal enhancement in preoperative breast MRI.

We aimed to assess the influence of background parenchymal enhancement (BPE) on surgical planning performed using preoperative MRI for breast cancer evaluation. Between January 2009 and December 2010, 91 newly diagnosed breast cancer patients (mean age, 55.5 years; range, 30-88 years) who underwent preoperative bilateral breast MRI followed by planned breast conservation therapy were retrospectively enrolled. MRI was performed to assess the tumor extent in addition to mammography and breast ultrasonography. BPE in the contralateral normal breast MRI at the early dynamic phase was visually classified as follows: minimal (n=49), mild (n=27), moderate (n=7), and marked (n=8). The correlations between the BPE grade and age, menopausal status, index tumor size, changes in surgical management based on MRI results, positive predictive value (PPV) of MRI, and surgical margins were assessed. Patients in the strong BPE groups were significantly younger (p=0.002) and generally premenopausal (p<0.001). Surgical treatment was not changed in 67 cases (73.6%), while extended excision and mastectomy were performed in 12 cases (13.2%), each based on additional lesions on MRI. Six of 79 (7.6%) patients who underwent breast conservation therapy had tumor-positive resection margins. In cases where surgical management was changed, the PPV for MRI-detected foci was high in the minimal (91.7%) and mild groups (66.7%), and 0% in the moderate and marked groups (p=0.002). Strong BPE causes false-positive MRI findings and may lead to overly extensive surgery, whereas MRI may be beneficial in select patients with weak BPE.

Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic accuracy and strategies for Japanese patients.

Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.

Phase I Dose-escalation Clinical Trial of HF10 Oncolytic Herpes Virus in 17 Japanese Patients with Advanced Cancer.

Oncolytic virus therapy is a promising new therapeutic method, one of an eagerly anticipated class of biological therapies against cancer. There are many different classes of oncolytic virus. One of these, herpes oncolytic virus, is strongly oncolytic and has a large DNA genome as 150k bp. HF10 is a spontaneous mutant of herpes simplex virus -1 (HSV-1) that replicates within tumors and destroys cancers without damaging normal tissue and organs. Clinical trials of HF10 are underway in Japan and the United States. The first pilot study of HF10 was initiated in Japan in 2003. This study examined the safety and efficacy of HF10 in the treatment of breast cancer and head and neck cancers; the trial also included careful dose escalation studies. In 2005, a clinical trial using HF10 to treat pancreatic cancer was initiated. screened In this Japanese study, 17 patients received HF10 in their tumor sites. A clinical trial in the United States is also ongoing to evaluate safety, tolerability and evidence of antitumor activity in patients with refractory superficial solid tumors. Here, we report the evaluation of the 17 patients treated in Japan. Among the patients, 6 had recurrent breast cancer, 3 had recurrent head and neck cancer, and 8 had non-resectable pancreatic cancer. No severe adverse side effects have been observed, and some therapeutic potential has been reported based on pathological findings, tumor markers, and diagnostic radiography. Those results should encourage further clinical trials of HF10 around the world.

Long-term response to MEK inhibitor monotherapy in a patient with papillary thyroid carcinoma harboring BRAF V600E mutation.

Solid tumors harboring mutations in the Braf gene (BRAF) are currently treated by combination Braf/MEK inhibitor therapy, and there is an extensive literature on patient response rates. Alternatively, few studies have documented the clinical response of BRAF mutation-positive solid tumors to MEK inhibitor monotherapy. We report the case of a 57-year-old female diagnosed with papillary thyroid carcinoma and progressive lung metastases initially treated by total thyroidectomy and subsequent thyroid-stimulating hormone suppression therapy. Next-generation sequencing revealed that the tumor harbored a BRAF V600E mutation, and the patient was enrolled in a clinical study of the oral MEK1/2 inhibitor binimetinib. Shortly after starting treatment, the patient experienced pneumothorax due to rapid regression of lung metastases, and computed tomography after 6 months of binimetinib treatment revealed a partial sustained response. One year later, the dose was reduced because of an acneiform rash. After 5 years of binimetinib treatment, lung metastases had regrown, and treatment was switched to the oral multikinase inhibitor lenvatinib. This case demonstrates the potential of MEK inhibitor monotherapy as an alternative treatment for BRAF mutation-positive papillary thyroid carcinoma.

Thymic neuroendocrine tumour in multiple endocrine neoplasia type 1: female patients are not rare exceptions.

OBJECTIVE: Thymic neuroendocrine tumour (Th-NET) occurs in 2-5% of patients with MEN1 and has high malignant potency accompanying recurrence and distant metastasis. While Th-NET is recognized to develop predominantly in men and heavy smokers, a number of female patients have been reported in the literature. The objective of this study is to clarify the clinical features of MEN1 patients with Th-NET using database analysis. DESIGN/PATIENTS: Clinical data of patients with Th-NET were extracted and analysed from a recently constructed database of Japanese MEN1 patients. RESULTS: Among 560 registered cases, Th-NET was seen in 28 (5·0%) patients. Of note, 36% of patients (10/28) were women; only one patient among those was a smoker and another six patients were non-smokers. Age at diagnosis of Th-NET and MEN1, tumour size, prevalence of other MEN1-related tumours did not differ between male and female patients, and 10-year survival probability was 0·271 ± 0·106. CONCLUSIONS: Although the prevalence of Th-NET in women (3·2%) is significantly lower than that in men (7·6%), a considerable proportion of female patients develop Th-NET. Given that Th-NET is a major determinant of life expectancy of patients, our results alert clinicians who treat patients with MEN1 that surveillance of Th-NET is essential even for female patients without a smoking habit.

Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients.

Although postoperative serum thyroglobulin (Tg) is a prognostic indicator for papillary thyroid carcinoma (PTC), it is unreliable when Tg antibody (TgAb) is positive. We evaluated the prognostic significance of changes in serum TgAb levels of pre- and post-total thyroidectomy in TgAb-positive PTC patients. We reviewed our medical charts of 225 TgAb-positive PTC patients in whom TgAb levels were measured before and 1-2 years after total thyroidectomy, performed between April 2002 and March 2007. We divided them into 3 groups based on changes in TgAb levels. Postoperative serum TgAb levels decreased by ≥ 50% in 181 patients (80.4%) (Group 1), by <50% in 22 patients (9.8%) (Group 2), and increased in 22 patients (9.8%) (Group 3). During the follow-up, 3 patients died of the disease and 14 patients had recurrences. All 3 patients who died of PTC were seen only in Groups 2 and 3. Groups 2 and 3 showed similar prognostic outcomes, thus were analyzed together as Group 2+3. Group 1 had significantly better lymph node recurrence-free survival and distant recurrence-free survival than Group 2+3 (96.9% vs. 90.5%, p <0.001, and 98.9% vs. 90.1%, p = 0.004, respectively at 5 years). Multivariate analyses on prognostic factors revealed that classification to Group 2+3 was the strongest indicator for poor prognosis. The present results suggest that changes in TgAb levels following total thyroidectomy can be an important dynamic prognostic factor of PTC patients. Prospective periodical measurements of TgAb are necessary to confirm these findings.

Long-term results of surgery for papillary thyroid carcinoma with local recurrence.

PURPOSE: Surgical treatment of local recurrent papillary thyroid carcinoma is still controversial because of the increased morbidity in comparison to primary surgery, and the unclear efficacy. This study analyzed the efficacy and safety of surgery for recurrent disease. METHODS: A retrospective cohort analysis of 86 patients who underwent surgery for local recurrent papillary thyroid carcinoma at a single institution during the period 1979-2009. RESULTS: The cause-specific survival rates of all patients at 5, 10, and 20 years were 86 % (95 % CI 77-95 %), 74 % (95 % CI 62-87 %), and 36 % (95 % CI 18-54 %), respectively. A univariate analysis found that gender, age >45 years at reoperation and macroscopic non-curative surgery for recurrence affected the cause-specific survival rates. The latter two features remained significant in a multivariate analysis. Permanent recurrent nerve paralysis and hypoparathyroidism developed in 4 (4.7 %) and 5 (5.8 %) patients, respectively. CONCLUSIONS: Surgery for local recurrent papillary thyroid carcinoma could be effective when macroscopic curative dissection was possible, and that the procedure was safe and was associated with minimal morbidity. Therefore, repeat surgery for local recurrent papillary thyroid carcinoma is worthwhile.

Robotic resection of ectopic mediastinal parathyroid adenoma in multiple endocrine neoplasia 1.

BACKGROUND: Hyperparathyroidism in patients with multiple endocrine neoplasia 1 is attributed to the excessive secretion of parathyroid hormone (PTH) from multiple parathyroid glands. This can be successfully treated through complete resection of the parathyroid glands; however, subsequent surgery is often required because of the presence of supernumerary or ectopic parathyroid glands. Therefore, identifying the locations of all functional glands is crucial for precise resection. Here, we report a case of ectopic mediastinal parathyroid adenoma that was successfully resected using robot-assisted thoracoscopic surgery. CASE PRESENTATION: A 53-year-old woman underwent a total parathyroidectomy with autotransplantation for multiple endocrine neoplasia 1-associated primary hyperparathyroidism. The patient previously underwent laparoscopic distal pancreatectomy for a pancreatic neuroendocrine tumor. She also presented with a mediastinal tumor and nonfunctional pituitary adenoma that could be followed up. Blood tests before total parathyroidectomy showed high levels of intact PTH (183 pg/mL) and calcium (Ca; 10.3 mg/dL); however, postoperative blood tests still revealed high levels of intact PTH (103 pg/mL) and Ca (11.4 mg/dL). Computed tomography and magnetic resonance imaging revealed a 45-mm-sized mass in the right upper mediastinum as a well-defined solid and cystic lesion, whereas 99mTc-methoxyisobutylisonitrile scintigraphy indicated a strong accumulation of tracers, suggesting an ectopic lesion in the mediastinum. Persistent hyperparathyroidism after total parathyroidectomy via neck incision was attributed to an ectopic parathyroid tumor in the mediastinum. Thus, we decided to resect the tumor using robot-assisted thoracoscopic surgery to perform the procedure gently and carefully. During surgery, a mediastinal tumor was identified as it was detected radiographically. Because it did not invade the surrounding tissues, it could be completely resected without injuring the capsule. The patient was discharged without complications. Postoperatively, Ca and intact PTH levels decreased back to normal. The final pathological diagnosis confirmed that the mass was an ectopic mediastinal parathyroid adenoma. CONCLUSIONS: Minimally invasive surgical resection of a remnant ectopic lesion was successfully performed in a patient with multiple endocrine neoplasia 1 using robot-assisted thoracoscopic surgery.

Exploring Indicators of Subcutaneous Tissue Fluid Accumulation in Breast Cancer-Related Lymphedema Patients Using Fractal Analysis with Virtual Volume.

Background: Breast cancer treatment sometimes causes a chronic swelling of the arm called breast cancer-related lymphedema (BCRL). Its progression is believed to be irreversible and is accompanied by tissue fibrosis and lipidosis, so preventing lymphedema from progressing by appropriate intervention at the site of fluid accumulation at an early stage is crucial. The tissue structure can be evaluated in real time by ultrasonography, and this study aims at assessing the ability of fractal analysis using virtual volume in detecting fluid accumulation within BCRL subcutaneous tissue via ultrasound imaging. Methods and Results: We worked with 21 women who developed BCRL (International Society of Lymphology stage II) after unilateral breast cancer treatment. Their subcutaneous tissues were scanned with an ultrasound system (Sonosite Edge II; Sonosite, Inc., FUJIFILM) using a 6- to 15-MHz linear transducer. Then, a 3-Tesla MR system was used to confirm fluid accumulation in the corresponding area of the ultrasound system. Significant differences in both H + 2 and complexity were observed among the three groups (with hyperintense area, without hyperintense area, and unaffected side) (p < 0.05). Post hoc analysis (Mann-Whitney U test; Bonferroni correction p < 0.0167) revealed a significant difference for "complexity." The evaluation of the distribution in Euclidean space showed that the variation of the distribution decreased in the order of unaffected, without hyperintense area, and with hyperintense area. Conclusion: The "complexity" of the fractal using virtual volume seems to be an effective indicator of the presence or absence of subcutaneous tissue fluid accumulation in BCRL.