A Case of Acromegaly With Progressed Diabetic Retinopathy and Sarcopenia Diagnosed Following the Onset of Severe Hypoglycemia.

Acromegaly is a rare disorder characterized by excessive production of growth hormone (GH) from a pituitary tumor, typically leading to elevated glucose levels due to increased insulin resistance; hypoglycemia is rare. However, the long-term effect of excess GH on the peripheral organs is still unclear. Here we present a 69-year-old man evaluated for the cause of a hypoglycemic episode. He was underweight (body mass index: 17.3 kg/m2) with sarcopenia, which potentially contributed to his hypoglycemia. Notably, he exhibited progressed proliferative diabetic retinopathy compared to other microvascular complications, leading to further endocrinological investigation. As a result, he was diagnosed with acromegaly showing elevated GH and insulin-like growth factor-1 (IGF-1) with a pituitary tumor. Opting against transsphenoidal surgery (TSS), the patient was treated with a somatostatin analog (SSA), achieving normalized IGF-1 levels with a monthly 120 mg lanreotide injection. In this case, acromegaly could lead to sarcopenia from GH-derived gluconeogenesis in the peripheral organs such as the reduction of muscle leading to reduced glucose reserves. Acromegaly in the elderly may present atypicality. Clinicians should be vigilant for unique manifestations such as advanced diabetic retinopathy, even in elderly patients with hypoglycemia.

Protocol of a phase II study to evaluate the efficacy and safety of deep-inspiration breath-hold daily online adaptive radiotherapy for centrally located lung tumours (PUDDING study).

BACKGROUND: Centrally located lung tumours present a challenge because of their tendency to exhibit symptoms such as airway obstruction, atelectasis, and bleeding. Surgical resection of these tumours often requires sacrificing the lungs, making definitive radiotherapy the preferred alternative to avoid pneumonectomy. However, the proximity of these tumours to mediastinal organs at risk increases the potential for severe adverse events. To mitigate this risk, we propose a dual-method approach: deep inspiration breath-hold (DIBH) radiotherapy combined with adaptive radiotherapy. The aim of this single-centre, single-arm phase II study is to investigate the efficacy and safety of DIBH daily online adaptive radiotherapy. METHODS: Patients diagnosed with centrally located lung tumours according to the International Association for the Study of Lung Cancer recommendations, are enrolled and subjected to DIBH daily online adaptive radiotherapy. The primary endpoint is the one-year cumulative incidence of grade 3 or more severe adverse events, as classified by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). DISCUSSION: Delivering definitive radiotherapy for centrally located lung tumours presents a dilemma between ensuring optimal dose coverage for the planning target volume and the associated increased risk of adverse events. DIBH provides measurable dosimetric benefits by increasing the normal lung volume and distancing the tumour from critical mediastinal organs at risk, leading to reduced toxicity. DIBH adaptive radiotherapy has been proposed as an adjunct treatment option for abdominal and pelvic cancers. If the application of DIBH adaptive radiotherapy to centrally located lung tumours proves successful, this approach could shape future phase III trials and offer novel perspectives in lung tumour radiotherapy. TRIAL REGISTRATION: Registered at the Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/ ); registration number: jRCT1052230085 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1052230085 ).

Robot-assisted radical prostatectomy using the novel hinotoriTM surgical robot system: initial experience and operation learning curve at a single institution.

Background: The hinotoriTM surgical robot system (HSRS) is the first made-in-Japan robotic system used for radical prostatectomy. Here, we report initial results and describe our learning curve (skill development) implementing robot-assisted radical prostatectomy using HSRS (h-RARP). Methods: Between November 2021 and December 2022, 97 patients who underwent h-RARP at our institution were enrolled in this study. We retrospectively evaluated the surgical outcomes of the initial cases using h-RARP, comparing those of RARP using da Vinci surgical robot system (d-RARP) in our institution. Furthermore, the learning curves of two surgeons with the highest number of h-RARP were analyzed. Patients treated by each surgeon were categorized into two groups: 1-15 cases (earlier group) and >15 cases (later group). Preoperative patient characteristics, operation parameters, and complication rates were compared between the two groups. Results: In terms of surgical outcome, h-RARP was comparable to d-RARP. The procedures performed by the HSRS were successfully completed in all cases. There was no complication of grade 3 or higher. Comparing the two surgeons, surgeon 1, who had performed 40 d-RARP procedures, had time using robot system of the later group that was significantly shorter than that of the earlier group. However, for surgeon 2 with more than 100 d-RARP procedures, there was no statistically significant difference in time using robot system between groups. Other parameters showed no difference between earlier and later groups for the two surgeons. Conclusions: Our results show that surgical outcomes of h-RARP are comparable to those of d-RARP during the initial experience of clinical application. In addition, the surgeons' learning curves for the total RARP experience suggest that the experience of d-RARP can carry over to performance using the novel HSRS.

Role of albumin Cys34 redox state in the progression of differentiated thyroid carcinoma and induction of ferroptosis.

Differentiated thyroid cancer (DTC) is the most prevalent endocrine malignancy worldwide and requires effective prognostic markers and therapeutic targets to optimize patient outcomes. This study investigated the potential of human serum albumin (HSA) cysteine-34 (Cys34) redox state as a prognostic indicator and therapeutic avenue for DTC. A retrospective cohort study of 99 patients with DTC undergoing radioactive iodine therapy found that higher concentrations of HSA with the reduced form of Cys34 (i.e., human mercaptalbumin [HMA]) were associated with improved progression-free survival in metastatic DTC. In vitro experiments using a DTC cell line revealed that HMA induced cytotoxic effects by triggering ferroptosis, characterized by lipid peroxidation, intracellular ROS accumulation, and decreased cell viability. Ferroptosis inhibitors rescued cell viability, confirming their role in cytotoxicity. These results implicate the HSA-Cys34 redox state is a promising avenue for precision medicine in DTC, shedding light on the prognostic relevance and therapeutic potential of HMA-induced ferroptosis. They emphasize the opportunity for personalized treatment strategies to advance the management of patients with DTC.

Recurrence-free survival and prognosis after adjuvant therapy with radioactive iodine-131 in patients with differentiated thyroid carcinoma.

This study aimed to assess recurrence-free survival (RFS) rates and recurrence-related factors of patients who received adjuvant therapy (AT) with radioactive iodine (RAI) for differentiated thyroid cancer (DTC) following thyroidectomy. We evaluated 284 patients who underwent AT between January 2011 and July 2020 at our hospital. Recurrence was defined as visible recurrent lesions on image analysis or need for repeat surgery with pathologically confirmed recurrent lesions. RFS rate and prognostic factors were statistically evaluated. The median observation period was 30.2 months (range, 5.7-294 months). Overall, 192 patients were female and 92 were male, and the median age was 54 years (range, 9-85 years). Initial assessment revealed 39 recurrence cases. The 3-year RFS rate was 85.8% (95% confidence interval: 81.1-90.9%). Univariate analysis revealed that histology (except for papillary carcinoma), Tg level > 4 ng/dL before AT, and AT result significantly exacerbated the RFS rate. In multivariate analysis, histology and AT result were also important contributors to the worsening RFS rate. Results of AT can be determined relatively early and are important in predicting future recurrence in patients with DTC. Increasing the success rate of AT may lead to an improved prognosis.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib.

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

A Case Report of Successful Renal Transplantation After Surgically Treated Type A Aortic Dissection.

BACKGROUND: Aortoiliac lesions can influence the results of kidney transplantation and increase technical difficulties during surgery. Aortic dissection (AD) is a rare and infrequently reported event before transplantation, whereas immediate optimal perfusion is paramount for kidney transplantation. Thus, adequate blood flow imposed by the flow from the true lumen must be considered when choosing a target inflow vessel. CASE PRESENTATION: A 67-year-old man on dialysis with end-stage renal disease caused by immunoglobulin A nephropathy was referred for kidney transplantation. He had successfully undergone conventional Stanford type A AD surgery 3 years ago. Pretransplant contrast-enhanced computed tomography angiography revealed termination of the distal intimal flaps within the common iliac arteries. Dilation of the descending aorta was also observed. Based on the meticulous vascular assessment, including consultation with the cardiovascular surgery department, the right internal iliac artery (IIA) was considered usable for anastomosis. He underwent living unrelated kidney transplantation from his 66-year-old wife. The patency and blood flow in the right IIA were also verified using intraoperative findings. Without any special procedure, we used a side-to-end arterial anastomosis between the donor renal artery and recipient IIA. After vascular clamp removal, the allograft was perfused homogeneously and immediately functioned. CONCLUSION: Patients receiving previous surgery for type A AD can successfully undergo kidney transplantation if the patency of the iliac arteries from the true lumen is confirmed by perioperative evaluation, and the artery can be carefully clamped to avoid possible further dissection.

A Case Report of Successful Kidney Transplantation in a Patient With Autosomal Dominant Polycystic Kidney Disease Who Underwent Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with several cardiovascular disorders, including aortic dissection, which preferentially occurs at the thoracic or abdominal level. Because there are few case reports describing surgical repair for aortic dissection followed by renal transplantation in patients with ADPKD, kidney transplantation performed after repair for aortic dissection remains challenging. CASE PRESENTATION: A 34-year-old Japanese man with end-stage renal disease secondary to ADPKD underwent thoracic endovascular aortic repair for complicated acute type B aortic dissection 12 months earlier. A contrast computed tomography scan before transplantation revealed an aortic dissection involving the descending aorta proximal to the common iliac arteries and confirmed multiple large bilateral renal cysts. After simultaneous right native nephrectomy, the patient underwent preemptive living-donor kidney transplantation obtained from his mother. Intraoperatively, we noted that dissection of the external iliac vessels was difficult because of dense adhesions. Arterial clamping was performed immediately below the bifurcation of the internal iliac artery to prevent further aortic dissection of the external iliac artery. After end-to-end anastomosis to the internal iliac artery was completed and the vascular clamp was released, the kidney began to produce urine immediately. CONCLUSION: This case suggests that kidney transplantation in patients undergoing endovascular aortic repair for aortic dissection can be performed by adequately applying a vascular clamp proximal to the internal iliac artery during vascular anastomosis.

A regressed germ cell tumor discovered secondary to azoospermia.

Introduction: Regressed germ cell tumors are a rare disease commonly diagnosed with metastatic symptoms without local symptoms in the testis. Case presentation: A 33-year-old man with azoospermia was referred to our hospital. His right testis was slightly swollen, and ultrasonography revealed hypoechogenicity of the right testis with decreased blood flow. Right high orchiectomy was performed. Pathologically, the seminiferous tubules were absent or highly atrophied with vitrification degeneration; however, no neoplastic lesion was confirmed. One-month post-surgery, the patient noticed a mass in the left supraclavicular fossa, of which a biopsy revealed seminoma. The patient was diagnosed with a regressed germ cell tumor and underwent systemic chemotherapy. Conclusion: We reported the first case of a regressed germ cell tumor discovered due to complaints of azoospermia.

A Clinical Study of Alveolar Bone Tissue Engineering Using Autologous Bone Marrow Stromal Cells: Effect of Optimized Cell-Processing Protocol on Efficacy.

(1) Objectives: The effect of cell-processing protocols on the clinical efficacy of bone tissue engineering is not well-known. To maximize efficacy, we optimized the cell-processing protocol for bone-marrow-derived mesenchymal stromal cells for bone tissue engineering. In this study, the efficacy of bone tissue engineering using this modified protocol was compared to that of the original protocol. (2) Materials and Methods: This single-arm clinical study included 15 patients. Cells were obtained from bone marrow aspirates and expanded in culture flasks containing basic fibroblast growth factor. The cells were seeded onto ß-tricalcium phosphate granules and induced into osteogenic cells for two weeks. Then, the cell-scaffold composites were transplanted into patients with severe atrophic alveolar bone. Radiographic evaluations and bone biopsies were performed. The results were compared with those of a previous clinical study that used the original protocol. (3) Results: Panoramic X-ray and computed tomography showed bone regeneration at the transplantation site in all cases. The average bone area in the biopsy samples at 4 months was 44.0%, which was comparable to that in a previous clinical study at 6 months (41.9%) but with much less deviation. No side effects related to cell transplantation were observed. In regenerated bone, 100% of the implants were integrated. (4) Conclusions: Compared to the original protocol, the non-inferiority of this protocol was proven. The introduction of an optimized cell-processing protocol resulted in a comparable quality of regenerated bone, with less fluctuation. Optimized cell-processing protocols may contribute to stable bone regeneration.

Role of Early Serial Renal Transplant Allograft Protocol Biopsies in Living Kidney Transplantations.

PURPOSE: This study aimed to analyze the incidence of subclinical rejection (SCR) in kidney transplantation patients and risk factors associated with SCR. METHODS: We assessed 80 protocol biopsies taken within 2 years postoperatively in 41 adult patients who underwent living donor kidney transplantation between 2017 and 2020. All patients were on immunosuppressant therapy that included tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The prevalence of Banff Borderline classification at 3, 6, and 12 months after transplantation was 4%, 5%, and 8 %, respectively, whereas none of the biopsies met the Banff criteria for acute T cell-mediated rejection throughout the study period. Active antibody-mediated rejection (ABMR) was only present in 8% of patients at 3 months after transplantation and chronic active ABMR at 6, 12, and 24 months after transplantation was detected in 10%, 13%, and 11% of the patients, respectively. Subgroup analysis revealed that 50% of the 6 patients with preformed anti-donor specific antibodies (DSAs) developed clinical or subclinical active ABMR within 3 months after transplantation, followed by chronic active ABMR according to serial histologic assessment. Conversely, only a small proportion of patients (3%) without preformed DSAs exhibited clinically active ABMR. CONCLUSIONS: SCR occurs too infrequently in patients with low immunologic risk and strong contemporary immunosuppression therapy to justify the diagnostic effort of serial protocol biopsies. However, protocol biopsies remain an indispensable tool in renal transplant monitoring and may be especially important in immunologically high-risk patients with pre-existing DSAs.

Anaplastic Transformation of Follicular Thyroid Carcinoma in Pulmonary Metastasis With Gradually Progressive Intra-tumoral Cavitation: A Case Report.

Anaplastic transformation of differentiated thyroid cancer is rare but clinically important because of the dismal prognosis after anaplastic transformation. Therefore, cases and findings of anaplastic transformation must be accumulated, which could ultimately lead to an earlier diagnosis and an improved prognosis. Here, we present a case of anaplastic transformation of follicular thyroid carcinoma (FTC) in a pulmonary metastatic lesion associated with gradually progressive tumor cavitation. The patient with FTC was diagnosed with multiple lung metastases three years after surgery for the primary tumor and metastatic neck lymph nodes. Annual treatment with radioactive iodine resulted in disease stability for 10 years. However, one lung metastasis in the left lower lobe gradually enlarged and was associated with intra-tumoral cavitation. The growing lung nodule was resected and pathologically diagnosed as an anaplastic transformation of FTC. Fourteen months after diagnosis, the patient died of pneumothorax caused by pleural dissemination despite multiple treatment interventions. This case highlights pulmonary metastasis with progressive cavitary lesions as a potential early sign of the anaplastic transformation of differentiated thyroid cancer.

Comparison between planar and single-photon computed tomography images for radiation intensity quantification in iodine-131 scintigraphy.

This study aimed to evaluate the feasibility of quantifying iodine-131 (131I) accumulation in scintigraphy images and compare planar and single-photon emission computed tomography (SPECT) images to estimate 131I radioactivity in patients receiving radioactive iodine therapy for thyroid cancer. We evaluated 72 sets of planar and SPECT images acquired between February 2017 and December 2018. Simultaneously, we placed a reference 131I capsule next to the patient during image acquisition. We evaluated the correlation between the intensity of the capsule in the images and the capsule dose and estimated the radiation dose at the thyroid bed. The mean capsule dose was 2.14 MBq (range, 0.63-4.31 MBq). The correlation coefficients (p-value) between capsule dose and maximum and mean intensities in both planar and SPECT images were 0.93 (p < 0.01), 0.96 (p < 0.01), 0.60 (p < 0.01), and 0.47 (p < 0.01), respectively. The mean intensities of planar images show the highest correlation coefficients. Based on a regression equation, the average radiation dose in the thyroid bed was 5.9 MBq. In conclusion, planar images reflected the radiation dose more accurately than SPECT images. The regression equation allows to determine the dose in other regions, such as the thyroid bed or sites of distant metastasis.

Clinical Outcome and 8-Year Follow-Up of Alveolar Bone Tissue Engineering for Severely Atrophic Alveolar Bone Using Autologous Bone Marrow Stromal Cells with Platelet-Rich Plasma and ß-Tricalcium Phosphate Granules.

BACKGROUND: Although bone tissue engineering for dentistry has been studied for many years, the clinical outcome for severe cases has not been established. Furthermore, there are limited numbers of studies that include long-term follow-up. In this study, the safety and efficacy of bone tissue engineering for patients with a severely atrophic alveolar bone were examined using autogenous bone marrow stromal cells (BMSCs), and the long-term stability was also evaluated. METHODS: BMSCs from iliac bone marrow aspirate were cultured and expanded. Then, induced osteogenic cells were transplanted with autogenous platelet-rich plasma (PRP) and ß-tricalcium phosphate granules (ß-TCP) for maxillary sinus floor and alveolar ridge augmentation. Eight patients (two males and six females) with an average age of 54.2 years underwent cell transplantation. Safety was assessed by monitoring adverse events. Radiographic evaluation and bone biopsies were performed to evaluate the regenerated bone. RESULTS: The major population of transplanted BMSCs belonged to the fraction of CD34-, CD45dim, and CD73+ cells, which was only 0.065% of the total bone marrow cells. Significant deviations were observed in cell growth and alkaline phosphatase activities among individuals. However, bone regeneration was observed in all patients and the average bone area in the biopsy samples was 41.9% 6 months following transplantation, although there were also significant deviations among each case. No adverse events related to the transplants were observed. In the regenerated bone, 27 out of 29 dental implants were integrated. Dental implants and regenerated bone were stable for an average follow-up period of 7 years and 10 months. CONCLUSIONS: Although individual variations were observed, the results showed that bone tissue engineering using BMSCs with PRP and ß-TCP was feasible for patients with severe atrophic maxilla throughout a long-term follow-up period and was considered safe. However, further studies with a larger number of cases and controls to confirm the efficacy of BMSCs and the development of a protocol to establish a reproducible quality of stem cell-based graft material will be required.

Pharmacological inhibition of sodium-calcium exchange activates NADPH oxidase and induces infection-independent NETotic cell death.

In addition to its function of innate immunity against invading pathogens, neutrophil extracellular traps (NETs) promote thrombosis, autoimmune disease, and cancer metastasis; therefore, unnecessary exposure to the triggers of infection-independent NET generation should be avoided. We herein show that inhibition of forward-mode Na+/Ca2+ exchange by amiloride analogs, 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and 5-(N-Methyl-N-isobutyl)amiloride (MIA), triggers NETotic cell death independently of infectious stimuli. Isolated human neutrophils treated with EIPA and MIA undergo NETotic cell death by an increase of intracellular Ca2+ following activation of NADPH oxidase and the resultant upregulation of intracellular ROS. EIPA- and MIA-mediated intracellular Ca2+ increase is attributed to the competitive binding of EIPA and MIA against Na+ to Na+/Ca2+ exchanger 1 (NCX1). These results demonstrate a new mechanism of infection-independent NET generation and implicate NCX1 as a physiologic regulator of intracellular calcium balance and NETotic cell death.

Comparison of thyroid hormone withdrawal and recombinant human thyroid-stimulating hormone administration for adjuvant therapy in patients with intermediate- to high-risk differentiated thyroid cancer.

OBJECTIVE: To compare the clinical outcome in patients who received adjuvant therapy with radioactive iodine (RAI) using different preparation methods, namely, thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH), after undergoing thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma (DTC) according to the American Thyroid Association criteria. METHODS: Between May 2012 and October 2018, 136 patients who underwent adjuvant therapy with high-dose (3700 MBq) RAI for DTC without any metastatic lesions or macroscopic residual lesions after surgical resection were retrospectively selected. Patients were excluded if distant metastasis was confirmed during adjuvant therapy or if the outcome could not be confirmed; thus, 112 patients were finally evaluated. Patients underwent either a 3-week I restriction with thyroxine withdrawal or a 2-week I restriction with rhTSH administration. The serum thyroglobulin (Tg) concentration was measured, and 131I scintigraphy (370 MBq) was performed 6-12 months after adjuvant therapy. The definition of the initial achievement of adjuvant therapy was the disappearance of the uptake of 131I at the thyroid bed and serum Tg concentration < 2.0 ng/mL. The results of the adjuvant therapy between the groups were compared using the Fisher's exact test, and the TSH levels and estimated glomerular filtration rate (eGFR) were compared using the Welch's t test. RESULTS: The THW and rhTSH groups included 47 and 65 patients, respectively, and the intermediate- and high-risk groups included 63 and 49 patients, respectively. No patient was assigned to the low-risk group. In the THW and rhTSH groups, the initial RAI adjuvant therapy goal was achieved in 30/47 (63.8%) and 46/65 patients (70.8%), respectively (p = 0.54); mean ± standard deviation of the TSH levels was 123.8 ± 46.4 µIU/mL and 274.5 ± 97.7 µIU/mL, respectively (p < 0.01), and eGFR (treatment/pre-treatment) was 0.81 and 0.99, respectively (p < 0.01). In the intermediate- and high-risk groups, the initial RAI adjuvant therapy goal was achieved in 43/63 patients (68.3%) and 33/49 (67.3%), respectively (p = 1.0). CONCLUSION: No significant differences were observed between the preparation methods in the initial achievement of RAI adjuvant therapy. However, patients in the rhTSH group demonstrated higher TSH levels and retained eGFR.

Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis.

Neutrophil extracellular traps (NETs) promote cancer metastasis in preclinical models following massive exogenous inflammatory stimuli. It remains unknown whether cancer hosts under physiologic conditions experience NETosis and consequent metastasis. Here we show that plasma redox imbalance caused by albumin oxidation promotes inflammation-independent NETosis. Albumin is the major source of free thiol that maintains redox balance. Oxidation of albumin-derived free thiol is sufficient to trigger NETosis via accumulation of reactive oxygen species within neutrophils. The resultant NETs are found predominantly within lungs where they contribute to the colonization of circulating tumor cells leading to pulmonary metastases. These effects are abrogated by pharmacologic inhibition of NET formation. Moreover, albumin oxidation is associated with pulmonary metastasis in a cohort of head and neck cancer patients. These results implicate plasma redox balance as an endogenous and physiologic regulator of NETosis and pulmonary cancer metastasis, providing new therapeutic and diagnostic opportunities for combatting cancer progression.

Dosimetric advantages afforded by a new irradiation technique, Dynamic WaveArc, used for accelerated partial breast irradiation.

PURPOSE: To identify dosimetric advantages of the novel Dynamic WaveArc (DWA) technique for accelerated partial breast irradiation (APBI), compared with non-coplanar three-dimensional conformal radiotherapy (nc3D-CRT) and coplanar tangential volumetric modulated arc therapy (tVMAT) with dual arcs of 45-65°. METHODS: Vero4DRT enables DWA by continuous gantry rotation and O-ring skewing with movement of the multi-leaf collimator. We compared the dose distributions of DWA, nc3D-CRT and tVMAT in 24 consecutive left-sided breast cancer patients treated with APBI (38.5 Gy in 10 fractions). The average doses and volumes to the planning target volume (PTV) and organs at risk, especially heart and left anterior descending artery (LAD) were compared among DWA, nc3D-CRT and tVMAT. RESULTS: The doses and volumes to the PTVs did not differ significantly among the three plans. For the DWA plans, the mean dose to the heart was 0.2 ±â€¯0.1 Gy, less than those of the nc3D-CRT and tVMAT plans. The D2% values of the planning organ at risk volume of the LAD were 9.3 ±â€¯10.9%, 28.2 ±â€¯31.9% and 20.3 ±â€¯25.7% for DWA, nc3D-CRT and tVMAT, respectively. The V20Gy and V10Gy of the ipsilateral lung for the DWA plans were also significantly lower. CONCLUSIONS: DWA allowed to find a better compromise for OAR which overlapped with the PTV. Use of the DWA for APBI improved the dose distributions compared with those of nc3D-CRT and tVMAT.

Three-dimensional intrafractional internal target motions in accelerated partial breast irradiation using three-dimensional conformal external beam radiotherapy.

PURPOSE: We evaluated three-dimensional intrafractional target motion, divided into respiratory-induced motion and baseline drift, in accelerated partial breast irradiation (APBI). METHODS: Paired fluoroscopic images were acquired simultaneously using orthogonal kV X-ray imaging systems at pre- and post-treatment for 23 patients who underwent APBI with external beam radiotherapy. The internal target motion was calculated from the surgical clips placed around the tumour cavity. RESULTS: The peak-to-peak respiratory-induced motions ranged from 0.6 to 1.5mm in all directions. A systematic baseline drift of 1.5mm towards the posterior direction and a random baseline drift of 0.3mm in the lateral-medial and cranial-caudal directions were observed. The baseline for an outer tumour cavity drifted towards the lateral and posterior directions, and that for an upper tumour cavity drifted towards the cranial direction. Moderate correlations were observed between the posterior baseline drift and the patients' physical characteristics. The posterior margin for intrafractional uncertainties was larger than 5mm in patients with greater fat thickness due to the baseline drift. CONCLUSIONS: The magnitude of the intrafractional motion was not uniform according to the direction, patients' physical characteristics, or tumour cavity location due to the baseline drift. Therefore, the intrafractional systematic movement should be properly managed.