Optimal combination of collimator angles for dual-arc volumetric modulated arc therapy planning in stereotactic body radiotherapy for spinal metastases.

In planning the treatment of spinal metastases using stereotactic body radiotherapy (SBRT), the optimal blocking of the spinal cord to match the leaf travel can be achieved with a first-arc collimator angle of approximately 90°. We aim to clarify the optimal second-arc collimator angles when the first-arc collimator angle is fixed to 90° in dual-arc volumetric modulated arc therapy (VMAT). For this retrospective study, we considered 37 spinal segments with spinal metastases and created dual-arc VMAT plans. In the plans, 24 Gy in 2 fractions were prescribed, and the first-arc collimator angle was fixed to 90° while varying the second-arc collimator angle in increments of 15° from 0° to 90°. All the plans were normalized such that the planning organ-at-risk volume for the spinal cord D0.035 cc = 17 Gy and satisfied other dose constraints. D95% for the planning target volume (PTV), V100% for the overlap between the PTV and 10 mm expansion of the spinal cord, modified gradient index, monitor unit, and 3%/1 mm gamma passing rates were compared between different second-arc collimator angles using the Wilcoxon signed-rank test and Bonferroni correction. PTV D95% and overlap V100% were the highest for a second-arc collimator angle of 45° and decreased as the angle approached either 0° or 90°. The maximum mean differences of PTV D95% and overlap V100% were -2.66% (90° vs 45°, p < 0.0024) and -5.49% (90° vs 45°, p < 0.0024), respectively. Moreover, the second-arc collimator angle of 45° was the least suitable in terms of the modified gradient index. The required monitor unit increased from the second-arc collimator angle of 15° to 45°, and the 3%/1 mm gamma passing rates reached over 95% for the evaluated second-arc collimator angles of 15°, 30°, and 45°. We found that in the dual-arc VMAT plan for spine SBRT, second-arc collimator angles other than 90° were suitable, and 45° was the optimal angle in terms of target coverage including the area around the spinal cord.

Subcutaneous Sweet's Syndrome Presenting With a Single Cutaneous Lesion on the Thigh.

Sweet's syndrome (SS), also known as acute febrile neutrophilic dermatosis, manifests as tender, erythematous skin lesions such as papules, nodules, and plaques that may appear vesicular or pustular. The condition is characterized by widespread infiltrates mainly consisting of mature neutrophils, usually in the upper dermis. Erythema nodosum (EN) is a form of septal panniculitis marked by tender, erythematous lesions primarily appearing on the lower legs. Additionally, subcutaneous Sweet's syndrome (SSS) is a rare variant of SS that mainly involves the subcutaneous adipose tissue. Skin lesions in SSS generally present as tender, erythematous subepidermal nodules on the extremities, morphologically resembling EN. Both EN and SS can present with fever, malaise, gastrointestinal disturbances, lymphadenopathy, arthralgia, increased white blood cell (WBC) count with neutrophilia, elevated C-reactive protein (CRP), and elevated erythrocyte sedimentation rate (ESR), making differentiation between them often challenging. Therefore, histopathologic evaluation is necessary for an accurate diagnosis. In our case, the patient exhibited a very painful plaque measuring 20 cm in diameter on the upper thigh without significant neutrophil infiltration in the dermis, but with subcutaneous septal neutrophil infiltration. Generally, SS shows stronger leukocytosis with neutrophilia than EN does. Considering the clinical symptoms, laboratory results, and clinical progression, the clinicopathological findings aligned more closely with SSS than EN. This article describes a rare case of SSS presenting with a single cutaneous lesion on the thigh, which mimicked the histopathological features of EN.

Insulinoma presenting with anti-insulin antibodies.

Summary: An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies. Learning points: Insulinoma presenting with concomitant anti-insulin antibodies appears rare. Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome. Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

A Single-center Pilot Study on the Efficacy and Safety of Acetic Acid-enhanced Magnifying Endoscopy with Narrow-Band Imaging for Diagnosis of Colorectal Epithelial Neoplasms.

BACKGROUND AND AIMS: We investigated the ideal acetic acid (AA) concentration for AA-enhanced, narrow-band imaging (NBI) magnifying endoscopy (ANBI-ME) in the diagnosis of superficial colorectal neoplasms and evaluated its clinical efficacy. METHODS: During the exploratory phase, we investigated four concentrations (1.5%, 2.25%, 3.0%, and 4.5%) in rotation by performing ANBI-ME on 50 superficial colorectal neoplasms at each concentration. A favorable AA concentration was determined by evaluating the diagnostic accuracy, AA whitening duration (AD), peristalsis, and bleeding following endoscopic resection. In the validation phase, we assessed inter-observer agreements for ANBI-ME with the determined AA concentration and inter-methodological agreements between that and subsequently conducted crystal violet-stained magnifying endoscopy (CV-ME) with the exploratory set and 98 additional patients. RESULTS: The diagnostic accuracies were 89.3% (42/47) for 1.5% AA, 92.0% (46/50) for 2.25%, 96.8% (61/63) for 3.0%, and 97.8% (46/47) for 4.5% with no significant difference (p = 0.26). A significant positive correlation was observed between the AA concentrations and ADs (p < 0.001). No significant differences in hyperperistalsis or post-resection bleeding were observed. The optimal AA concentration was determined to be 4.5%. In the validation analysis, the accuracy rates were 72.4% (105/145) using AMBI-ME and 68.3% (99/145) using CV-ME (p = 0.43). Strong agreements were noted between two observers (κ, 0.87 for ANBI-ME; 0.83 for CV-ME) and between the methods (κ, 0.87 and 0.81 for each observer). CONCLUSION: For diagnosing colorectal lesions, an AA concentration of 4.5% in ANBI-ME was safe and effective. Its diagnostic performance was comparable to CV-ME, and future large-sample studies may confirm its potential as a reliable alternative endoscopic diagnostic method.

Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor.

Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/ß = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

Relationship between frailty and locomotive syndrome in older patients with degenerative cervical myelopathy: A retrospective longitudinal study.

BACKGROUND: The management of degenerative cervical myelopathy (DCM), which often impairs lower extremity function and increases the risk of falls, is gaining recognition for its importance in an aging society. Despite the significant overlap between frailty and locomotive syndrome (LS) in older adults, their interaction in older DCM patients remains unclear. We aimed to determine the characteristics of older DCM patients with frailty, focusing on the association between frailty and LS. METHODS: We retrospectively examined the clinical records and imaging data of consecutive patients aged 65 years and above who underwent surgery for DCM at a single facility. Frailty and LS stage were diagnosed using the modified frailty index-11 and the 25-question Geriatric Locomotive Function Scale (GLFS-25), respectively. RESULTS: A total of 114 subjects were analyzed, among whom approximately 30% were diagnosed with frailty. DCM patients with frailty had significantly worse Japanese Orthopaedic Association Cervical Myelopathy Assessment Questionnaire (JOACMEQ) and GLFS-25 scores at baseline than did those without frailty. Moreover, DCM patients with frailty had significantly more advanced LS stage at baseline than did those without frailty. Meanwhile, no significant difference in the improvement in JOACMEQ and GLFS-25 scores were observed between those with and without frailty after surgery. More precisely, DCM patients with frailty experienced better improvement in lower extremity function based on the JOACMEQ than did those without frailty. CONCLUSIONS: Our results demonstrated that older DCM patients had favorable outcomes following surgery regardless of frailty. Despite the significant association between frailty and LS in DCM patients, frailty did not negatively impact the improvement in LS in older DCM patients. These findings provide valuable information for both older DCM patients and their attending physicians that would help guide decisions about cervical spine surgery for DCM.

A case of olfactory ganglioneuroblastoma in a dog: immunohistochemical comparison with olfactory neuroepithelia and olfactory neuroblastomas.

In the present study, histopathological and immunohistochemical findings of olfactory ganglioneuroblastoma in a dog were compared to those of canine olfactory neuroepithelia and neuroblastomas. Olfactory ganglioneuroblastoma consists of ganglion cell-like tumor cells with Schwannian stroma and neuroblast-like tumor cells. Immunohistochemically, ganglion cell-like tumor cells were immunopositive for synaptophysin, ß3-tubulin, and tyrosine hydroxylase, Schwannian stroma was immunopositive for GFAP and SOX2, and neuroblast-like tumor cells were immunopositive for OLIG2, ß3-tubulin, SOX2, cytokeratin AE1/AE3, and p63. The immunohistochemical results of olfactory neuroepithelia and olfactory neuroblastomas were similar to those of neuroblast-like tumor cells. These results suggest that the ganglion cell-like tumor cells in the present case have a sympathetic neuron immunophenotype, whereas neuroblast-like tumor cells have an olfactory neuroepithelial immunophenotype.

Phase II Clinical Trial of Second Course of Stereotactic Body Radiotherapy for Spinal Metastases.

PURPOSE: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. METHODS: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. RESULTS: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6-51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1-2 and S1-5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. CONCLUSIONS: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.

Routine screening serum tests to detect underlying thyroid and autoimmune diseases in patients with moyamoya disease.

BACKGROUND: Recent studies have revealed that thyroid and autoimmune diseases may be associated with sporadic moyamoya disease. However, whether routine screening serum tests to detect these underlying diseases are useful or not remains unclear. METHODS: We retrospectively evaluated 459 patients with moyamoya disease but without previous history of thyroid or autoimmune diseases who underwent the screening serum tests targeting thyroid and autoimmune diseases from 2016 to 2023 in our institute. The number of patients who were diagnosed as thyroid or autoimmune diseases after these tests were investigated. RESULTS: Among the patients who were screened, 237 (42.6 %) patients had abnormal results for some factors, such as thyroid hormones or autoantibodies. After consultation with endocrinologists or rheumatologists, 27 (5.9 %) patients were newly diagnosed with thyroid diseases, including six (1.3 %) patients with Graves' disease, 19 (4.1 %) patients with Hashimoto thyroiditis and two (0.4 %) patients with other thyroid diseases; however, none of the patients were diagnosed with nonthyroidal autoimmune diseases, such as Sjogren's syndrome, antiphospholipid syndrome, or rheumatoid arthritis, listed as moyamoya-related diseases and targeted by our screening serum tests. Patients with newly diagnosed underlying diseases were more likely to be female compared to patients without new diagnosis (96.3 % vs. 72.2 %, p = 0.03). CONCLUSION: Routine thyroid-related serum screening may be clinically meaningful in patients with moyamoya disease to detect occult thyroid diseases, especially in female patients. However, routine serum screening tests targeting other autoimmune diseases are not recommended unless the patients have equivalent symptoms.

Predictors of Patient Dissatisfaction after Lumbar Spinal Canal Stenosis Surgery: A Multicenter Retrospective Study.

Introduction: Recently, patient satisfaction has gained prominence as a crucial measure for ensuring patient-centered care. Furthermore, patient satisfaction after lumbar spinal canal stenosis (LCS) surgery is an important metric for physician's decision of surgical indication and informed consent to patient. This study aimed to elucidate how patient satisfaction changed after LCS surgery to identify factors that predict patient dissatisfaction. Methods: We retrospectively reviewed time-course data of patients aged ≥40 years who underwent LCS surgery at multiple hospitals. The participants completed the Zurich Claudication Questionnaire (ZCQ) and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) before surgery and then 6 months and 1 year postsurgery. Patient satisfaction was categorized according to the postoperative score of the satisfaction domain of the ZCQ: satisfied, score ≤2.0; moderately satisfied, 2.0< score ≤2.5; and dissatisfied, score >2.5. Results: The study enrolled 241 patients. Our data indicated a satisfaction rate of around 70% at 6 months and then again 1 year after LCS surgery. Among those who were dissatisfied 6 months after LCS surgery, 47.6% were more satisfied 1 year postsurgery. Furthermore, 86.2% of those who were satisfied 6 months after LCS surgery remained satisfied at 1 year. Multivariable analysis revealed that age (relative risk, 0.5; 95% confidence interval, 0.2-0.8) and preoperative score of psychological disorders on the JOABPEQ (relative risk, 0.2; 95% confidence interval, 0.03-0.08) were significantly associated with LCS surgery dissatisfaction. In addition, the receiver operating characteristic curve analysis revealed that the cutoff value for the preoperative score of psychological disorder of the JOABPEQ was estimated at 40 for LCS surgery dissatisfaction. Conclusions: Age and psychological disorders were identified as significant predictors of dissatisfaction, with a JOABPEQ cutoff value providing potential clinical applicability.

Assessment of Surgical Outcomes in Patients with Degenerative Cervical Myelopathy Using the 25-Question Geriatric Locomotive Function Scale: A Longitudinal Observational Study.

Introduction: Locomotive syndrome caused by degenerative musculoskeletal diseases is reported to improve with surgical treatment. However, it is unclear whether surgical treatment is effective for the locomotive syndrome developing in patients with degenerative cervical myelopathy (DCM). Thus, this study primarily aimed to longitudinally assess the change in locomotive syndrome stage before and after cervical spinal surgery for patients with DCM using the 25-question geriatric locomotive function scale (GLFS-25). A secondary objective was to identify factors associated with the postoperative improvement in the locomotive syndrome stage. Methods: We retrospectively reviewed clinical data of patients undergoing cervical spine surgery at our institution from April 2020 to May 2022 who had answered the Japanese Orthopaedic Association Cervical Myelopathy Assessment Questionnaire, visual analog scale, and GLFS-25 preoperatively and at 6 months and 1 year postoperatively. We collected demographic data, medical history, preoperative radiographic parameters, presence or absence of posterior longitudinal ligament ossification, and surgical data. Results: We enrolled 115 patients (78 men and 37 women) in the present study. Preoperatively, using the GLFS-25, 73.9% of patients had stage 3, 10.4% had stage 2, 9.6% had stage 1, 6.1% had no locomotive syndrome. The stage distribution of locomotive syndrome improved significantly at 6-months and 1-year postoperatively. The multivariable Poisson regression analysis revealed that better preoperative lower extremity function (relative risk: 3.0; 95% confidence interval: 1.01-8.8) was significantly associated with postoperative improvement in the locomotive syndrome stage. Conclusions: This is the first study to longitudinally assess the locomotive syndrome stage in patients with DCM using GLFS-25. Our results indicated that patients with DCM experienced significant improvement in the locomotive syndrome stage following cervical spine surgery. Particularly, the preoperative lower extremity function was significant in postoperative improvement in the locomotive syndrome stage.

Stenting for subclavian steal phenomenon to restore cerebral perfusion due to acute carotid occlusion following carotid endarterectomy: a case report.

BACKGROUND: Perioperative symptomatic carotid artery occlusion after carotid endarterectomy is a rare complication. In this study, we present a case of symptomatic acute carotid artery occlusion that occurred after carotid endarterectomy in a patient with coexistent subclavian artery steal phenomenon, which was successfully treated with subclavian artery stenting. CASE PRESENTATION: A 57-year-old East Asian female presented with stenosis in the left common carotid artery and left subclavian artery along with subclavian steal. The proximal segment of the left anterior cerebral artery was hypoplastic, and the posterior communicating arteries on both sides were well-developed. Left internal carotid artery stenosis progressed during the follow-up examination; therefore, left carotid endarterectomy was performed. On the following day, symptoms of cerebral perfusion deficiency appeared due to occlusion of the left carotid artery. The stenotic origin of the left common carotid artery and the suspected massive thrombus in the left carotid artery posed challenges to carotid revascularization. Therefore, left subclavian artery stenting for the subclavian steal phenomenon was determined to be the best option for restoring cerebral blood flow to the whole brain. Her symptoms improved after the procedure, and the postprocedural workup revealed improved cerebral blood flow. CONCLUSION: Subclavian artery stenting is safe and may be helpful in patients with cerebral perfusion deficiency caused by intractable acute carotid occlusion coexisting with the subclavian steal phenomenon. Revascularization of asymptomatic subclavian artery stenosis is generally not recommended. However, cerebral circulatory insufficiency as a comorbidity may be worth considering.

Prophylactic endoscopic transpapillary gallbladder stenting to prevent acute cholecystitis induced after metallic stent placement for malignant biliary strictures: a retrospective study, Japan.

Background/Aims: Endoscopic biliary drainage using self-expandable metallic stents (SEMSs) for malignant biliary strictures occasionally induces acute cholecystitis (AC). This study evaluated the efficacy of prophylactic gallbladder stents (GBS) during SEMS placement. Methods: Among 158 patients who underwent SEMS placement for malignant biliary strictures between January 2018 and March 2023, 30 patients who attempted to undergo prophylactic GBS placement before SEMS placement were included. Results: Technical success was achieved in 21 cases (70.0%). The mean diameter of the cystic duct was more significant in the successful cases (6.5 mm vs. 3.7 mm, p<0.05). Adverse events occurred for 7 patients (23.3%: acute pancreatitis in 7; non-obstructive cholangitis in 1; perforation of the cystic duct in 1 with an overlap), all of which improved with conservative treatment. No patients developed AC when the GBS placement was successful, whereas 25 of the 128 patients (19.5%) without a prophylactic GBS developed AC during the median follow-up period of 357 days (p=0.043). In the multivariable analysis, GBS placement was a significant factor in preventing AC (hazard ratio, 0.61; 95% confidence interval, 0.37-0.99; p=0.045). Conclusions: GBS may contribute to the prevention of AC after SEMS placement for malignant biliary strictures.

The Impact of Frailty on Surgical Outcome of Patients with Lumbar Spinal Canal Stenosis.

Introduction: Frailty is an important factor in surgical outcomes. The current study aimed to evaluate the effect of preoperative frailty on postoperative outcomes in older patients with lumbar spinal canal stenosis (LSCS). Methods: We retrospectively examined 209 patients aged ≥65 years who underwent surgery for LSCS. Health-related quality-of-life (HRQOL) tools, including the Roland-Morris Disability Questionnaire (RDQ), Zurich Claudication Questionnaire (ZCQ), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), were used in the assessment conducted before surgery and at 6 months and 1 year after surgery. Frailty was categorized based on the 11-item modified frailty index (mFI-11). Patients with mFI-11 of 0, <0.21, and >0.21 were classified under the robust (R), pre-frailty (P), and frailty (F) groups, respectively. Results: According to the mFI-11, 24, 138, and 47 patients were included in the R, P, and F groups, respectively. Regarding preoperative radiographic parameters, there was a remarkable increase in the sagittal vertical axis and a significant decrease in the development of lumbar lordosis with frailty progression. The preoperative scores of RDQ and ZCQ, and lumbar function, walking ability, social life, and psychological disorder domain scores of JOABPEQ differed significantly among these groups. The frequency of revision surgery was not higher in the F group than in the other groups. After adjustment for factors have shown different distributions among the three groups, the frequency of effective surgical cases did not show a clear trend among the three groups in all domains of the JOABPEQ. Conclusions: The preoperative HRQOL scores and the radiographic parameters of patients with LSCS worsened with frailty severity. However, frailty did not affect the rate of revision surgery and surgical efficacy in patients with LSCS. Although this study has limitations, our findings indicated that even LSCS patients with frailty can be considered for surgery if they have an indication for LSCS surgery.

Phase I/II study of stereotactic body radiotherapy boost in patients with cervical cancer ineligible for intracavitary brachytherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost. MATERIALS AND METHODS: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival. RESULTS: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases. CONCLUSION: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer. STUDY REGISTRATION: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).

Clinicopathological importance of Bcl-2 and p53 in postmenopausal triple-negative breast carcinoma and association with age.

Appropriate biomarkers are required to predict the clinical outcome of triple-negative breast cancer (TNBC). In this study, we focused on the clinical importance of two representative tumor-associated proteins, Bcl-2 and p53. Bcl-2 expression is usually related to estrogen receptor expression and a favorable outcome in breast cancer. TNBC has been reported to show a high frequency of p53 positivity suggesting TP53 mutations. The expressions of Bcl-2 and p53 were immunohistochemically examined in TNBC involving two age groups of postmenopausal women (≥75 y/o, n = 75; 55-64 y/o, n = 47), who underwent surgery without neoadjuvant therapy. We examined their associations with each other, or with clinicopathological factors including the outcome. Bcl-2 expression was inversely correlated with androgen receptor, apocrine morphology, and p53 expressions, and was an independent predictor of a poor outcome in total or in younger women. p53 positivity was associated with a more favorable outcome than p53 negativity in the younger group. In combined analyzes, none of the twenty Bcl-2-negative/p53-positive cases in the younger group exhibited recurrence, resulting in the independent favorable predictive value of Bcl-2-negative/p53-positive. The anti-apoptotic nature of Bcl-2 may be apparent in TNBC. The excellent outcome of Bcl-2-negative/p53-positive cases in the younger group warrants further combined investigation of Bcl-2/p53 in TNBC.

Plain computed tomography for differentiating neoplastic and non-neoplastic pedunculated gallbladder polyps.

AIMS: Surgery is recommended for large pedunculated gallbladder polyps (PGPs), which measure 10 mm or more in size, because they tend to be neoplastic polyps (NPs), such as adenomas and adenocarcinomas. However, after resection, they are often found to be non-neoplastic polyps (non-NPs). This study aimed to evaluate the usefulness of plain CT in distinguishing NPs from non-NPs. METHODS: Of the 80 patients who underwent cholecystectomy for PGPs ( 10 mm between January 2008 and February 2021, 46 who underwent plain and contrast-enhanced CT (CE-CT) before resection were included in this study. We retrospectively assessed the polyp detection rate (PDR) using CT and calculated the difference in the CT values between PGPs and the surrounding bile. RESULTS: Twenty-one patients had NPs (12 adenomas, 5 carcinomas in adenoma, and 4 adenocarcinomas). The others were non-NPs (24 cholesterol polyps and one hyperplastic polyp). The PDR using plain CT was significantly higher in the NP group than in the non-NP group (38% (8/21) vs. 0% (0/25), p <0.01). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of NPs were 38%, 100%, 100%, 66%, and 72%, respectively. The difference in the CT values between PGPs and the surrounding bile was significantly larger in the NP group than in the non-NP group (14.12 ± 11.38 HU, 5.04 ± 6.15 HU, p <0.01). CONCLUSIONS: PGPs detected using plain CT had a high probability of being NPs. Plain CT is therefore considered to be useful for differentiating NPs from non-NPs.

Predicting potential target genes in molecular biology experiments using machine learning and multifaceted data sources.

Experimental analysis of functionally related genes is key to understanding biological phenomena. The selection of genes to study is a crucial and challenging step, as it requires extensive knowledge of the literature and diverse biomedical data resources. Although software tools that predict relationships between genes are available to accelerate this process, they do not directly incorporate experiment information derived from the literature. Here, we develop LEXAS, a target gene suggestion system for molecular biology experiments. LEXAS is based on machine learning models trained with diverse information sources, including 24 million experiment descriptions extracted from full-text articles in PubMed Central by using a deep-learning-based natural language processing model. By integrating the extracted experiment contexts with biomedical data sources, LEXAS suggests potential target genes for upcoming experiments, complementing existing tools like STRING, FunCoup, and GOSemSim. A simple web interface enables biologists to consider newly derived gene information while planning experiments.

Intradiscal administration of autologous platelet-rich plasma in patients with Modic type 1 associated low back pain: A prospective pilot study.

Background: Various treatments for chronic low back pain (LBP) have been reported; among them, platelet-rich plasma (PRP) as a regenerative medicine has attracted much attention. Although Modic type 1 change (MC1) is associated with LBP, no treatment has been established so far. In addition, no studies have administered PRP to intervertebral discs (IVDs) in patients with LBP, targeting MC1 only. Thus, the purpose of this study was to determine the safety and efficacy of PRP administration to the IVDs in patients with MC1 experiencing LBP. Methods: PRP was injected intradiscally to 10 patients with MC1 experiencing LBP. Patients were followed prospectively for up to 24 weeks after primary administration. Physical condition, laboratory data, and lumbar x-ray images were evaluated for safety assessment. Furthermore, to evaluate the effectiveness of PRP, patient-reported outcomes were considered. In addition, changes in MC1 were assessed using magnetic resonance imaging (MRI). Results: There were no adverse events in the laboratory data or lumbar X-ray images after administration. The mean visual analog scale, which was 70.0 ± 13.3 before the treatment, significantly decreased 1 week after PRP administration and was 39.0 ± 28.8 at the last observation. Oswestry disability index and Roland Morris disability questionnaire scores promptly improved after treatment, and both improved significantly 24 weeks after PRP administration. Follow-up MRI 24 weeks after treatment showed a significant decrease in the mean high-signal intensity of fat-suppressed T2-weighted imaging from 10.1 to 7.90 mm2 compared with that before PRP administration. Conclusions: The safety and efficacy of PRP administration to the IVDs of patients with MC1 experiencing LBP were identified. Post-treatment MRI suggested improvement in inflammation, speculating that PRP suppressed inflammation and consequently relieved the patient's symptoms. Despite the small number of patients, this treatment is promising for patients with MC1 experiencing LBP. The study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (Japan Registry of Clinical Trials [jRCT] No. jRCTb042210159).