Dietary melatonin and liver cancer incidence in Japan: From the Takayama study.

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.

KORTUC, a novel hydrogen peroxide­based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer.

Kochi Oxydol Radiation Therapy for Unresectable Carcinoma (KORTUC) is a novel radiosensitizer invented by Professor Ogawa at Kochi University (Japan) in 2006. The current study aimed to report the experience of the present authors with the use of KORTUC treatment in combination with interstitial brachytherapy (ISBT), with or without external beam (EB) radiotherapy (RT), in patients with locally recurrent cervical cancer (LRCC), who were likely to have a high risk of poor prognosis. Between April 2012 and January 2020, 14 female patients (15 tumoral lesions) with LRCC underwent KORTUC with ISBT. Their previous treatments included surgery (n=4), radiation therapy (n=8) and surgery plus RT (n=3). The primary lesions were located in the vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2) and lymph nodes (n=2). At 2 h before RT, KORTUC was injected intratumorally via direct colposcopy. The dose of KORTUC ranged from 4-12 ml, adjusted for the tumor size. For patients who underwent ISBT, KORTUC was administered before and after insertion of the applicator before irradiation. Intratumoral injection of KORTUC was completed without any technical or safety issues in all 15 patients; it was well tolerated with no adverse events observed. KORTUC also showed preferable efficacy; a clinical complete response was observed in 87% of patients and the initial response rate was 100%. The 2-year local control rate in patients who underwent ISBT + KORTUC was 79%, whereas it was 63% in the re-irradiation group which was significantly lower (P=0.02) than that in the non-irradiation group (100%). Based on this finding, KORTUC with external irradiation is considered to be an optimal treatment strategy for patients with newly diagnosed LRCC this disease. Additionally, KORTUC may be an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Surgical Management of Breast Cancer Developing Along the Pathway of a Ventriculoperitoneal Shunt: A Case Report.

BACKGROUND Ventriculoperitoneal shunts are commonly used in neurosurgery for the treatment of hydrocephalus. This case report details an unusual instance where breast cancer developed along the pathway of an existing ventriculoperitoneal shunt. CASE REPORT An 86-year-old woman, who previously underwent ventriculoperitoneal shunt placement for normal-pressure hydrocephalus, visited our hospital upon detecting a mass in her left breast. The physical examination discovered an irregular mass located at the 9 o'clock position of the left breast. Subsequent breast ultrasonography identified a 36 mm mass with indistinct borders, rough margins, and signs of skin infiltration. Invasive ductal carcinoma of a triple-negative subtype was diagnosed through a core-needle biopsy. Contrast-enhanced computed tomography indicated the ventriculoperitoneal shunt's pathway, running from the left ventricle, passing through the center of the breast mass, and leading into the abdominal cavity. Fears of shunt occlusion and potential infection due to the untreated breast cancer prompted surgical intervention after consultation with the neurosurgeon. The surgery involved rerouting the ventriculoperitoneal shunt from the left thoracoabdomen to the right, performing a left mastectomy, and removing the fistula in the abdominal wall to minimize the risk of cancer recurrence along the shunt pathway. Postoperative histopathological examination confirmed the initial diagnosis of invasive ductal carcinoma of a triple-negative subtype, with no malignancy detected in the removed abdominal wall fistula. CONCLUSIONS Taking into account prior cases of cancer metastasizing distantly due to ventriculoperitoneal shunts, our case emphasizes the necessity to consider additional preventative measures against cancer seeding. This approach is particularly significant when treating breast cancer that arises along the pathway of a ventriculoperitoneal shunt, apart from performing conventional breast cancer surgery.

Analysis of spontaneous speech in Parkinson's disease by natural language processing.

INTRODUCTION: Patients with Parkinson's disease (PD) encounter a variety of speech-related problems, including dysarthria and language disorders. To elucidate the pathophysiological mechanisms for linguistic alteration in PD, we compared the utterance of patients and that of healthy controls (HC) using automated morphological analysis tools. METHODS: We enrolled 53 PD patients with normal cognitive function and 53 HC, and assessed their spontaneous speech using natural language processing. Machine learning algorithms were used to identify the characteristics of spontaneous conversation in each group. Thirty-seven features focused on part-of-speech and syntactic complexity were used in this analysis. A support-vector machine (SVM) model was trained with ten-fold cross-validation. RESULTS: PD patients were found to speak less morphemes on one sentence than the HC group. Compared to HC, the speech of PD patients had a higher rate of verbs, case particles (dispersion), and verb utterances, and a lower rate of common noun utterances, proper noun utterances, and filler utterances. Using these conversational changes, the respective discrimination rates for PD or HC were more than 80%. CONCLUSIONS: Our results demonstrate the potential of natural language processing for linguistic analysis and diagnosis of PD.

Clinico-imaging features of subjects at risk of Lewy body disease in NaT-PROBE baseline analysis.

Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients with Parkinson's disease and dementia with Lewy bodies. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥2 prodromal symptoms (dysautonomia, hyposmia, and probable RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study.

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site-specific cancers in a population-based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE Nε -carboxymethyl-lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries. During a mean follow-up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92-3.10), 1.48 (95% CI: 0.77-2.84), and 2.10 (95% CI: 1.10-3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study.

Design of a MOF based on octa-nuclear zinc clusters realizing both thermal stability and structural flexibility.

An octa-nuclear zinc (Zn8) cluster-based two-fold interpenetrated metal-organic framework (MOF) of [(CH3)2NH2]2[Zn8O3(FDC)6]·7DMF (denoted as Zn8-as; H2FDC = 9H-fluorene-2,7-dicarboxylic acid; DMF = N,N-dimethylformamide) was synthesized by the reaction of a hard base of a curved dicarboxylate ligand (H2FDC) with the borderline acid of Zn(II) under solvothermal conditions. Zn8-as shows significant crystal volume shrinkage upon heating, yielding a solvate-free framework of [(CH3)2NH2]2[Zn8O3(FDC)6] (Zn8-de). Zn8-de displays gated adsorption for C2H2 and type-I adsorption for CO2, attributed to the framework flexibility and the different interactions between the gas molecules and the host framework.

Effect of body mass index on the association between alcohol consumption and the development of chronic kidney disease.

The influence of body mass or metabolic capacity on the association between alcohol consumption and lower risks of developing chronic kidney disease (CKD) is not fully elucidated. We examined whether the body mass index (BMI) affects the association between drinking alcohol and CKD. We defined CKD as an estimated glomerular filtration rate decline < 60 mL/min/1.73 m2 and/or positive proteinuria (≥ 1+). Participants were 11,175 Japanese individuals aged 40-74 years without baseline CKD who underwent annual health checkups. Daily alcohol consumption at baseline was estimated using a questionnaire, and the participants were categorized as "infrequent (occasionally, rarely or never)," "light (< 20 g/day)," "moderate (20-39 g/day)," and "heavy (≥ 40 g/day)." Over a median 5-year observation period, 936 participants developed CKD. Compared with infrequent drinkers, light drinkers were associated with low CKD risks; adjusted hazard ratios (95% confidence intervals) were 0.81 (0.69-0.95). Stratified by BMI (kg/m2), moderate drinkers in the low (< 18.5), normal (18.5-24.9), and high (≥ 25.0) BMI groups had adjusted hazard ratios (95% confidence intervals) of 3.44 (1.60-7.42), 0.75 (0.58-0.98), and 0.63 (0.39-1.04), respectively. Taken together, the association between alcohol consumption and CKD incidence was not the same in all the individuals, and individual tolerance must be considered.

New enzyme-targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer.

Kochi oxydol radiation therapy for unresectable carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in Japan. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide. The mixture is injected intratumorally just before radiation therapy (RT) several times. KORTUC II has the effect of neutralizing antioxidant enzymes, while increasing the oxygen tension into the tumor tissue, and achieves marked local effects without notable adverse events. The present report describes cases in which KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC). The present study included 30 patients with LABC (n=9) or LRBC (n=21) aimed at local control of tumors, who were followed up for ≥3 months after treatment. The irradiation dose and extent fields were determined by the attending physicians considering various patient factors, such as a performance status, prognosis and presence or absence of adjuvant therapy. The median irradiation dose was 60.4 Gy3.5 (43.6-76.1 Gy3.5) based on the calculation of equivalents of 2 Gy fractions, and the median total number of sensitizer injections was 5 (2-7) times. The median maximum tumor shrinkage was 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response. The proportion with loco-regional control at 1, 2 and 3 years was 100, 94.7 and 75.4%, respectively, and progression free survival after RT at 1 and 2 years was 59.0 and 24.1%, respectively. KORTUC II exhibited high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and promising RT method because it is safe and has an excellent radio-sensitizing effect.

Stabilization of radical active species in a MOF nanospace to exploit unique reaction pathways.

We synthesized a metal-organic framework (MOF) using a ligand bearing haloalkoxy chains as a radical precursor. The radicals generated in the MOF upon photoirradiation were stable even at 250 K or under an O2 atmosphere, despite radicals generated from the ligand decomposing at 200 K; thus, the regular arrangement of radicals effectively stabilized them. Moreover, a unique photoproduct was obtained only in the MOF, indicating that the confinement effect in the nanospace enabled a specific reaction that did not occur in the bulk state. We propose a new platform for exploring chemical reactions and materials based on reactive species.

Advanced esophagogastric junction cancer with brain, bone and gastric intramural metastases responding to combined modality therapy.

A 63-year-old man was admitted to our hospital in March 2017 with dysphagia and right homonymous hemianopsia. We diagnosed him with esophagogastric junction cancer (adenocarcinoma) with metastases to the cerebral occipital lobe, bone, and lymph nodes. After one cycle of 5FU + cisplatin (FP), the brain metastasis was resected because of the hemiplegic symptoms he developed. Histology of the resected tissue showed no viable tumor cells. After three cycles of FP, the primary lesion and metastases were resolved. Upper gastrointestinal endoscopy revealed a scar at the primary site. This was considered a complete response (CR). In April 2018, CT revealed a mass at the cardia, which was considered as lymph node metastases with gastric wall invasion. Although two additional cycles of FP were administered for recurrent tumors, the efficacy was progressive. In August 2018, proximal gastrectomy and D1 + lymph node dissection were performed. The pathological diagnosis was gastric intramural metastases and lymph node metastases (ypN1 [2/22]). Weekly paclitaxel therapy was administered for three months after surgery. Two years have passed since the last surgery without recurrence. We report a rare case of esophagogastric junction cancer with brain, bone, and gastric intramural metastases that responded to combined modality therapy.

Fabrication of a Kagomé-type MOF Membrane by Seeded Growth on Amino-functionalized Porous Al2 O3 Substrate.

In this study, we report an efficient fabrication method for the membrane of a metal-organic framework (MOF) (Kgm-OEt) which is one kind of kagomé-type MOF with a two-dimensional (2D) sheet structure having one-dimensional (1D) channels suitable for separation of H2 from other larger gases. The Kgm-OEt seed layer was created on an Al2 O3 substrate using layer-by-layer (LBL) growth, then a membrane was fabricated by secondary growth. The membrane on a 3-aminopropyltriethoxysilane (APTEs)-treated substrate obtained in this method was continuous and defect-free with the crystal orientation suitable for gas transportation, while the membrane grown on an unmodified substrate was loosely packed with unfavorable crystal orientation.

Triplet Carbene with Highly Enhanced Thermal Stability in the Nanospace of a Metal-Organic Framework.

Triplet carbenes (TCs) are of great interest due to their magnetic properties and reactivity, which descend from TCs' unique electronic state. However, the reactivity and stability of TCs are usually a trade-off, and it is difficult to achieve both at the same time. In this work, we were able to enhance the thermal stability of a TC species while maintaining its reactivity by confining them in the nanospace of a metal-organic framework (MOF). We synthesized a new MOF using a TC precursor; subsequently, TCs were generated by photostimulation. The TCs generated in the MOF nanospace were detectable up to 170 K, whereas their non-MOF-confined counterparts (bare ligand) could not be detected above 100 K. In addition, the reactivity of TC generated in MOF with O2 was drastically improved compared to that of bare ligand. Our approach is generally applicable to the stabilization of highly reactive species, whose reactivity needs to be preserved.

Discovery of Atabecestat (JNJ-54861911): A Thiazine-Based ß-Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor Advanced to the Phase 2b/3 EARLY Clinical Trial.

Accumulation of amyloid ß peptides (Aß) is thought to be one of the causal factors of Alzheimer's disease (AD). The aspartyl protease ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting protease for Aß production, and therefore, BACE1 inhibition is a promising therapeutic approach for the treatment of AD. Starting with a dihydro-1,3-thiazine-based lead, Compound J, we discovered atabecestat 1 (JNJ-54861911) as a centrally efficacious BACE1 inhibitor that was advanced into the EARLY Phase 2b/3 clinical trial for the treatment of preclinical AD patients. Compound 1 demonstrated robust and dose-dependent Aß reduction and showed sufficient safety margins in preclinical models. The potential of reactive metabolite formation was evaluated in a covalent binding study to assess its irreversible binding to human hepatocytes. Unfortunately, the EARLY trial was discontinued due to significant elevation of liver enzymes, and subsequent analysis of the clinical outcomes showed dose-related cognitive worsening.

Trapping and Releasing of Oxygen in Liquid by Metal-Organic Framework with Light and Heat.

Nanoporous materials can adsorb small molecules into their nanospaces. However, the trapping of light gas molecules dissolved in solvents suffers from low concentration and poor adsorption affinity. Here, the reversible trapping and releasing of dissolved oxygen are shown through integrating photosensitization and chemical capturing abilities into a metal-organic framework (MOF), MOMF-1. 9,10-Di(4-pyridyl)anthracene (dpa) ligands in MOMF-1 generates singlet oxygen from triplet oxygen under photoirradiation without additional photosensitizers, and successively reacts with it to produce anthracene endoperoxide, forming MOMF-2, which is proved crystallographically. The reverse reaction also proceeds quantitatively by heating MOMF-2. Moreover, MOMF-1 exhibits excellent water resistance, and completely removes oxygen of ppm order concentrations in water. The new material shown in this report allows controlling of the amount of dissolved oxygen, which can be applicable in various fields relating to numerous oxidation phenomena.

Molecular motion in the nanospace of MOFs upon gas adsorption investigated by in situ Raman spectroscopy.

Molecular motions taking place in the nanospace of metal-organic frameworks (MOFs) are an interesting research subject, although not yet fully investigated. In this work, we utilized in situ Raman spectroscopy in the ultralow-frequency region to investigate the libration motion (including the rotational motion of phenylene rings) of MOFs, in particular [Cu2(bdc)2(dabco)] (Cu-JAST-1), where bdc = 1,4-benzenedicarboxylate and dabco = 1,4-diazabicyclo[2.2.2]octane. The libration mode of Cu-JAST-1 was found to be significantly suppressed by the adsorption of various guest molecules, such as CO2, Ar, and N2. In addition, an appreciable correlation between the libration mode and adsorption equilibrium time was identified, which provides useful novel tools in the design of MOFs acting as molecular adsorption and separation materials.

Longitudinal analysis of premotor anthropometric and serological markers of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder in which nonmotor symptoms, such as constipation and hyposmia, precede the onset of motor symptoms by 20 years. The aim of this study was to identify biomarkers at the premotor stage of PD. We assessed the differences in longitudinal changes in anthropometric and serological indices obtained from health check-up data before and after the onset of motor symptoms between male and female PD patients and healthy subjects. We enrolled 22 male and 23 female PD patients and 60 male and 60 female healthy controls. A mixed-effects model was used to estimate the trajectory of each clinical marker over the years before and after motor symptoms onset in the PD subjects, which were then compared with the trajectories of the healthy controls. The results showed a premotor blood pressure increase in female PD patients and premotor decreases in haematocrit, total cholesterol and low-density lipoprotein cholesterol in the male patients. Our results indicated that blood pressure, haematocrit and serum cholesterol levels are potential premotor markers of PD. Additionally, the changes in anthropometric and serological indices before PD motor symptoms onset were sex specific.

Subjects at risk of Parkinson's disease in health checkup examinees: cross-sectional analysis of baseline data of the NaT-PROBE study.

INTRODUCTION: The present study aimed to survey the prevalence of prodromal symptoms of Parkinson's disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. METHODS: We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. RESULTS: Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p < 0.001) and ESS (9.6 ± 5.0 vs. 6.3 ± 3.2, p < 0.001), in addition to SCOPA-AUT, SAOQ, and RBDSQ. Male at-risk subjects showed lower values of hemoglobin (14.8 ± 1.3 vs. 15.0 ± 1.1, p = 0.032) and low density lipoprotein cholesterol (114.5 ± 30.3 vs. 123.0 ± 28.9, p = 0.004) than the examinees reporting no prodromal symptoms. CONCLUSION: Approximately 6% of the population aged 50 years or older was at risk for PD. Male at-risk subjects had mild hematological and metabolic changes relevant to PD.

Direct observation of dimethyl sulfide trapped by MOF proving efficient removal of sulfur impurities.

Here, we report the adsorptive removal of trace amounts of dimethyl sulfide (DMS) using metal-organic frameworks (MOFs). Cu2+-based MOFs with open metal sites (OMSs), [Cu3(btc)2] (HKUST-1), where btc = 1,3,5-benzenetricarboxylate, and without OMSs, [Cu2(bdc)2(dabco)] (Cu-JAST-1), where bdc = 1,4-benzenedicarboxylate and dabco = 1,4-diazabicyclo[2.2.2]octane, were investigated for the removal of DMS to compare their performance with that of Ag-Y zeolite, which is currently widely used in industry. HKUST-1 exhibited a considerably higher adsorption capacity for DMS than the other adsorbents, which was confirmed by breakthrough measurements. The adsorption state of DMS with HKUST-1 was directly revealed by single-crystal X-ray diffraction (SXRD) analysis and in situ Raman spectroscopy. In addition, it was shown that DMS can be removed by HKUST-1 even under humid conditions.

High-dose-rate interstitial brachytherapy with hypoxic radiosensitizer KORTUC II for unresectable pelvic sidewall recurrence of uterine cervical cancer: a case report.

In order to improve oncologic outcomes in radiotherapy treatments of patients with unresectable pelvic sidewall recurrences of uterine cervical cancer, we combined high-dose-rate interstitial brachytherapy (HDR-ISBT) with newly tested hypoxic radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC II), an enzyme-targeting radiosensitization treatment involving intra-tumoral injection of sodium hyaluronate mixed with hydrogen peroxide. We report on a 63-year-old patient referred to our department with an extensive pelvic sidewall recurrence of uterine cervical cancer after initial hysterectomy. The tumor size was 55 × 25 × 80 mm, with a calculated volume of 89.7 cc. Whole pelvic irradiation of 50 Gy in 25 fractions was administered, combined with weekly cisplatin injections. KORTUC II injections were given two times: at day 21 (42 Gy) and at day 24 (48 Gy). After finishing whole pelvic irradiation, HDR-ISBT of 25 Gy in 5 fractions b.i.d. over 3 days was administered. KORTUC II was also injected at the time of implantation. Dose-volume histogram (DVH) values for clinical target volume were D90, D98, and D100 of 6.0, 5.0, and 3.5 Gy per fraction, respectively. D2cc values were 2.1, 4.1, 3.2, and 2.0 Gy per fraction for the bladder, rectum, sigmoid colon, and small bowel, respectively. No acute adverse events ≥ grade 3 were observed. Repeated grade 3 pyelonephritis occurred as a late complication at 11, 24, and 26 months after the treatment, and was successfully resolved with antibiotics. Moreover, grade 2 late toxicity was documented, including sciatic neuralgia, lower limb lymphedema, and urinary incontinence. At present, 32 months after HDR-ISBT, the patient remains free of disease, with no toxicity-related deterioration in physical condition.