Search

Objective The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD). Methods In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments. Results Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined. Conclusions The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases.

Background Disaster-related stress can increase blood pressure and the incidence of cardiovascular diseases. However, the role of massive disasters in the development of end-stage kidney disease (ESKD) remains unknown. We investigated the incidence and different causes of dialysis initiation in patients with chronic kidney disease in a city affected by the Great East Japan Earthquake. Methods This was a single-center, retrospective observational study. All patients who initiated or were treated with dialysis at Kesennuma City Hospital between 2007 and 2020 were enrolled. The year of dialysis initiation was retrospectively determined based on the initiation date. The causative renal diseases that led to the need for dialysis initiation were divided into four groups: diabetic nephropathy, hypertensive renal disease, glomerulonephritis, and others. Results Age at dialysis initiation differed significantly among the four groups (p = 0.0262). There was a significant difference in the numbers of the four groups before and after the Great East Japan Earthquake (p = 0.0193). The age of hypertensive renal disease patients was significantly higher than those of patients with diabetic nephropathy (p = 0.0070) and glomerulonephritis (p = 0.0386) after the disaster. The increasing number of dialysis initiations after the Great East Japan Earthquake appeared to be associated with changes in hypertensive renal diseases; the number peaked after 10 years. Conclusions There was an increase in the number of dialysis initiations, especially caused by hypertensive renal diseases, for up to 10 years after the Great East Japan Earthquake. Graphic abstract

Organized chronic subdural hematoma is a neurological condition characterized by organized clot formation inside the hematoma. Unlike nonorganized chronic subdural hematoma with persistent bleeding inside, organized subdural hematoma is often a nonurgent condition that does not require emergency drainage, unless progressive cerebral compression with neurological disturbances is present. However, as the CT values in organized clot formation and active bleeding fall in similar ranges, distinguishing these 2 conditions with different emergency levels based on brain CT alone is sometimes difficult. Here, we describe the case of a 78-year-old man with persistent nocturia who was referred to our hospital. He had a history of head trauma on the left side about 1 year ago, followed by neurosurgery at another hospital. Brain CT revealed a multiseptated subdural space and a mixed-density hematoma without gradation density on the contralateral side of the past head trauma region. Based on the lack of progressive neurological disturbances and the absence of gradation density in CT values inside the hematomas, his condition was judged as nonurgent, and emergency drainage was spared. One year after his first visit to our hospital, the patient experienced a normal life without any neurological disturbances, except for nocturia. The absence of gradation density in CT values along the gravity direction inside the organized hematoma may be a clue to estimate nonurgency without persistent active bleeding inside.

The increasing prevalence of advanced paternal age (APA) has mirrored the rise in maternal age. APA is associated with an increased risk of de novo pathogenic single-nucleotide variants, but this topic has been much less frequently discussed than advanced maternal age (AMA). To explore the awareness of pregnant women regarding paternal age effect (PAE) disorders, a self-administered questionnaire survey was conducted for pregnant women at their first prenatal visit before 17 weeks of gestation. A total of 120 valid respondents (95.2%) were included in the analyses. Of these, 63.3% of pregnant women were aware of PAE disorders. This was markedly lower than the 90.8% recognition of maternal age effect (MAE) disorders. One-third of women with awareness of MAE disorders were not aware of PAE disorders. Pregnant women who were parous, older than their male partners, with knowledge of prenatal testing prior to this pregnancy, and with experience of prenatal testing in a prior pregnancy were significantly more aware of PAE disorders than others. Awareness of PAE disorders was not associated with undergoing prenatal testing during the present pregnancy. Our results show that the prevalence of pregnant women’s awareness of PAE disorders was lower than that of MAE disorders. The current study served as a preliminary baseline of information about pregnant women’s awareness of PAE disorders. With the introduction of non-invasive prenatal testing, which has the potential to identify PAE disorders, these findings will help the development of a framework for comprehensive prenatal genetic counseling for APA pregnancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12687-021-00555-y.

Objective Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains the world's largest public health concern in 2021. A history of close contact with infectious patients is a factor that predicts a positive SARS-CoV-2 test result. Meanwhile, the precise predictive value of symptoms suggestive of COVID-19 has not been fully elucidated. This study aimed to clarify the predictive and discriminatory value of each clinical symptom suggestive of COVID-19. Methods This study enrolled participants who were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction using a nasopharyngeal swab between November 2020 and January 2021. All enrolled patients were evaluated for data regarding the presence and closeness of contact with infectious patients and comprehensive clinical features (i.e., fever, cough, dyspnea, fatigue, dysosmia, and dysgeusia). Results Among the 1,744 tested participants, 144 tested positive for SARS-CoV-2. In the test-positive group, self-reported cough, fatigue, dysosmia, and dysgeusia were significant predictors of COVID-19, independent from a history of close contact. In particular, the presence of dysosmia was the strongest predictor of COVID-19 in both univariate and multivariate analyses. Among the 42 patients with self-reported dysosmia, 25 (59.5%) were SARS-CoV-2 test-positive. Self-reported dysosmia was reported by 25 (17.4%) of the 144 patients who tested positive for SARS-CoV-2, and 15 (60.0%) of the 25 COVID-19 patients with dysosmia had accompanying dysgeusia. Conclusion The presence of dysosmia was reported by 10-25% of patients with COVID-19, and is a significant predictor of COVID-19 infection, independent from a history of close contact.

Objective Radioactive iodine (RAI) therapy is effective for differentiated thyroid cancer (DTC) patients with lung metastasis. However, some patients have a poor prognosis despite the RAI accumulation. The utility of inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), has been reported as a prognostic factor for many carcinomas. This study aimed to investigate the risk factors related to DTC patient survival with RAI-avid lung metastasis and to attempt risk stratification. Design and methods This retrospective study included 123 patients with RAI-accumulating lung metastatic DTC. The cause-specific survival (CSS) rate from the time of detection of lung metastasis was tested using the Kaplan–Meier log-rank test, and the multivariate analysis was calculated using the Cox proportional hazards model. NLR was retrospectively calculated using the blood sample collected before initial RAI treatment. The NLR cutoff value was 2.6 on the ROC curve. Results Age ≥ 55 years at the time of operative treatment, follicular carcinoma, lung metastasis tumor ≥ 10 mm in diameter, age ≥ 55 years at the time of detection of lung metastasis, age ≥ 55 years at the time of RAI treatment, and NLR ≥ 2.6 at the initial RAI treatment were predictive of decreased CSS. Multivariate analysis identified that the independent prognostic factors were lung metastatic tumor ≥ 10 mm in diameter and NLR ≥ 2.6. Patients in the high-risk group with both factors had significantly lower CSS rates than those in the low- and intermediate-risk groups with one or none of these factors. Conclusions The high-risk group patients had significantly poorer survival, and these patients could be considered as future candidates for tyrosine kinase inhibitor therapy.

Background Esophageal achalasia causes dysphagia following impaired relaxation of the lower esophageal sphincter due to the degeneration of Auerbach’s plexus in the esophageal smooth muscle. Recently, peroral endoscopic myotomy (POEM) has become one of the preferred treatment options for esophageal achalasia. However, pathomorphological changes after POEM have not been well examined. Case presentation A 65-year-old man with a history of POEM for esophageal achalasia was diagnosed with clinical stage II (cT2-N0-M0) thoracic esophageal squamous cell carcinoma and was consequently treated with neoadjuvant chemotherapy followed by thoracoscopic esophagectomy. Intraoperatively, the esophagus appeared dilated, reflecting esophageal achalasia; however, fairly slight fibrous adhesions were observed between the esophagus and the pericardial surface despite previously performed POEM via an anterior incision. Histopathological examination revealed esophageal wall thickening, edema, and fibrosis extending from the lamina propria to the submucosa. Besides, the majority of the inner layer and some proportion of the outer layer of the muscularis propria were found to be missing or atrophic at the esophagogastric junction (EGJ). No ganglion cells could be detected at the Auerbach’s plexus. Conclusions The previous history of POEM did not affect circumferential mediastinal periesophageal dissection during thoracoscopic esophagectomy. Nevertheless, a large proportion of the inner layer of the muscularis propria at the EGJ level seemed to have become lost or atrophic because of the POEM procedure.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world’s largest public health concern. This study evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.

Vancomycin-resistant enterococci (VRE) are prominent causes of nosocomial infections. Japanese traditional (Kampo) medicine promotes intestinal immunity and protects against bacterial infections. We assessed potential differences in the clinical course of VRE-positive patients, based on their characteristics and treatment with Kampo medicines. This retrospective observational study collected data from VRE-positive patients from August 2018 to July 2019 at a tertiary-care hospital in Japan. The data of 122 consecutive VRE-positive inpatients were analyzed. Sixty-nine patients were treated with probiotics, among whom, 18 were further treated with Kampo medicines. Twenty-six of the 122 patients subsequently died. In univariate analyses, subsequent VRE negative conversion significantly reduced the mortality of VRE-detected patients (p = .0003). Administration of probiotics (p = .0065) and Kampo medicines with probiotics (p = .0002), especially of the Kampo medicine hochuekkito (p = .0014), and a higher serum albumin level positively contributed to the subsequent VRE negative conversion. Multivariate analyses demonstrated that Kampo medicines and body mass index contributed to VRE negative conversion. Hochuekkito shortened the time needed for VRE negative conversion (p = 0.0485). Administration of Kampo medicines, especially of hochuekkito, in addition to probiotics in VRE patients may promote VRE negative conversion.

Most anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after ≥ 10 years of follow-up served as the control group. There were no clinicopathological differences between the two groups at initial surgery including age, gender, tumor size, lymph node metastasis, distant metastasis, extrathyroidal extension, histologic subtype, and treatment. The median time from the initial thyroid surgery to anaplastic transformation in the nodal recurrence was 106 months (range 6 to 437 months). Mutational analyses showed recurrent PTCs with anaplastic transformation had a high prevalence of BRAFV600E mutation (8/9) and TERT promoter mutation (9/9), both of which were detected in primary tumors. PIK3CAH1047R mutation was detected in one case. No case had RAS mutation. Nineteen recurrent PTCs without anaplastic transformation harbored BRAFV600E mutation and seventeen of these had TERT promoter mutation. Unlike primary tumors with subsequent nodal anaplastic transformation, TERT promoter mutation was only present in the metastatic nodal recurrence from 4 patients without transformation. No patients had neither high-grade features (necrosis and increased mitotic activity) nor solid/insular growth or hobnail cell features in their primary tumors. In the group of patients with transformation, 3 had solid/insular growth in the lymph node metastasis at the time of primary tumor resection (one displaying nuclear features of PTC and solid growth with increased mitotic activity, one with insular component consistent with poorly differentiated carcinoma component, and one displaying nuclear features of PTC and solid growth), and additional 2 patients had solid/insular growth with no high-grade features or poorly differentiated carcinoma component at the time of subsequent nodal recurrence prior to anaplastic transformation. Hobnail cell features were exclusively seen in subsequent metastatic lymph nodes prior to anaplastic transformation. The control group lacked solid/insular growth and hobnail cell features in the metastatic nodal disease. Aberrant p53 expression and loss of TTF-1 featured tumor components with anaplastic transformation. This series identified a subset of recurrent PTCs with TERT promoter mutation was prone to undergo anaplastic transformation, and that solid/insular growth and hobnail cell features were morphological predictors of anaplastic transformation in the nodal recurrence.

Purpose There are no reports showing the significance and effective range of dissection for patients with lateral lymph node metastasis (LLNM). This study aimed to investigate the indications for lateral lymph node dissection (LLND) in patients with LLNM based on prognostic factors and recurrence types. Methods We reviewed 379 patients with advanced rectal cancer who were treated with total mesorectal excision plus LLND. We analyzed background factors and survival times of patients who had LLNM to determine prognostic factors and recurrence types. Results Pathological LLNM occurred in 44 (11.6%). Among patients with LLNM, the predictors of poor prognoses, according to univariate analysis, were > 3 node metastases, the presence of node metastasis on both sides, and spreading beyond the internal iliac lymph nodes. Moreover, LLNM beyond the internal iliac region was found to be an independent prognostic risk factor. Twenty-eight of the 44 patients with lateral lymph node metastasis (64%) relapsed, 22 of whom had distant metastases and 11 of whom experienced local recurrences. Among the latter group, nine (20%) and two (5%) had recurrences in the central and lateral pelvis, respectively. Conclusion The therapeutic benefit of resection was high, especially in patients with ≤ 3 positive lateral lymph nodes, one-sided bilateral lymph node areas, and positive nodes localized near the internal iliac artery.

Introduction: The characteristics of somatic symptoms seen at the first hospital visit in patients with psychogenic backgrounds remain poorly elucidated till date. Methodology: A total of 277 patients who visited the Department of General Medicine at a single university hospital with somatic symptoms were prospectively enrolled in this study. The eventual definite diagnoses were classified into the following three groups: non-psychogenic disease (n = 128), psychogenic symptoms (n = 131), and mental illness (n = 18). Subsequently, the chief complaints and other background information of the patient obtained at the first visit were compared among the three groups. Results: More than half of the patient with non-psychogenic diseases (60.2%) presented with a single complaint at their first hospital visit; contrarily, less than half of the patients with psychogenic symptoms (23.7%) or mental illnesses (22.2%) presented with a single complaint at the first visit. Approximately

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the world's largest public health concern in 2021. This study evaluated the associations of the prevalence of airway symptoms among the tested individuals and data regarding the natural environmental factors with the weekly number of newly diagnosed COVID-19 patients in Sendai City (N

Background: The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results: In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories: No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions: LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF.

The progressive patterns of neurological disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and the significance of clinical relapses to the progressions of neurological disability in these diseases have not been fully elucidated. In this study, to elucidate the impact of relapses to the progression of accumulated neurological disability and to identify the factors to affect the progression of neurological disability in MS and NMOSD, we followed 62 consecutive MS patients and 33 consecutive NMOSD patients for more than 5 years with the clinical symptoms, relapse occurrence, and Expanded Disability Status Scale (EDSS) in the chronic phase. All enrolled MS patients were confirmed to be negative for serum anti-myelin oligodendrocyte glycoprotein antibody. As a result, patients with NMOSD showed significantly severer neurological disability at 5 years from onset than MS patients. Progression in EDSS score was almost exclusively seen after clinical attacks in NMOSD, whereas progression could be observed apart from relapses in MS. Neurological disability did not change without attacks in NMOSD, whereas it sometimes spontaneously improved or deteriorated apart from relapses in MS (p

A 66‐year‐old man with a 2‐year history of suspected scalp eczema with excessive dandruff developed painful swollen joints in the extremities. Four months after developing polyarthritis and polydactylitis, eczema gradually spread to the face. He was referred to our hospital for intractable scalp and facial eczema and polyarthritis. Based on the appearance of the head and facial skin lesions, psoriasis was suspected. Treatment with apremilast (a phosphodiesterase‐4‐inhibitor) was initiated, which swiftly alleviated the skin lesions. The joint deformities persisted, but the pain in the joints disappeared. This case implies that psoriatic arthritis should be suspected even if psoriatic skin lesions are localized to the scalp., Psoriatic arthritis was observed in a middle‐aged man with the skin lesions localized to scalp area. Because a delayed diagnosis may result in irreversible joint deformity, close collaboration with dermatologists is essential for early diagnosis of psoriatic arthritis in patients with localized skin lesions remote from the site of arthritis or dactylitis.

Background A recent investigation reported that 92.7% Japanese family physicians have prescribed Kampo medicine (KM). KM can treat a wide variety of conditions from mental disorders to physical weaknesses. However, the characteristics and course of patients treated with KM at the Department of General Medicine remain unclear. Aims To investigate the characteristics and course of patients treated with KM in our hospital. Methods Data on medical history, complaints, course after Kampo treatment, and Hamilton Depression Rating Scale (HAM‐D) scores were retrogradely collected. The background of patients who received Kampo treatment was compared to that of patients who did not. Result Of 362 patients, 51 were treated with KM. Symptoms for which KM was prescribed included pain, general malaise, or sensory disturbance of extremities. All patients treated with KM were screened and initially diagnosed with a functional disorder or noncritical condition. KM including a crude drug of saiko such as hochuekkito, shigyakusan, shosaikoto, and yokukansan, was frequently prescribed for patients. Subjective symptoms showed improvement (53%) and no change (47%), while worsening was not observed in any patient. HAM‐D scores showed that patients treated with KM had higher anxiety levels and related symptoms as well as a higher frequency of mental disorders prior to presenting at the hospital. Conclusion Most complaints of the patients treated with KM were pain, general malaise, and sensory disturbance. KM is more likely to be prescribed in patients with health‐related anxiety or a history of mental disorders., Kampo medicine is more likely to be prescribed in patients with health‐related anxiety or a history of mental disorders who visit the Department of General Medicine.

PURPOSE To report the effect of frontalis linkage without intraoperative eyelid elevation for the management of myopathic ptosis. METHODS Retrospective analysis of 21 (42 eyelids) myopathic patients with bilateral ptosis who were operated between 1999 and 2017. All patients had orbicularis weakness and poor or absent Bell's phenomenon. Surgery consisted of using an autogenous fascia sling to link the tarsal plate to the frontalis muscle without any degree of intraoperative eyelid elevation. The main outcome measures were margin reflex distance, brow height and degree of brow excursion and degree of lagophthalmos, and exposure keratitis. RESULTS After surgery, there were significant changes (p

Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein–creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.

In 2006, we established a scar/keloid-specialized unit in the Department of Plastic, Reconstructive, and Aesthetic Surgery at Nippon Medical School (NMS) in Tokyo, Japan. In the ensuing 15 years, we treated approximately 2,000 new scar/keloid patients annually. This extensive experience has greatly improved the efficacy of the treatments we offer. Therefore, we discuss here the latest NMS protocol for preventing and treating keloids and hypertrophic scars. While this protocol was optimized for Japanese patients, our experience with a growing body of non-Japanese patients suggests that it is also effective in other ethnicities. The extensive evidence-based experience underlying the NMS protocol suggests that it may be suitable as the foundation of a standard international prevention/treatment algorithm for pathological scars.

A 97-year-old female presented with spontaneous acute-onset palpebral hyperemia and edema of the right eye that had progressively worsen over the previous three days. These signs did not suggest possible carotid-cavernous fistula until a second examination 72 h later, during which the patient exhibited significant progression. Despite embolization, the patient exhibited sustained corneal edema, clots, and turbidity in the aqueous humor, which resulted in permanent visual loss. A greater level of clinical suspicion for possible carotid-cavernous fistula is warranted on initial presentation of palpebral hyperemia and edema to prevent possible irreversible vision loss.

Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p p p = 0.0027), and neutrophil (p

We have investigated a prototype triggerless data acquisition (DAQ) system for charmed-baryon spectroscopy at J-PARC. A special time-to-digital converter (TDC) dedicated to continuous timing measurement without any external trigger was developed. A high dynamic range of the order of 1010 for the timing measurement was realized by introducing the heartbeat method, which periodically generates a delimiter datum. DAQ software receiving and filtering the data stream from the TDCs was also developed based on a message-queue application programming interface (API), FairMQ. We tested the prototype DAQ system with detectors using electrons and positrons converted from a bremsstrahlung photon beam with a rate condition of up to 1.9 MHz/1-mm detector segment. The DAQ received a 5.4 Gbps data stream from six TDCs and merged them to a complete data set. After sorting a certain portion of the data, the software searched for a set of corresponding data fragments in response to the penetration of a positron or electron using time separation between detector hits in the time axis and removed unnecessary hits. Around 25 GB RAM and 25 CPU threads were required for the online computing power under the test conditions. No silent data drop in the DAQ software was observed.

A 51-year-old afebrile man visited the hospital with acute severe neck pain with stiff neck, but cervical CT showed no calcification around the odontoid process. Cervical MRI revealed prevertebral hyperintense area of edema at the C1-C5 vertebral bodies, providing the diagnosis of retropharyngeal calcific tendinitis. The patient was spared for lumbar puncture, and his symptoms swiftly disappeared only with oral NSAIDs.

Japanese herbal medicines (HMs) cause adverse drug reactions (ADRs); however, solid nodule formation is uncommon. In this report, we aimed to show that ADRs with HM can mimic lung cancer. A 63-year-old man complained of back pain. His physician prescribed a traditional Japanese HM, Keishikajutsubuto, which alleviated his symptoms. After 4 weeks, a chest radiograph showed multiple lung nodules that were absent 6 months earlier; the patient did not have cough, fever, or dyspnea. Computed tomography (CT) showed multiple, bilateral lung nodules; however, blood tests and lung biopsy showed no abnormalities, ruling out interstitial pneumonia and lung cancer. Three months after the HM was discontinued, CT showed resolution of the lesions. Interstitial pneumonia was reported as a side effect of HM; however, no such side effect was reported for Keishikajutsubuto. When a patient presents with multiple lung nodules, a side effect of HM should be considered as a differential diagnosis.

Highlights • Uterine laceration is extremely rare and little known, however it sometimes causes massive intraperitoneal bleeding and has poor prognosis. • Inner myometrial laceration may be caused by intrapartum physical stress, whereas uterine laceration in relatively early pregnancy might be occurred by tissue inadaptable for uterine enlargement. • To diagnosis uterine laceration in early pregnancy is quite difficult because of the absence of specific clinical findings. • Not only uterine rupture but also uterine laceration should be considered, and exploratory laparotomy should be performed appropriately when hemoperitoneum is strongly suspected., Introduction Although uterine rupture is well discussed, uterine laceration and partial myometrial laceration are little known. A previous report hypothesized that the stress of labor was associated with uterine laceration. Presentation of case We present a rare case of uterine laceration in a patient in the second trimester. A 34-year-old primigravida woman at 16 weeks’ gestation without a history of uterine surgery complained of sudden low abdominal pain. Ultrasonography showed fetal death and intraperitoneal free fluid. A laparotomy was performed, and partial uterine laceration in the posterior wall along with active bleeding was confirmed. Discussion The etiology of uterine laceration in early pregnancy might be different from both classical uterine rupture and previously published uterine laceration. We hypothesized that tissue inadaptable for uterine enlargement, such as that owing to endometriosis and subtle injury by surgical approach, may be associated with the onset mechanism. Conclusion The diagnosis of uterine laceration in early pregnancy is quite difficult because of the absence of specific clinical findings. However, it sometimes causes massive intraperitoneal bleeding and has poor prognosis. Therefore, when uterine laceration is suspected as a cause of hemoperitoneum in a pregnant women, clinicians should perfume exploratory laparotomy appropriately.

Background: The ultimate clinical goal of advanced cancer treatment is improvement of survival. Tyrosine kinase inhibitors (TKIs) were recently approved for radioiodine-refractory differentiated thyroid carcinoma (RR-DTC) that is resistant to conventional therapies since they have significant potential to improve survival in patients who previously had no more treatment strategies available. However, eligible patients are limited in clinical practice, making it difficult to accurately determine the efficacy of TKIs. Patients and Methods: We retrospectively analyzed the efficacy of lenvatinib at a single institution, enrolling 42 RR-DTC patients. Results: The best overall response was partial remission in 26 (62%) patients, stable disease in 10 (24%) patients, and progressive disease (PD) in 6 (14%) patients. The results indicated three-year overall survival (OS) and progression-free survival rates of 51.0% and 32.4%, respectively. Twenty-three (55%) patients had backgrounds that did not match the inclusion criteria of the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. Furthermore, PD-experienced patients individually decided whether to continue lenvatinib, and 17 (41%) made the decision themselves; these patients had a three-year OS of 43.0% and postprogression survival (PPS) of 13.3 [95% confidence interval 6.1-not reached] months. Conclusions: Our real-world investigation revealed that patients have wide-ranging background characteristics, and the decision regarding continuation of therapy after PD is based on the patient's general condition. Our management protocol resulted in good PPS. Furthermore, our results indicated equivalent efficacy of lenvatinib as in the SELECT trial. In conclusion, lenvatinib proved effective for RR-DTC patients in a real-world setting.

Background Severe keloids are currently treated with surgical resection followed by radiation. Radiotherapy is essential for preventing recurrences. Fascia tensile reduction suturing may also prevent recurrence. We asked whether superficial fascia tensile reduction with or without deep fascia tensile reduction reduced skin mechanical tension and yielded good outcomes. Methods Geometric modeling on 3-dimensional anatomic shapes assessed the effect of superficial fascia tensile reduction with or without deep fascia tensile reduction on skin tension. A retrospective cohort study was performed on patients with severe anterior-chest keloids with Japan Scar Workshop-scar scale classification score ≥ 16 who underwent resection plus fascia tensile reduction plus radiotherapy between 2011 and 2016 and were followed for >18 months. Patient characteristics and 18-month postoperative outcomes were examined. Postoperative outcome was defined as rates of keloid disappearance, improvement, and obvious recurrence. Results Maximal mechanical forces placed on the dermis by dermal sutures, dermal sutures plus superficial fascia tensile reduction, and dermal sutures plus superficial fascia tensile reduction plus deep fascia tensile reduction were 4,700, 573, and 697 Pa, respectively. Adding deep fascia tensile reduction to superficial fascia tensile reduction decreased the force on the superficial fascia. Of 77 cohort patients, 27 and 50 underwent superficial fascia tensile reduction and superficial fascia tensile reduction plus deep fascia tensile reduction, respectively. Superficial fascia tensile reduction plus deep fascia tensile reduction patients underwent complete excision more often (60.0% vs 37.0%, P = .046). The groups did not differ in 18-month surgical outcome, including recurrence rate (P = .670). Conclusion Our 2003 study showed that in anterior-chest keloids, resection plus non-fascial suturing plus radiotherapy led to a 43.1% recurrence. Thus, fascia tensile reduction suturing helps reduce anterior-chest keloid recurrence to ∼5.2%. Superficial fascia tensile reduction plus deep fascia tensile reduction is suitable for relatively large keloids that require total resection. Deep fascia tensile reduction may facilitate superficial fascia tensile reduction but may only be useful when it is technically difficult to achieve reduction with superficial fascia tensile reduction alone.

We herein report the case of a 14-year-old girl who had been experiencing chronic fatigue, febricula, and social withdrawal for 20 months. No notable abnormalities were identified during routine checkups at a general pediatric hospital; symptomatic treatments did not affect her condition. She was diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Based on the concepts of Japanese traditional medicine, she was administered shosaikoto-based treatment. After several weeks of treatment, all of the symptoms had been dramatically alleviated, consequently resolving the issue of non-attendance at school. Shosaikoto-based medication may be a therapeutic option for treating ME/CFS in patients presenting with chronic febricula.

A 30‐year‐old man with severe hypoalbuminemia (serum albumin: 0.9 g/dL) was admitted with severe bilateral leg edema and unilateral pleural effusion. Serum anti‐SS‐A and SS‐B antibody levels were abnormally elevated, and his symptoms fulfilled the diagnostic criteria for Sjögren's syndrome. Technetium‐99m albumin scintigraphy revealed protein leakage from a large area of the small intestine. Immunohistochemistry revealed perivascular deposition of C1q, C3d, and immunoglobulin G in the duodenal mucosa. The patient was diagnosed with protein‐losing gastroenteropathy associated with Sjögren's syndrome. Within 2 months of treatment with oral prednisolone and mycophenolate mofetil, the clinical symptoms of hypoalbuminemia and Sjögren's syndrome disappeared completely., A middle‐age man with severe hypoalbuminemia and severe edema. The patient was diagnosed with Sjögren's syndrome associated with protein‐losing enteropathy by protein scintigraphy and pathological examination of colon. After treatment of immunosuppressant, the clinical symptoms disappeared completely.

PURPOSE To describe the late results of the placement of skin graft over conjunctiva-Muller muscle complex in 3 patients with ablepharon-macrostomia syndrome (AMS) and to review the procedures used to manage the upper eyelids in AMS. METHODS The authors searched the Pubmed database for all articles that used the term "ablepharon-macrostomia syndrome" in any field. Data collection included description of eyelid changes, age at surgery, status of the cornea before surgery, type of eyelid repair, and final outcome. Two previously reported siblings were reevaluated 10 and 15 years after a single reconstructive operation. A new case from Peru is also described. RESULTS Only 15 patients with AMS have been described in 12 articles. In 60% of the cases, the lids were described as absent. The surgical modalities employed to reconstruct the upper eyelids were quite variable, including local flaps, lid sharing procedures, and even a masquerade flap. At long-term follow-up, all 3 cases who underwent upper eyelid lengthening with full thickness skin grafts placed over Muller muscle had clear corneas with a small amount of lagophthalmos. CONCLUSIONS The lids in AMS are not absent and should not be managed with complex reconstructive techniques. Full thickness skin grafts placed over the inner aspect of the palpebral conjunctiva allow permanent eye protection.The upper eyelids in ablepharon-macrostomia syndrome can be permanently lengthened with full thickness skin grafts over Muller muscle.

Purpose: The epithelial-to-mesenchymal transition, the major process by which some cancer cells convert from an epithelial phenotype to a mesenchymal one, has been suggested to drive chemo-resistance and/or metastasis in patients with cancer. However, only a few studies have demonstrated the presence of CD45/CD326 doubly-positive cells (CD45/CD326 DPC) in cancer. We deployed a combination of cell surface markers to elucidate the phenotypic heterogeneity in non–small cell lung cancer (NSCLC) cells and identified a new subpopulation that is doubly-positive for epithelial and non–epithelial cell-surface markers in both NSCLC cells and patients' malignant pleural effusions. Experimental Design: We procured a total of 39 patients' samples, solid fresh lung cancer tissues from 21 patients and malignant pleural effusion samples from 18 others, and used FACS and fluorescence microscopy to check their surface markers. We also examined the EGFR mutations in patients with known acquired EGFR mutations. Results: Our data revealed that 0.4% to 17.9% of the solid tumor tissue cells and a higher percentage of malignant pleural effusion cells harbored CD45/CD326 DPC expressing both epithelial and nonepithelial surface markers. We selected 3 EGFR mutation patients and genetically confirmed that the newly identified cell population really originated from cancer cells. We also found that higher proportions of CD45/CD326 DPC are significantly associated with poor prognosis. Conclusions: In conclusion, varying percentages of CD45/CD326 DPC exist in both solid cancer tissue and malignant pleural effusion in patients with NSCLC. This CD45/CD326 doubly-positive subpopulation can be an important key to clinical management of patients with NSCLC.

Increased intrarenal vascular resistance is suggested to accompany chronic kidney diseases (CKD), which is known to be closely associated with hypertension. However, there are few studies that have examined the relationship between blood pressure and intrarenal vascular resistance. Renal color Doppler ultrasonography is one method that can non-invasively evaluate intrarenal vascular resistance. In this study, we comprehensively studied the correlations between ultrasonic parameters and blood pressure indices to elucidate their relationships. In total, 162 patients with suspected CKD were enrolled for this study. Demographics, blood pressure, blood test, urine test, and renal color Doppler ultrasonography data were obtained. The ratio of diastolic to systolic blood pressure (D/S ratio) and pulse pressure were calculated. Our results indicated strong negative correlations between the renal resistive index (RI) values in all four of the studied kidney regions and the D/S ratio. The RI values also showed significant correlations with diastolic pressure and pulse pressure, but they were weaker. Partial correlation coefficients between pulse pressure, mean arterial pressure, D/S ratio, and RI showed that D/S ratio significantly correlated with RI, but pulse pressure or mean arterial pressure did not. Systolic blood pressure did not correlate with any of the studied ultrasonic values. The negative correlation between RI values and the D/S ratio was still observed in subjects without renal dysfunction or any medications. In conclusion, D/S ratio, rather than pulse pressure or mean arterial pressure, would be the most appropriate index to estimate/calculate/judge intrarenal vascular resistance.

Objective The definite diagnosis of esophageal achalasia is established using manometry, which is performed in patients with suspected achalasia based on the findings of screening examinations, such as upper gastrointestinal endoscopy, chest computed tomography (CT), or a barium swallow test. However, the exact values of test characteristics in these supportive diagnostic examinations remain unclear. Methods We estimated the sensitivity and specificity of characteristic findings in the supportive diagnostic examinations for achalasia by comparing the data of a large number of achalasia patients and others with digestive symptoms. Patients Achalasia patients (n=119) and non-achalasia patients with suspected achalasia and repeated feelings of chest discomfort (n=37) who were treated in a single university hospital. Results Characteristic findings on chest CT (i.e., dilated esophagus, air-fluid level formation) and barium swallow tests were observed in more than 80% of achalasia patients but in less than 10% of non-achalasia patients. In contrast, conventional characteristic findings of upper gastrointestinal endoscopy (i.e., intra-esophageal food debris, feeling of resistance at the esophagogastric junction) were seen in only 40-70% of achalasia patients. In particular, the feeling of resistance at the esophagogastric junction was observed by the examiner in only 30-50% of patients. Conclusion Intra-esophageal food debris or resistance at the esophagogastric junction on upper gastrointestinal endoscopy will be positive in only about half of patients with achalasia. Other supportive diagnostic examinations, such as chest CT or barium fluoroscopy, should therefore be included in order to avoid overlooking the disease.

Background Several types of physical examinations are used in the diagnosis of meningitis, including nuchal rigidity, jolt accentuation, Kernig's sign, and Brudzinski's sign. Jolt accentuation was reported to have sensitivity of nearly 100% and to be highly efficient for excluding meningitis, but more recent studies showed that a number of patients with meningitis may present negative in this test. Methods We systematically reviewed studies on the above‐mentioned physical examination tests and performed meta‐analysis of their diagnostic characteristics to evaluate the clinical usefulness. Nine studies, comprising a total of 599 patients with pleocytosis in the cerebrospinal fluid (CSF) and 1216 patients without CSF pleocytosis, were enrolled in the analysis. Results Jolt accentuation showed a decent level of odds ratio (3.62; 99% confidence interval (CI): 1.13‐11.60, P = 0.004) comparable to that in nuchal rigidity (2.52; 1.21‐5.27, P = 0.001) for the correct prediction of CSF pleocytosis among subjects with suspected meningitis. The estimated sensitivity was relatively high (40%‐60%) in nuchal rigidity or jolt accentuation tests. On the other hand, Kernig's and Brudzinski's signs exhibited relatively low sensitivity (20%‐30%). The estimated specificity was higher in Kernig's and Brudzinski's signs (85%‐95%) than in nuchal rigidity or jolt accentuation tests (65%‐75%). Conclusion Approximately half of the patients with meningitis may not present typical meningeal signs upon physical examination. Combining several examinations for the detection of meningeal signs may decrease the risk of misdiagnosis.

Differentiated thyroid cancer (DTC) is associated with a good long-term prognosis, but bone metastases can adversely affect patients’ quality of life and survival. Stereotactic radiotherapy (SRT) can deliver high-dose irradiation to target lesions and it has been reported to be useful for various cancers. However, few studies have examined the efficacy of SRT for thyroid cancer. In the present study, the aim was to investigate the efficacy of SRT using the CyberKnife for bone metastases from DTC. From September 2013 to April 2018, SRT with the CyberKnife system was used to treat 60 bone metastases from DTC in 13 patients. The patients’ medical records were retrospectively reviewed to obtain information about the adverse events associated with SRT. Of the 60 lesions, 40 could be evaluated by follow-up CT for therapeutic effectiveness, and the RECIST criteria were used to assess the response. The cancers were papillary cancer in 3 patients, follicular cancer in 9 and poorly differentiated cancer in 1. SRT was delivered in 1–10 fractions, with a median dose of 27 Gy (range, 8–48 Gy). Adverse events were infrequent and mild. The median follow-up of the 40 lesions was 11 (range, 2–56) months. The responses were partial response in 2 lesions, stable disease in 37 lesions and progressive disease in 1 lesion, with a 1-year local control rate of 97.1%. The present study showed that SRT using the CyberKnife system was a feasible and effective treatment for bone metastases of DTC.

We present a report of a 29-year-old woman with non-dipper type refractory hypertension due to the vascular compression of the medulla oblongata. The patient was diagnosed with hypertension at 17 years of age and underwent emergency Caesarean section at 26 weeks of gestation during 2 pregnancies due to severe high blood pressure. We suspected medullary compression by the curved posterior inferior cerebellar artery as the cause of her intractable hypertension, and she underwent Jannetta's decompression surgery. After the surgery, her blood pressure swiftly decreased to almost within the normal range, and her blood pressure pattern normalized to dipper type.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization classification published in 2017. Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 2004 WHO classification. Based on the Turin criteria, 30 (40%) cases were re-classified as PDTC-Turin (+) and 45 (60%) cases were PDTC-Turin (−). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (−). Seventy-five patients (48 females and 27 males) had a median age at the time of surgery of 57 years. Preoperative diagnosis was benign in 16 (21%), follicular tumor in 40 (53%), and malignant in 19 (25%). The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 97% and 44% for PDTC-Turin (+) and 100% and 88% for PDTC-Turin (−). On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) than in the PDTC-Turin (−) (p = 0.0096, and p = 0.0016). Multivariate analysis showed that Turin criteria status, Ki-67 labeling index ≥ 10%, and age 55 ≥ years were the independent prognostic factors for recurrence. The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 2017 WHO classification reflects the prognosis more accurately than the 2004 WHO classification.

In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.

In this report, we present the successful treatment of five consecutive cases of premenopausal women suffering from severe menstrual migraine with tokishakuyakusan (TSS). Two patients were complicated by tension‐type headache (TTH), and another patient was by medication overuse headache (MOH). The effects of triptans were limited in all of them. After starting TSS, they showed dramatic improvement in the severity and frequency of their attacks. The patients with TTH and MOH also showed dramatic improvement in their symptoms. TSS could be a promising alternative choice for patients with intractable menstruation–related headaches that are refractory to conventional treatments, including triptans.

Patient: Male, 67-year-old Final Diagnosis: Pancreatic moderately differentiated tubular metastatic adenocarcinoma Symptoms: Abdominal pain • ascites Medication: — Clinical Procedure: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Specialty: Oncology • Surgery Objective: Unusual setting of medical care Background: Peritoneal metastasis is a common progression of abdominal-pelvic cancers, and it is associated with poorer oncological prognosis when compared to other metastasis sites. Its treatment has limited results, mainly because of poor bioavailability of chemotherapy within the abdominal cavity after systemic administration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proposed as a novel method to deliver chemotherapy directly into the peritoneal surface; it combines the effectiveness and response of an intraperitoneal therapy with benefits of a minimally invasive approach. The laparoscopic capnoperitoneum is used to instill chemotherapy particles in a more efficient way for distribution and penetration when compared to peritoneal lavage. In the present study, we describe the first PIPAC performed in Brazil, according to the standard technique previously described with the Capnopen® nebulizer device, as well as technique details based on our literature review. Case Report: A 67-year-old man with pancreatic adenocarcinoma metastatic to the liver at first diagnosis underwent systemic treatment with the FOLFIRINOX protocol. After a major clinical response due to systemic treatment, pancreaticoduodenectomy was performed with resection and radiofrequency ablation of hepatic nodules. After 7 months of follow-up, the patient’s condition evolved with symptomatic relapse in the peritoneum. Aiming at better control of this site, multiple PIPAC procedures were performed, showing excellent control of the perito-neal cavity disease. The patient had a sustained response in the peritoneal cavity and showed systemic disease progression 6 months after the first PIPAC procedure, which deceased at 20 months after the first PIPAC procedure and 42 months after the primary diagnosis. Conclusions: This report shows that the PIPAC procedure is reproducible elsewhere, with safety and good functional results.

Background: The characteristics of pediatric differentiated thyroid cancer (DTC) are substantially different from those of adult DTC. This study investigated whether the cutoff age of 18 years, as ...

We sought to investigate the effects of resistance training (RT) combined with erythropoietin (EPO) and iron sulfate on the hemoglobin, hepcidin, ferritin, iron status, and inflammatory profile in older individuals with end-stage renal disease (ESRD). ESRD patients (n: 157, age: 66.8 ± 3.6, body mass: 73 ± 15, body mass index: 27 ± 3), were assigned to control (CTL, n: 76) and exercise groups (RT, n: 81). The CTL group was divided according to the iron treatment received: without iron treatment (CTL—none, n = 19), treated only with iron sulfate or EPO (CTL—EPO or IRON, n = 19), and treated with both iron sulfate and EPO (CTL—EPO + IRON, n = 76). The RT group followed the same pattern: (RT—none, n = 20), (RT—EPO or IRON, n = 18), and (RT—EPO + IRON, n = 86). RT consisted of 24 weeks/3 days per week at moderate intensity of full-body resistance exercises prior to the hemodialysis section. The RT group, regardless of the iron treatment, improved iron metabolism in older individuals with ESRD. These results provide some clues on the effects of RT and its combination with EPO and iron sulfate in this population, highlighting RT as an important coadjutant in ESRD-iron deficiency.

Necroptosis is a pivotal process in cancer biology, however, the clinical significance of necroptosis in esophageal squamous cell carcinoma (ESCC) has remained unknown. Therefore, in this study, we aimed to verify the potential involvement of necroptosis in the clinical outcome, chemotherapeutic resistance, and tumor microenvironment of ESCC. Mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunohistochemically examined in 88 surgically resected specimens following neoadjuvant chemotherapy (NAC) and 53 pre-therapeutic biopsy specimens, respectively. Tumor-infiltrating lymphocytes (TILs) were also evaluated by immunolocalizing CD3, CD8, and forkhead box protein 3 (FOXP3) in the residual tumors after NAC. High pMLKL status in the post-NAC resected specimens was significantly correlated with worse prognosis in ESCC patients. Multivariate analysis demonstrated that a high pMLKL status was an independent prognostic factor. In pre-NAC biopsy specimens, a high pMLKL status was significantly associated with a lower therapeutic efficacy. CD8+ TILs were significantly lower in the high-pMLKL group. FOXP3+ TILs were significantly higher in both high-MLKL and high-pMLKL groups. We first demonstrated pMLKL status as an independent prognostic factor in ESCC patients. Our study revealed the possible involvement of necroptosis in the immunosuppressive microenvironment, resulting in the attenuated therapeutic efficacy of NAC and eventual adverse clinical outcomes in ESCC.

Purpose There is no sufficient data about the clinical course and outcome in thyroid cancer patients who become pregnant after diagnosis of distant metastasis (DM). The current study was conducted to collect information regarding the clinical and reproductive characteristics, and outcomes in thyroid cancer patients who became pregnant after being diagnosed with DM. Methods Records of 125 differentiated thyroid cancer (DTC) patients with age ≤ 45 years at DM diagnosis who had visited Ito Hospital from January 2005 to June 2021 were retrospectively reviewed. Among those 125 patients, 28 who became pregnant after DM diagnosis were classified as pregnant group, and the remained 97 patients were classified as comparator group. Results In pregnant group, the median age at malignancy diagnosis, DM diagnosis, and first pregnancy after DM diagnosis was 25 years (range, 4–41 years), 27 years (range, 11–41 years), and 32 years (range, 25–45 years), respectively. Fifty-five pregnancies and 40 live births were reported. Three patients had live births by embryo transfer. Other pregnancy outcomes were miscarriage (n = 14) and induced abortion (n = 1). No one died during the follow-up period in this study. The 10-year progression free survival (PFS) rates of pregnant and comparator group were 92.1% and 74.4%, respectively. Conclusion DTC patients who became pregnant after DM diagnosis had good survival. Our results add to the information required for counseling thyroid cancer patients who have concerns about their fertility in the future.