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1.
Surg Today ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502210

RESUMO

PURPOSE: This study evaluated the risk of metachronous colorectal cancer (CRC) after resection of index (first) rectal cancer in patients with Lynch syndrome (LS). METHODS: Clinicopathological data of patients with genetically proven LS were retrospectively analyzed in this multicenter Japanese study. The cumulative incidence of metachronous CRC and the overall survival were compared between patients with index rectal cancer (rectal group) and those with index colon cancer (colon group). RESULTS: The median age at index CRC surgery was lower in the rectal group than in the colon group (37 vs. 46 years old, P = 0.01). The cumulative 5-, 10-, and 20-year incidences of metachronous CRC were 3.5%, 13.9%, and 21.1%, respectively, in the rectal cancer group and 14.9%, 22.0%, and 57.9%, respectively, in the colon cancer group (P = 0.02). The overall survival curves were not significantly different between two groups (P = 0.23). CONCLUSION: This is the first report from an East Asian country to report the risk of metachronous CRC after resection of index rectal cancer in patients with LS. Despite this study having several limitations, we cannot recommend extended resection, such as total proctocolectomy, for index rectal cancer as a standard surgical treatment in patients with LS.

2.
Cancer Sci ; 114(12): 4596-4606, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37798255

RESUMO

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.


Assuntos
Polipose Adenomatosa do Colo , Fibromatose Agressiva , Neoplasias Gástricas , Humanos , Genes APC , Fibromatose Agressiva/genética , Genótipo , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Fenótipo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Estudos de Associação Genética , Mutação
3.
Int J Clin Oncol ; 28(12): 1633-1640, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37752370

RESUMO

BACKGROUND: We evaluated the risk of metachronous colorectal cancer (mCRC) and explored the optimal extent of colectomy in patients with Lynch syndrome (LS) and first colon cancer (fCC) in Japan, where the extent of colectomy for colon cancer (CC) is shorter than that in Western countries. METHODS: The clinicopathologic and survival data of patients with LS who developed CC were collected from a nationwide database and analyzed retrospectively. The cumulative incidence of mCRC after actual segmental colectomy was compared with that of mCRC when more extensive colectomy was assumed. RESULTS: There were 142 eligible patients (65 female). The median age at fCC surgery was 46.5 (range: 14-80) years. The cumulative incidence of 5-, 10-, and 20-year mCRC rate was 13.4%, 20.8%, and 53.6%, respectively. The incidence was higher in the left-sided group (splenic flexure to rectosigmoid colon, n = 54) than in the right-sided group (cecum to transvers colon, n = 88) (66.3% vs. 45.3% in 20 years, P < 0.01). Assuming that all patients would have undergone hemicolectomy or total colectomy, the estimated mCRC risk was 41.5% and 9.4% (P < 0.01, vs. actual procedures), respectively. The 20-year overall survival rate of all the patients was 83.3% without difference by fCC sidedness (P = 0.38). CONCLUSIONS: To reduce the incidence of mCRC, patients with genetically diagnosed LS and fCC, preferentially located in the left-sided colon, may need to undergo more extended colectomy than that usually performed in Japan. However, such extended colectomy should be counterbalanced with favorable overall survival and actual risk of mCRC development.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais Hereditárias sem Polipose , Segunda Neoplasia Primária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Colectomia/efeitos adversos , Colectomia/métodos , Neoplasias do Colo/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Japão/epidemiologia , Segunda Neoplasia Primária/patologia , Estudos Retrospectivos , Masculino
4.
Front Oncol ; 13: 1205847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601671

RESUMO

Genetic testing of the APC gene by sequencing analysis and MLPA is available across commercial laboratories for the definitive genetic diagnosis of familial adenomatous polyposis (FAP). However, some genetic alterations are difficult to detect using conventional analyses. Here, we report a case of a complex genomic APC-TP63 rearrangement, which was identified in a patient with FAP by a series of genomic analyses, including multigene panel testing, chromosomal analyses, and long-read sequencing. A woman in her thirties was diagnosed with FAP due to multiple polyps in her colon and underwent total colectomy. Subsequent examination revealed fundic gland polyposis. No family history suggesting FAP was noted except for a first-degree relative with desmoid fibromatosis. The conventional APC gene testing was performed by her former doctor, but no pathogenic variant was detected, except for 2 variants of unknown significance. The patient was referred to our hospital for further genetic analysis. After obtaining informed consent in genetic counseling, we conducted a multigene panel analysis. As insertion of a part of the TP63 sequence was detected within exon16 of APC, further analyses, including chromosomal analysis and long-read sequencing, were performed and a complex translocation between chromosomes 3 and 5 containing several breakpoints in TP63 and APC was identified. No phenotype associated with TP63 pathogenic variants, such as split-hand/foot malformation (SHFM) or ectrodactyly, ectodermal dysplasia, or cleft lip/palate syndrome (EEC) was identified in the patient or her relatives. Multimodal genomic analyses should be considered in cases where no pathogenic germline variants are detected by conventional genetic testing despite an evident medical or family history of hereditary cancer syndromes.

6.
Neurol Med Chir (Tokyo) ; 63(9): 432-435, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37423753

RESUMO

Insertion of a deep brain stimulating electrode is a commonly performed procedure. Burr hole caps play an important role in this procedure by immobilizing this electrode; however, burr hole caps could form scalp bumps, which can create further complications. The dual-floor burr hole technique could prevent the formation of scalp bumps. This technique has previously been used with older versions of burr hole caps and has proved to be successful. In recent years, modern burr hole caps with an internal electrode locking mechanism have become the mainstay for this procedure. However, modern burr hole caps differ considerably in diameter and shape from older burr hole caps. In the present study, a dual-floor burr hole technique was performed using modern burr hole caps. To accommodate the increase in diameters and changes in the shape of modern burr hole caps, a perforator with a 30-mm diameter was used for shaving the bone, and the bone shaving depth was altered. This surgical technique was applied to 23 consecutive deep brain stimulation surgeries without complications and was thus positively optimized for modern burr hole caps.


Assuntos
Estimulação Encefálica Profunda , Trepanação , Humanos , Trepanação/métodos , Encéfalo , Eletrodos , Estimulação Encefálica Profunda/métodos , Couro Cabeludo
7.
Front Syst Neurosci ; 17: 1130272, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388942

RESUMO

This study aimed to clarify whether short-term neurofeedback training during the acute stroke phase led to prefrontal activity self-regulation, providing positive efficacy to working memory. A total of 30 patients with acute stroke performed functional near-infrared spectroscopy-based neurofeedback training for a day to increase their prefrontal activity. A randomized, Sham-controlled, double-blind study protocol was used comparing working memory ability before and after neurofeedback training. Working memory was evaluated using a target-searching task requiring spatial information retention. A decline in spatial working memory performance post-intervention was prevented in patients who displayed a higher task-related right prefrontal activity during neurofeedback training compared with the baseline. Neurofeedback training efficacy was not associated with the patient's clinical background such as Fugl-Meyer Assessment score and time since stroke. These findings demonstrated that even short-term neurofeedback training can strengthen prefrontal activity and help maintain cognitive ability in acute stroke patients, at least immediately after training. However, further studies investigating the influence of individual patient clinical background, especially cognitive impairment, on neurofeedback training is needed. Current findings provide an encouraging option for clinicians to design neurorehabilitation programs, including neurofeedback protocols, for acute stroke patients.

8.
Digestion ; 104(5): 335-347, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37054692

RESUMO

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.


Assuntos
Endoscopia por Cápsula , Síndrome de Peutz-Jeghers , Adolescente , Humanos , Adulto , Criança , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/terapia , Qualidade de Vida , Pólipos Intestinais/patologia , Intestino Delgado/patologia
9.
Neurol Med Chir (Tokyo) ; 63(4): 137-140, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36682793

RESUMO

Stereotactic neurosurgery is an established technique, but it has several limitations. In frame-based stereotaxy using a stereotactic frame, frame setting errors may decrease the accuracy of the procedure. Frameless stereotaxy using neuronavigation requires surgeons to shift their view from the surgical field to the navigation display and to advance the needle while assuming a physically uncomfortable position. To overcome these limitations, several researchers have applied augmented reality in stereotactic neurosurgery. Augmented reality enables surgeons to visualize the information regarding the target and preplanned trajectory superimposed over the actual surgical field. In frame-based stereotaxy, a researcher applies tablet computer-based augmented reality to check for the setting errors of the stereotactic frame, thereby improving the safety of the procedure. Several researchers have reported performing frameless stereotaxy guided by head-mounted-display-based augmented reality that enables surgeons to advance the needle at a more natural posture. These studies have shown that augmented reality can address the limitations of stereotactic neurosurgery. Conversely, they have also revealed the limited accuracy of current augmented reality systems for small targets, which indicates that further development of augmented reality systems is needed.


Assuntos
Realidade Aumentada , Neurocirurgia , Cirurgia Assistida por Computador , Humanos , Procedimentos Neurocirúrgicos/métodos , Neuronavegação/métodos , Cirurgia Assistida por Computador/métodos , Técnicas Estereotáxicas
10.
Gastrointest Endosc ; 97(1): 59-68.e7, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36084716

RESUMO

BACKGROUND AND AIMS: In familial adenomatous polyposis (FAP), neoplastic lesions outside the colon have become increasingly important. The genotype-phenotype correlation has been established for duodenal polyps, and regular screening is recommended. However, this correlation remains unclear for small-intestinal lesions, except for reports on the relationship between their occurrence and Spigelman stage. Here, we used small-bowel capsule endoscopy (SBCE) to investigate the genotype-phenotype correlation of small-intestinal polyps in FAP. METHODS: The genotype-phenotype correlation of small-intestinal polyps was investigated in patients with FAP who underwent SBCE, Esophagogastroduodenoscopy (EGD), and adenomatous polyposis coli (APC) gene analysis. Of 64 patients with FAP who underwent SBCE, 41 were included in the final analysis, 4 did not undergo a complete small intestine examination, and 19 did not undergo genetic analysis. RESULTS: The prevalence (median number) of small-intestinal polyps by Spigelman stage was 26% (1.5), 0% (0), 44% (5), 60% (4), and 73% (25.5) for stages 0 to IV, respectively. Significantly more small-intestinal polyps were found in Spigelman stage III and IV groups than in the stage 0 group (P < .05). The APC variant was negative for 6 patients (15%), and the sites associated with more than 5 small-intestinal polyps were codons 278, 1062, 1114, 1281, 1307, 1314, and 1504. CONCLUSIONS: In FAP patients, SBCE surveillance is potentially recommended for patients with pathogenic variants in the APC gene at codons 278 and 1062 to 1504 or with Spigelman stage III or higher.


Assuntos
Polipose Adenomatosa do Colo , Endoscopia por Cápsula , Hamartoma , Humanos , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/genética , Pólipos Intestinais/patologia , Intestino Delgado/patologia , Códon , Hamartoma/patologia , Estudos de Associação Genética
11.
J Gene Med ; 25(1): e3457, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36278965

RESUMO

BACKGROUND: The delivery of adeno-associated virus (AAV) vectors via the cerebrospinal fluid (CSF) has emerged as a valuable method for widespread transduction in the central nervous system. Although infusion into the cerebral ventricles is a common protocol in preclinical studies of small animals, the cisterna magna has been recognized as an alternative target for clinical studies because it can be reached in a less invasive manner using an intrathecal catheter via the subarachnoid space from a lumbar puncture. METHODS: We evaluated the early distribution of fluorine-18-labeled AAV9 vectors infused into the lateral ventricle or cisterna magna of four non-human primates using positron emission tomography. The expression of the green fluorescent protein was immunohistochemically determined. RESULTS: In both approaches, the labeled vectors diffused into the broad arachnoid space around the brain stem and cervical spinal cord within 30 min. Both infusion routes efficiently transduced neurons in the cervical spinal cord. CONCLUSIONS: For gene therapy that primarily targets the cervical spinal cord and brainstem, such as amyotrophic lateral sclerosis, cisterna magna infusion would be a feasible and effective administration method.


Assuntos
Terapia Genética , Medula Espinal , Animais , Transdução Genética , Medula Espinal/metabolismo , Terapia Genética/métodos , Primatas/genética , Vetores Genéticos/genética , Dependovirus/genética
12.
Endoscopy ; 55(4): 344-352, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36216266

RESUMO

BACKGROUND: Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. METHOD: A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. RESULTS: 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %). CONCLUSION: IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed.


Assuntos
Polipose Adenomatosa do Colo , Pólipos , Humanos , Estudos Prospectivos , Polipose Adenomatosa do Colo/cirurgia , Reto/cirurgia , Colectomia/métodos , Pólipos/cirurgia
13.
Case Rep Oncol ; 15(2): 792-797, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157696

RESUMO

A 24-year-old woman suspected of Lynch syndrome was found to carry a BRCA1 pathogenic variant, based on germline multigene panel testing (MGPT). The patient was diagnosed with endometrial carcinoma and underwent modified radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and omentectomy at the age of 23. Based on her father's history of colorectal cancer and her history of early onset endometrial cancer, mismatch repair protein immunohistochemistry analysis was performed. However, no loss of expression for mismatch repair proteins was found. Given her family history of ovarian and breast cancers, MGPT was recommended to identify the presence of any hereditary tumor syndromes. This testing revealed a BRCA1 pathogenic variant (exon13: c.1016delA, p.Lys339ArgfsX2) and diagnosed as hereditary breast and ovarian cancer syndrome (HBOC). Subsequently, the patient's mother also underwent single-site analysis for this variant, and the same pathogenic variant was detected. The patient and her mother are at high risk of developing BRCA1-associated HBOC-related cancers. Based on family history, clinical surveillance is currently underway for this patient and her mother. Currently, MGPT offers the potential for comprehensive genetic cancer risk assessment and may provide a more rational approach for the genetic assessment of those individuals whose personal and family cancer histories do not fit neatly into a single syndrome. This case suggests that if a patient is at high risk for hereditary tumor syndromes, MGPT should be considered to improve disease management strategies in clinical settings.

14.
JGH Open ; 6(4): 257-262, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35475204

RESUMO

Background and Aim: This study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features. Methods: We retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed. Results: A total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B-cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa-associated lymphoid tissue (MALT) lymphoma (9%), peripheral T-cell lymphoma-NOS (2%), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine. Conclusions: Colorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types.

16.
Int J Clin Oncol ; 27(2): 265-280, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34973107

RESUMO

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).


Assuntos
Preservação da Fertilidade , Neoplasias , Oncologistas , Adolescente , Criança , Feminino , Humanos , Japão , Oncologia , Neoplasias/terapia , Adulto Jovem
17.
Int J Clin Oncol ; 27(2): 281-300, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35022887

RESUMO

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.


Assuntos
Preservação da Fertilidade , Neoplasias , Oncologistas , Adolescente , Criança , Humanos , Japão , Oncologia , Neoplasias/terapia , Adulto Jovem
18.
Nat Aging ; 2(2): 105-114, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-37117756

RESUMO

Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3ß-hydroxyl-steroid dehydrogenase (3ß-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3ß-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3ß-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3ß-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction.


Assuntos
Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Feminino , Humanos , NAD , Glândulas Tarsais , Lágrimas/fisiologia , Esteroides , Hormônios
19.
Surg Endosc ; 36(1): 515-525, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33569725

RESUMO

BACKGROUND AND AIMS: Colorectal neoplastic lesions (≥ 20 mm) are commonly treated via piecemeal endoscopic mucosal resection (p-EMR) but have a high rate of local recurrence. We aimed to clarify the optimal surveillance interval after p-EMR for these neoplasias. METHODS: In this multicenter (15 participating institutions) prospective, randomized trial, 180 patients recruited over a 4-year period and were classified based on tumor location, tumor diameter, histological diagnosis, institution, and number of resected specimens. The patients underwent curative p-EMR followed by scheduled surveillance colonoscopy at 3, 6, 12, and 24 months after p-EMR (group A; n = 90) or at 6, 12, and 24 months after p-EMR (group B; n = 90). The primary endpoint was cumulative local recurrence at 6 months after p-EMR. Secondary endpoints included local recurrence and the cumulative surgical resection rate of recurrent tumors during the 24-month follow-up period. RESULTS: The median tumor diameter was 25 mm (IQR 20-30). Six months after p-EMR, 12 and 6 local recurrences were noted in groups A and B, which corresponded to 13 and 8 recurrences, respectively, during the 24-month surveillance period. The primary and secondary endpoints of recurrence were not significantly different between the groups on either intention-to-treat or per-protocol analysis; no surgery case was observed in group B when a strict surveillance protocol of 6-, 12-, and 24-month follow-up post-EMR was followed. CONCLUSIONS: For patients who underwent p-EMR for neoplastic lesions, additional postprocedural 3-month surveillance did not show superior results in detecting recurrence compared with a 6-month surveillance interval. CLINICAL TRIAL REGISTRATION: UMIN000015740.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Colonoscopia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Resultado do Tratamento
20.
J Clin Neurosci ; 94: 305-314, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34863455

RESUMO

To date, several researchers have introduced augmented reality navigation (ARN) into neurological surgery. While its application in brain tumor surgery seems promising, reports on its utility have been limited, thus warranting further evaluation. To clarify the stages and approaches in which ARN is useful and assess the effect of presurgical discussion with surgeons, we assessed usefulness using a hand-held ARN system we had developed, which displays three-dimensional (3D) virtual structures overlaid on a real-time image of the surgical field via a tablet PC monitor. The system was tested in 20 patients undergoing various procedures, with the first 10 consecutive cases being unselected and the following 10 cases being selected, for whom 3D models were prepared per the surgeons' request. Thereafter, the surgeons ranked its usefulness during each stage of surgery. Consequently, case selection and presurgical discussions with surgeons considerably improved the usefulness, with the "useful" gradings improving from 50% to 88% across all surgical stages. Accordingly, usefulness improved from 50% to 90%, 67% to 100%, and 40% to 80% during the skin incision and craniotomy, dura incision, and intradural procedure stages, respectively. ARN was useful for superficial tumor resection, but less so for deep-seated tumor resection, except when using the transcortical and interhemispheric approaches. In conclusion, a tablet-type ARN can be useful during skin incisions, craniotomy and dura incisions, superficial tumor resections, and transcortical and interhemispheric approaches for deep-seated tumors. Case selection and presurgical discussions with surgeons were essential for the efficacy of ARN.


Assuntos
Realidade Aumentada , Neoplasias Encefálicas , Neurocirurgia , Cirurgia Assistida por Computador , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Humanos , Procedimentos Neurocirúrgicos
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