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BACKGROUND: Recurrent acute cholecystitis (RAC) can occur after non-surgical treatment for acute cholecystitis (AC), and can be more severe in comparison to the first episode of AC. Low skeletal muscle mass or adiposity have various effects in several diseases. We aimed to clarify the relationship between RAC and body parameters. METHODS: Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled. The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC. The areas were divided by height to obtain the psoas muscle mass index (PMI) and subcutaneous/visceral adipose tissue index (SATI/VATI). According to median VATI, SATI and PMI values by sex, patients were divided into the high and low PMI groups. We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC. RESULTS: The entire cohort was divided into the high PMI (n = 81) and low PMI (n = 80) groups. In the propensity score-matched cohort there were 57 patients in each group. In Kaplan-Meier analysis, the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts (log-rank P = 0.001 and 0.015, respectively). In a multivariate Cox regression analysis, the hazard ratios of low PMI and low VATI for RAC were 5.250 (95% confidence interval 1.083-25.450, P = 0.039) and 0.158 (95% confidence interval: 0.026-0.937, P = 0.042), respectively. CONCLUSIONS: Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.
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Colecistite Aguda , Sarcopenia , Humanos , Prognóstico , Estudos de Coortes , Adiposidade , Pontuação de Propensão , Músculos Psoas/patologia , Estudos Retrospectivos , Músculo Esquelético/diagnóstico por imagemRESUMO
Here, we report the application of a long-read sequencer, PromethION, for analyzing human cancer genomes. We first conducted whole-genome sequencing on lung cancer cell lines. We found that it is possible to genotype known cancerous mutations, such as point mutations. We also found that long-read sequencing is particularly useful for precisely identifying and characterizing structural aberrations, such as large deletions, gene fusions, and other chromosomal rearrangements. In addition, we identified several medium-sized structural aberrations consisting of complex combinations of local duplications, inversions, and microdeletions. These complex mutations occurred even in key cancer-related genes, such as STK11, NF1, SMARCA4, and PTEN The biological relevance of those mutations was further revealed by epigenome, transcriptome, and protein analyses of the affected signaling pathways. Such structural aberrations were also found in clinical lung adenocarcinoma specimens. Those structural aberrations were unlikely to be reliably detected by conventional short-read sequencing. Therefore, long-read sequencing may contribute to understanding the molecular etiology of patients for whom causative cancerous mutations remain unknown and therapeutic strategies are elusive.
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Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Genes Neoplásicos , Sequenciamento Completo do Genoma/métodos , Linhagem Celular Tumoral , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Rearranjo Gênico , Técnicas de Genotipagem , Humanos , Masculino , Mutação , Transcrição GênicaRESUMO
Long-read whole-genome sequencing analysis of DNA methylation would provide useful information on the chromosomal context of gene expression regulation. Here we describe the development of a method that improves the read length generated by using the bisulfite-sequencing-based approach. In this method, we combined recently developed enzymatic base conversion, where an unmethylated cytosine (C) should be converted to thymine (T), with nanopore sequencing. After methylation-sensitive base conversion, the sequencing library was constructed using long-range polymerase chain reaction. This type of analysis is possible using a minimum of 1 ng genomic DNA, and an N50 read length of 3.4-7.6 kb is achieved. To analyze the produced data, which contained a substantial number of base mismatches due to sequence conversion and an inaccurate base read of the nanopore sequencing, a new analytical pipeline was constructed. To demonstrate the performance of long-read methylation sequencing, breast cancer cell lines and clinical specimens were subjected to analysis, which revealed the chromosomal methylation context of key cancer-related genes, allele-specific methylated genes, and repetitive or deletion regions. This method should convert the intractable specimens for which the amount of available genomic DNA is limited to the tractable targets.
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Metilação de DNA , DNA/genética , Genoma Humano/genética , Sequenciamento por Nanoporos/métodos , Reação em Cadeia da Polimerase/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ilhas de CpG/genética , DNA/química , Humanos , Sulfitos/química , Sequenciamento Completo do Genoma/métodosRESUMO
We present a case of fetal atrioventricular block, heterotaxy, and ventricular noncompaction observed longitudinally from the first to early second trimesters using B-mode and Doppler imaging, including superb microvascular imaging. At 12 weeks of gestation, the atrial and ventricular rates were 133 and 67 beats/min, respectively, and dextrocardia was noted. At 15 weeks of gestation, detailed sonography revealed ventricular septal defect, interruption of the inferior vena cava, dilated azygos vein, and double-outlet right ventricle. In addition, superb microvascular imaging revealed irregular contours in the anatomical left ventricular wall, indicating prominent trabeculations of the ventricle, which were characteristic findings of ventricular noncompaction. At 21 weeks of gestation, intrauterine fetal death occurred, and the autopsy revealed complex congenital heart disease, including ventricular noncompaction.
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Bloqueio Atrioventricular , Comunicação Interventricular , Síndrome de Heterotaxia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Síndrome de Heterotaxia/complicações , Síndrome de Heterotaxia/diagnóstico por imagem , Humanos , Gravidez , Ultrassonografia Pré-Natal/métodosRESUMO
Cancer is a disease largely caused by genomic aberrations. Utilizing many rapidly emerging sequencing technologies, researchers have studied cancer genomes to understand the molecular statuses of cancer cells and to reveal their vulnerabilities, such as driver mutations or gene expression. Long-read technologies enable us to identify and characterize novel types of cancerous mutations, including complicated structural variants in haplotype resolution. In this review, we introduce three representative platforms for long-read sequencing and research trends of cancer genomics with long-read data. Further, we describe that aberrant transcriptome and epigenome statuses, namely, fusion transcripts, as well as aberrant transcript isoforms and the phase information of DNA methylation, are able to be elucidated by long-read sequencers. Long-read sequencing may shed light on novel types of aberrations in cancer genomics that are being missed by conventional short-read sequencing analyses.
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Sequenciamento de Cromatina por Imunoprecipitação/métodos , Genômica/métodos , Genômica/tendências , Neoplasias/genética , RNA-Seq/métodos , Sequenciamento de Cromatina por Imunoprecipitação/tendências , Metilação de DNA , Epigenoma , Haplótipos , Humanos , Isoformas de Proteínas/genética , RNA-Seq/tendências , Transcriptoma/genéticaRESUMO
BACKGROUND: Genome graph is an emerging approach for representing structural variants on genomes with branches. For example, representing structural variants of cancer genomes as a genome graph is more natural than representing such genomes as differences from the linear reference genome. While more and more structural variants are being identified by long-read sequencing, many of them are difficult to visualize using existing structural variants visualization tools. To this end, visualization method for large genome graphs such as human cancer genome graphs is demanded. RESULTS: We developed MOdular Multi-scale Integrated Genome graph browser, MoMI-G, a web-based genome graph browser that can visualize genome graphs with structural variants and supporting evidences such as read alignments, read depth, and annotations. This browser allows more intuitive recognition of large, nested, and potentially more complex structural variations. MoMI-G has view modules for different scales, which allow users to view the whole genome down to nucleotide-level alignments of long reads. Alignments spanning reference alleles and those spanning alternative alleles are shown in the same view. Users can customize the view, if they are not satisfied with the preset views. In addition, MoMI-G has Interval Card Deck, a feature for rapid manual inspection of hundreds of structural variants. Herein, we describe the utility of MoMI-G by using representative examples of large and nested structural variations found in two cell lines, LC-2/ad and CHM1. CONCLUSIONS: Users can inspect complex and large structural variations found by long-read analysis in large genomes such as human genomes more smoothly and more intuitively. In addition, users can easily filter out false positives by manually inspecting hundreds of identified structural variants with supporting long-read alignments and annotations in a short time. SOFTWARE AVAILABILITY: MoMI-G is freely available at https://github.com/MoMI-G/MoMI-G under the MIT license.
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Genoma Humano , Software , Navegador , Alelos , Linhagem Celular , Diploide , Variação Estrutural do Genoma , Humanos , Interface Usuário-ComputadorRESUMO
AIM: To investigate the natural history of fetal ovarian cysts and elucidate the risk factors for postnatal adverse outcomes in fetal ovarian cysts. METHODS: The study subjects were 18 cases with ovarian cysts prenatally diagnosed using ultrasonography at our hospital between 2007 and 2020. The subjects were classified by cyst characteristics according to echogenic patterns [simple cyst (S) and complex cyst (C)], changes in echogenic patterns (S-to-S, S-to-C, and C-to-C), and diameters (<40 and ≥ 40 mm). Clinical parameters and outcomes were compared between S and C patterns, S-to-S and S-to-C patterns, and <40 and ≥ 40 mm diameters. RESULTS: Cases with S and C patterns (15 and 3, respectively) had median gestational ages of 35 and 36 weeks, respectively, and maximum cyst diameters of 36 and 57mm, respectively. The number of cases with S-to-S, S-to-C and C-to-C patterns were 11, 4 and 3, respectively. The maximum cyst diameter in cases with S-to-C patterns (58 mm) was larger than that in cases with S-to-S patterns (34 mm) (P<0.05). Placental weight in cases with cysts >40 mm and/or cyst expansion was greater than that in cases with neither or both conditions (P<0.05). Spontaneous resolution (before and after birth) occurred in 8 of 9 and 3 of 9 cases with maximum cyst diameters <40 and ≥ 40 mm, respectively. Ovarian function was lost in 2 cases with S-to-C patterns and in 2 cases with C-to-C patterns. CONCLUSION: Cases with cyst diameters ≥ 40 mm and/or cyst expansion during the late third trimester had greater placental weight and more postnatal adverse outcomes.
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Idade Gestacional , Cistos Ovarianos , Ultrassonografia Pré-Natal , Humanos , Feminino , Cistos Ovarianos/diagnóstico por imagem , Gravidez , Fatores de Risco , Adulto , Recém-Nascido , Doenças Fetais/diagnóstico por imagem , Estudos Retrospectivos , Resultado da GravidezRESUMO
A liver cyst is hepatic fluid-filled cavities often detected in clinical surveillances such as a health examination. Although the liver cyst is usually asymptomatic and observed without any therapeutic intervention, it can be symptomatic and needs treatment due to its enlargement, hemorrhage, and infection. A 74-year-old woman presented with upper abdominal pain and a huge liver cyst in the left lobe. Several examinations including image findings revealed that the symptom could be derived from the liver cyst. Although there is no definite guideline of treatment for symptomatic liver cysts, percutaneous ultrasound-guided drainage with sclerotherapy or surgery is often selected. Because of anatomical accessibility to the liver cyst and the patient's wish, we performed endoscopic transgastric drainage with insertion of both an internal stent and an external nasocystic tube. Sclerotherapy with minocycline hydrochloride was performed through the nasocystic tube, and the liver cyst shrunk completely without any complications. This is the first reported method of administering minocycline hydrochloride through a nasocystic tube, which can be a therapeutic option for patients with symptomatic liver cysts.
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Long-read sequencing technologies enable us to precisely identify structural variants (SVs), which would be occasionally associated with various types of diseases, including cancers. In this section, we introduce experimental and computational procedures for conducting long-read whole-genome sequencing (WGS) of cancer genomes from fresh frozen tissues/cells. We also demonstrate the analysis of SVs in cancer genomes using long-read WGS data from lung cancer cell lines by several representative computational tools, such as cuteSV and Sniffles2, as examples.
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Nanoporos , Neoplasias , Genoma , Sequenciamento Completo do Genoma/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Neoplasias/genéticaRESUMO
The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints.
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Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Pulmão/patologia , Adenocarcinoma in Situ/genética , Mutação , Microambiente TumoralRESUMO
In recent years, DNA methylation research has been accelerated by the advent of nanopore sequencers. However, read length has been limited by the constraints of base conversion using the bisulfite method, making analysis of chromatin content difficult. The read length of the previous method combining bisulfite conversion and long-read sequencing was ~1.5 kb, even using targeted PCR. In this study, we have improved read length (~5 kb), by converting unmethylated cytosines to uracils with APOBEC enzymes, to reduce DNA fragmentation. The converted DNA was then sequenced using a PromethION nanopore sequencer. We have also developed a new analysis pipeline that accounts for base conversions, which are not present in conventional nanopore sequencing, as well as errors produced by nanopore sequencing.
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Chromosomal backgrounds of cancerous mutations still remain elusive. Here, we conduct the phasing analysis of non-small cell lung cancer specimens of 20 Japanese patients. By the combinatory use of short and long read sequencing data, we obtain long phased blocks of 834 kb in N50 length with >99% concordance rate. By analyzing the obtained phasing information, we reveal that several cancer genomes harbor regions in which mutations are unevenly distributed to either of two haplotypes. Large-scale chromosomal rearrangement events, which resemble chromothripsis events but have smaller scales, occur on only one chromosome, and these events account for the observed biased distributions. Interestingly, the events are characteristic of EGFR mutation-positive lung adenocarcinomas. Further integration of long read epigenomic and transcriptomic data reveal that haploid chromosomes are not always at equivalent transcriptomic/epigenomic conditions. Distinct chromosomal backgrounds are responsible for later cancerous aberrations in a haplotype-specific manner.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Genoma Humano/genética , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Mutação , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNARESUMO
In recent years, the so-called long-read sequencing technology has had a substantial impact on various aspects of genome sciences. Here, we introduce recent studies of cancerous structural variants (SVs) using long-read sequencing technologies, namely Pacific Biosciences (PacBio) sequencers, Oxford Nanopore Technologies (ONT) sequencers, and linked-read methods. By taking advantage of long-read lengths, these technologies have enabled the precise detection of SVs, including long insertions by transposable elements, such as LINE-1. In addition to SV detection, the epigenome status (including DNA methylation and haplotype information) surrounding SV loci has also been unveiled by long-read sequencing technologies, to identify the effects of SVs. Among the various research fields in which long-read sequencing has been applied, cancer genomics has shown the most remarkable advances. In fact, many studies are beginning to shed light on the detection of SVs and the elucidation of their complex structures in various types of cancer. In the particular case of cancers, we summarize the technical limitations of the application of this technology to the analysis of clinical samples. We will introduce recent achievements from this viewpoint. However, a similar approach will be started for other applications in the near future. Therefore, by complementing the current short-read sequencing analysis, long-read sequencing should reveal the complex nature of human genomes in their healthy and disease states, which will open a new opportunity for a better understanding of disease development and for a novel strategy for drug development.
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Here, we review single-cell sequencing techniques for individual and multiomics profiling in single cells. We mainly describe single-cell genomic, epigenomic, and transcriptomic methods, and examples of their applications. For the integration of multilayered data sets, such as the transcriptome data derived from single-cell RNA sequencing and chromatin accessibility data derived from single-cell ATAC-seq, there are several computational integration methods. We also describe single-cell experimental methods for the simultaneous measurement of two or more omics layers. We can achieve a detailed understanding of the basic molecular profiles and those associated with disease in each cell by utilizing a large number of single-cell sequencing techniques and the accumulated data sets.
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Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Célula Única/métodos , Animais , Biologia Computacional/métodos , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Heterogeneidade Genética , Genômica/normas , Humanos , Proteômica/métodos , Reprodutibilidade dos Testes , Análise de Célula Única/normas , TranscriptomaRESUMO
METHODS: Subjects were 239 patients with colorectal cancer who underwent curative resection surgery from December 1994 to March 1997(Stage I-III b). The patients were given 5'-DFUR for postoperative 10 months as scheduled. They had been allocated into either a 1-year group or a 3-year group by dynamic randomization. 5'-DFUR was administered by an intermittent regimen such as 1,200 mg/body/day for five days followed by two days rest. All patients were followed for five years at least. RESULTS: 239 patients were enrolled in the study. Favorable prognoses in both groups were observed. Although no statistically significant differences in overall survival curves of full analysis set based on the drug administration durations, were detected(log-rank test, p=0.734), a better prognosis was found in the 3-year group(5-year OS: 92.0%; 1- year group, 91.4%; 3-year group). Adverse drug reactions resulted in low rates such as 14.8% in the 1-year group and 19.5% in the 3-year group. Grade 3 was found in either group. CONCLUSIONS: Due to a result in the present study that 5-year survival rates in both groups were far higher than anticipated, we could not finally clarify the optimal administration duration of 5'-DFUR. However, the results of the present study indicate that 5'-DFUR results in a good prognosis for colorectal cancer patients and is safe over a long / administration period.
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Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Floxuridina/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Floxuridina/efeitos adversos , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
The current RNA-Seq method analyses fragments of mRNAs, from which it is occasionally difficult to reconstruct the entire transcript structure. Here, we performed and evaluated the recent procedure for full-length cDNA sequencing using the Nanopore sequencer MinION. We applied MinION RNA-Seq for various applications, which would not always be easy using the usual RNA-Seq by Illumina. First, we examined and found that even though the sequencing accuracy was still limited to 92.3%, practically useful RNA-Seq analysis is possible. Particularly, taking advantage of the long-read nature of MinION, we demonstrate the identification of splicing patterns and their combinations as a form of full-length cDNAs without losing precise information concerning their expression levels. Transcripts of fusion genes in cancer cells can also be identified and characterized. Furthermore, the full-length cDNA information can be used for phasing of the SNPs detected by WES on the transcripts, providing essential information to identify allele-specific transcriptional events. We constructed a catalogue of full-length cDNAs in seven major organs for two particular individuals and identified allele-specific transcription and splicing. Finally, we demonstrate that single-cell sequencing is also possible. RNA-Seq on the MinION platform should provide a novel approach that is complementary to the current RNA-Seq.
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Alelos , Perfilação da Expressão Gênica/métodos , Splicing de RNA , Análise de Sequência de RNA/métodos , DNA Complementar , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Tubulocystic carcinoma of the bile duct is extremely rare and has not been reported in the literature. We reported a case of cystic neoplasm of the liver with distinct histopathological features that could not be clearly classified as of either mucinous or intraductal papillary neoplasm. A 68-year-old Japanese patient had a multicystic biliary tumor within the liver. This tumor was detected on follow-up of polymyalgia rheumatica. The exophytic, multicystic, 35 × 50 mm mass was composed of complex tubulocystic structures. We initially suspected cystadenocarcinoma of the liver and performed radical operation. However, pathology ultimately showed it to be very rare tubulocystic carcinoma that derived from the bile duct. We reviewed the literature and describe the process of our differential diagnosis.
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The functional relevancy of mutations occurring in the regulatory regions in cancers remains mostly elusive. Here, we identified and analyzed regulatory mutations having transcriptional consequences in lung adenocarcinoma-derived cell lines. We phased the mutations in the regulatory regions to the downstream heterozygous SNPs in the coding regions and examined whether the ChIP-Seq variant tags of the regulatory SNVs and the RNA-Seq variant tags of their target transcripts showed biased frequency between the mutant and reference alleles. We identified 137 potential regulatory mutations affecting the transcriptional regulation of 146 RefSeq transcripts with at least 84 SNVs that create and/or disrupt potential transcription factor binding sites. For example, in the regulatory region of NFATC1 gene, a novel and active binding site for the ETS transcription factor family was created. Further examination revealed that 31 of these disruptions were presented in clinical lung adenocarcinoma samples and were associated with prognosis of patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Mutação , Fatores de Transcrição NFATC , Proteínas de Neoplasias , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Genômica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismoRESUMO
OBJECTIVE: To investigate the diagnostic utility of endometrial (EM) cell block (CB) cytology for the detection of intrauterine malignancy in postmenopausal women. METHODS: We reviewed the medical records of 104 postmenopausal women between January 2012 and November 2014. We reviewed symptoms upon admission, body mass index, parity, transvaginal ultrasonographic findings, and histopathological results based on CB and conventional cytology. RESULTS: The mean age was 62.6 (range 48-95) years. The mean menopausal age was 50.8 years and the mean duration of menopause was 12.0 years. The sensitivity of CB and conventional cytology was 82.3% (29/35) and 85.7% (30/35) and the specificity was 98.6% (68/69) and 94.2% (65/69), respectively. The sensitivity and specificity of CB cytology combined with conventional cytology were 82.3% (29/35) and 94.2% (65/69), respectively. The predictive values for EM hyperplasia and type-II carcinoma were 100 and 85.7%, respectively. CONCLUSION: CB cytology provides specimens for examination in a single outpatient session. Additionally, immunohistochemical staining can provide useful information for histological diagnosis. A combination of CB and conventional cytology can improve the diagnostic accuracy of EM lesions and may be a valid method for screening in postmenopausal women.
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Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Pós-Menopausa/fisiologia , Idoso , Idoso de 80 Anos ou mais , Citodiagnóstico/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia/métodosRESUMO
Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is an autoimmune form of limbic encephalitis. Eighty percent of patients with anti-NMDA receptor (NMDAR) encephalitis are women, and 39% of those women are reported to have an ovarian teratoma also. When a tumor is also present, prompt surgery can prevent the development of more severe symptoms or the prolongation of symptoms of encephalitis. The current authors encountered two cases in which anti-NMDAR encephalitis was suspected. In these cases, abdominal computed tomography (CT) revealed an ovarian teratoma and both patients underwent a laparoscopic salpingo-oophorectomy. Both patients underwent surgery before a definitive diagnosis was made. Findings in one case did not lead to a diagnosis of anti-NMDAR encephalitis, but symptoms rapidly improved after surgery in both cases. Laparoscopic surgery is minimally invasive, so this approach may be the first step in a treatment algorithm for treatment of a tumor in a patient with anti-NMDAR encephalitis.