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1.
J Mol Diagn ; 26(4): 278-291, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301868

RESUMO

The aim of this study was to evaluate the clinical validity of monitoring urine pellet DNA (upDNA) of bladder cancer (BC) by digital PCR (dPCR) as a biomarker for early recurrence prediction, treatment efficacy evaluation, and no-recurrence corroboration. Tumor panel sequencing was first performed to select patient-unique somatic mutations to monitor both upDNA and circulating tumor DNA (ctDNA) by dPCR. For longitudinal monitoring using upDNA as well as plasma ctDNA, an average of 7.2 (range, 2 to 12) time points per case were performed with the dPCR assay for 32 previously treated and untreated patients with BC. Clinical recurrence based on imaging and urine cytology was compared using upDNA variant allele frequency (VAF) dynamics. A continuous increasing trend of upDNA VAF ≥1% was considered to indicate molecular recurrence. Most (30/32; 93.8%) cases showed at least one traceable somatic mutation. In 5 of 7 cases (71.4%) with clinical recurrence, upDNA VAF >1% was detected 7 to 15 months earlier than the imaging diagnosis. The upDNA VAF remained high after initial treatment for locally recurrent cases. The clinical validity of upDNA monitoring was confirmed with the observation that 26 of 30 cases (86.7%) were traceable. Local recurrences were not indicated by ctDNA alone. The results support the clinical validity of upDNA monitoring in the management of recurrent BC.


Assuntos
DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Humanos , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , DNA Tumoral Circulante/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética
2.
Endocr J ; 71(2): 139-152, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38171883

RESUMO

Nonalcoholic fatty liver disease (NAFLD) develops as a result of unhealthy lifestyle but improves with laparoscopic sleeve gastrectomy (LSG). The transforming growth factor (TGF)-ß signaling pathway reportedly contributes to liver fibrosis, mainly in animal experiments. The aim of the present study was to evaluate changes in serum proteins before and after LSG by proteomic analysis and to investigate their association with NAFLD. This study enrolled 36 severely obese patients who underwent LSG at our hospital from January 2020 to April 2022. As a pilot study, proteomic analysis was conducted on six patients using serum collected before and at 6 months after LSG, and significantly fluctuating proteins were extracted. Subsequently, verification by enzyme-linked immunosorbent assay (ELISA) using collected serum was performed on the remaining 30 patients. The mean weight of enrolled patients was 118.5 kg. Proteomic analysis identified 1,912 proteins, many of which were related to the TGF-ß signaling pathway. Among these proteins, we focused on five TGF-ß-related proteins: asporin, EMILIN-1, platelet factor-4, serglycin, and thrombospondin-1. Verification by ELISA revealed that asporin (p = 0.006) and thrombospondin-1 (p = 0.043) levels significantly fluctuated before and after LSG. Univariate analysis with a linear regression model showed that aspartate aminotransferase (p = 0.045), asporin (p = 0.011), and thrombospondin-1 (p = 0.022) levels were significantly associated with postoperative liver fibrosis. On multivariate analysis, asporin was an independent prognostic factor for postoperative liver fibrosis (95% confidence interval: 0.114-1.291, p = 0.002). TGF-ß-related proteins dramatically fluctuated before and after LSG and were correlated with NAFLD pathogenesis. Asporin may be a useful prognostic marker of liver fibrosis in NAFLD after LSG.


Assuntos
Laparoscopia , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Projetos Piloto , Proteômica , Laparoscopia/efeitos adversos , Cirrose Hepática/cirurgia , Cirrose Hepática/complicações , Gastrectomia , Transdução de Sinais , Trombospondinas , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Resultado do Tratamento
3.
Cancer Sci ; 115(2): 529-539, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38083992

RESUMO

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0-202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence.


Assuntos
Carcinoma de Células de Transição , DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/cirurgia , DNA Tumoral Circulante/genética , Estudos Prospectivos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Biomarcadores , Biomarcadores Tumorais/genética
4.
Cancer Lett ; 581: 216499, 2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-38013050

RESUMO

Most of esophageal squamous cell carcinoma (ESCC) develop in smoking males in Japan, but the genomic etiology and immunological characteristics of rare non-smoking female ECSS remain unclear. To elucidate the genomic and immunological features of ESCC in non-smoking females, we analyzed whole-genome or transcriptome sequencing data from 94 ESCCs, including 20 rare non-smoking female cases. In addition, 31,611 immune cells were extracted from four ESCC tissues and subject to single-cell RNA-seq. We compared their immuno-genomic and microbiome profiles between non-smoking female and smoking ESCCs. Non-smoking females showed much better prognosis. Whole-genome sequencing analysis showed no significant differences in driver genes or copy number alterations depending on smoking status. The mutational signatures specifically observed in non-smoking females ESCC could be attributed to aging. Immune profiling from RNA-seq revealed that ESCC in non-smoking females had high tumor microenvironment signatures and a high abundance of eosinophils with a favorable prognosis. Single-cell RNA-sequencing of intratumor immune cells revealed gender differences of eosinophils and their activation in female cases. ESCCs in non-smoking females have age-related mutational signatures and gender-specific tumor immune environment with eosinophils, which is likely to contribute to their favorable prognosis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Masculino , Feminino , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Prognóstico , Genômica , Microambiente Tumoral
5.
Cancer Med ; 12(5): 6170-6181, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36251535

RESUMO

BACKGROUND: A paradigm shift has occurred in cancer chemotherapy from tumor-specific treatment with cytotoxic agents to personalized medicine with molecular-targeted drugs. Thus, it is essential to identify genomic alterations and molecular features to recommend effective targeted molecular medicines regardless of the tumor site. Nevertheless, it takes considerable expertise to identify treatment targets from primary-sequencing data in order to provide drug recommendations. The Molecular Tumor Board (MTB) denotes a platform that integrates clinical and molecular features for clinical decisions. METHODS: This study retrospectively analyses all the cases of discussion and decision at the MTB in Tohoku University Hospital and summarizes genetic alterations and treatment recommendations. RESULTS: The MTB discussed 1003 comprehensive genomic profiling (CGP) tests conducted in patients with solid cancer, and the resulting rate of assessing treatment recommendations was approximately 19%. Among hundreds of genes in the CGP test, only 30 genetic alterations or biomarkers were used to make treatment recommendations. The leading biomarkers that led to treatment recommendations were tumor mutational burden-high (TMB-H) (n = 32), ERBB2 amplification (n = 24), BRAF V600E (n = 16), and BRCA1/2 alterations (n = 32). Thyroid cancer accounted for most cancer cases for which treatment recommendation was provided (81.3%), followed by non-small cell lung cancer (42.4%) and urologic cancer (31.3%). The number of tests performed for gastrointestinal cancers was high (n = 359); however, the treatment recommendations for the same were below average (13%). CONCLUSION: The results of this study may be used to simplify treatment recommendations from the CGP reports and help select patients for testing, thereby increasing the accuracy of personalized medicine.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Japão , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Biomarcadores Tumorais/genética , Genômica/métodos
6.
Clin Nucl Med ; 47(7): 569-574, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35452002

RESUMO

PURPOSE: The aim of this study was to clarify whether PET with 11C-methyl-l-methionine (11C-met PET) can predict consequential outcomes at the time of discontinuing temozolomide (TMZ)-adjuvant chemotherapy in patients with residual isocitrate dehydrogenase gene (IDH)-mutant lower-grade glioma. PATIENTS AND METHODS: Among 30 patients showing residual lesions of IDH-mutant lower-grade glioma, we compared the tumor-to-normal brain tissue ratio of standardized uptake values (SUVT/N) from 11C-met PET at the time of discontinuing TMZ-adjuvant chemotherapy with putative predictive factors including age, Karnofsky Performance Scale, number of courses of adjuvant therapy, residual tumor size, and promotor methylation status of O6-methylguanine-DNA methyl-transferase gene (MGMT). For each factor, progression-free survival (PFS) was compared between groups divided by cutoff values, determined to predict tumor relapse using receiver operating characteristic curves for each factor. Univariate and multivariate analyses were conducted using log-rank testing and Cox regression analysis, respectively. In addition, PFS was compared between patients grouped by combined findings from multiple predictors identified from univariate and multivariate analyses. RESULTS: Univariate and multivariate analyses identified SUVT/N from 11C-met PET and MGMT methylation status as independent predictors of outcomes after TMZ discontinuation. When comparing 3 groups assigned by the combination of MGMT and SUVT/N findings, PFS differed significantly among groups. CONCLUSIONS: The present study suggested that 11C-met PET at the time of discontinuing TMZ-adjuvant chemotherapy allows prediction of outcomes at least comparable to MGMT methylation status in patients with residual IDH-mutant lower-grade glioma. Further, 11C-met PET allows more precise prediction of outcomes by assessment in combination with MGMT findings.


Assuntos
Neoplasias Encefálicas , Glioma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Radioisótopos de Carbono , Quimioterapia Adjuvante , Metilação de DNA , Progressão da Doença , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Metionina , Recidiva Local de Neoplasia/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Temozolomida/uso terapêutico
7.
J Natl Cancer Inst ; 114(8): 1149-1158, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35437596

RESUMO

BACKGROUND: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome. METHODS: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. RESULTS: Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP-, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction = .049) and PD-L1 (P = .02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P = .0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P = .001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1-r educed" group (86% vs 46%; P = .001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P = .001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. CONCLUSION: This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Antígeno B7-H1/metabolismo , Quimioterapia Adjuvante , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia
8.
Cancer Med ; 11(21): 3960-3968, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35352507

RESUMO

There is no useful biomarker to evaluate treatment response and early relapse in head and neck squamous cell carcinoma (HNSCC). Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual diseases and monitoring treatment effect. We investigated whether individualized ctDNA analysis could help monitor treatment response and relapse in HNSCC. Mutation analysis of tumor and peripheral blood mononuclear cell (PBMC) DNAs of 26 patients with HNSCC was performed using a custom squamous cell carcinoma (SCC) panel. The identified individualized mutated genes were defined as ctDNA candidates. We investigated whether frequent ctDNA monitoring via digital PCR (dPCR) is clinically valid for HNSCC patients. TP53 was the most frequently mutated gene and was detected in 14 of 24 cases (58.2%), wherein two cases were excluded owing to the absence of tumor-specific mutations in the SCC panel. Six cases were excluded because of undesignable and unusable primer-probes for dPCR. Longitudinal ctDNA was monitored in a total of 18 cases. In seven cases, ctDNA tested positive again or did not test negative, and all seven cases relapsed after initial curative treatment. In 11 cases, after initial curative treatment, ctDNA remained negative and patients were alive without recurrence. Patients who remained negative for ctDNA during follow-up after initial curative treatment (n = 11) had a significantly better prognosis than those who reverted to ctDNA positivity (n = 7; p < 0.0001; log-rank test). Individualized ctDNA monitoring using SCC panel and dPCR might be a novel and promising biomarker for HNSCC.


Assuntos
Carcinoma de Células Escamosas , DNA Tumoral Circulante , Neoplasias de Cabeça e Pescoço , Humanos , DNA Tumoral Circulante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Leucócitos Mononucleares , DNA de Neoplasias/genética , Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Mutação , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética
9.
Surg Case Rep ; 7(1): 268, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34928463

RESUMO

BACKGROUND: Metastatic melanoma originating from the choroidal membrane is extremely rare. Here, we report a case of laparoscopic distal pancreatectomy for malignant melanoma that developed after heavy-particle therapy for malignant choroidal melanoma. CASE PRESENTATION: A 43-year-old Japanese woman underwent 70 Gy heavy-particle radiotherapy for a right choroidal malignant melanoma. Positron emission tomography-computed tomography examination was performed 4 years after treatment, when contrast accumulation was observed on the posterior wall of the stomach. Endoscopic ultrasonography and computed tomography showed a mass with contrast enhancement in contact with the stomach wall. Based on the imaging findings, a gastrointestinal stromal tumor of the posterior wall of the lower gastric corpus with extramural growth was suspected. Laparoscopic surgery was performed under general anesthesia. A black-pigmented tumor originating from the pancreas was discovered. Following an intraoperative diagnosis of metastasis of malignant melanoma, a laparoscopic distal pancreatectomy was performed. The pathological diagnosis was pancreatic metastasis of malignant melanoma. The patient was treated with adjuvant immune checkpoint inhibitors and chemotherapy after surgery, which led to long-term survival. CONCLUSIONS: Including this case, only eight case reports on pancreatic resection for metastatic ocular malignant melanoma have been reported. The ocular malignant melanoma with distant metastasis has a poor prognosis. Therefore, in our case, careful follow-up is required. A single pancreatic metastasis from a malignant melanoma of the choroid can be successfully managed by laparoscopic radical resection of the pancreas, and molecularly targeted adjuvant chemotherapy.

10.
Carcinogenesis ; 42(10): 1239-1249, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34559206

RESUMO

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50 or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 versus 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.


Assuntos
Antineoplásicos/uso terapêutico , DNA Tumoral Circulante/sangue , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Resultado do Tratamento
11.
Gastroenterology ; 161(1): 367-368, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33766565
12.
Br J Cancer ; 124(9): 1556-1565, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33658639

RESUMO

BACKGROUND: Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. METHODS: We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. RESULTS: "Founder" mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, "truncal" mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than "non-founder" and "branch" mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. CONCLUSIONS: A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias Colorretais/genética , Cirurgia Colorretal/mortalidade , Mutação , Recidiva Local de Neoplasia/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Seguimentos , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Taxa de Sobrevida , Carga Tumoral
13.
Esophagus ; 18(1): 56-64, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32613327

RESUMO

BACKGROUND: Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. METHODS: We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). RESULTS: The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p < 0.001) and postoperative (EP group vs. control group, 431.5 ± 80 vs. 378 ± 68.7 m, p < 0.001) 6-min walk distance was significantly higher in the EP group than in the control group. The respiratory complications rate was significantly lower in the EP group (4.3%) than in the control group (36%) (p = 0.007). The incidence of atelectasis was particularly significantly lower in the EP group (0%) than in the control group (24%) (p = 0.012). CONCLUSIONS: EP was performed safely for patients before esophagectomy. EP improved the exercise tolerance of the patients before esophagectomy and might be useful in preventing respiratory complications.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Exercício Pré-Operatório , Estudos Retrospectivos
15.
PLoS One ; 15(10): e0239966, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027286

RESUMO

Circulating tumor DNA (ctDNA) is released from tumor cells into blood in advanced cancer patients. Although gene mutations in individual tumors can be diverse and heterogenous, ctDNA has the potential to provide comprehensive biomarker information. Here, we performed multi-region sampling (three sites) per resected specimen from 10 gastric cancer patients followed by targeted sequencing and proteomic profiling using reverse-phase protein arrays. A total of 126 non-synonymous mutations were identified from 30 samples from 10 tumors. Of these, 16 (12.7%) were present in all three regions and were designated as founder mutations. Variant allele frequencies (VAFs) of founder mutations were significantly higher than those of non-founder mutations. Phylogenetic analysis also demonstrated a good concordance between founder and truncal mutations, defined as mutations shared by all simulated clones at the trunk of the tumor phylogenetic tree. These findings led us to prioritize founder mutations for quantitative ctDNA monitoring by digital PCR with individually-designed primer/probe sets. In preoperative plasma, the average ctDNA VAF of founder mutations was significantly higher than that of non-founder mutations (p = 0.039). Proteomic heterogeneity was present across the tumor regions both within and between patients independent of mutational status. Our results suggest that, in practice, mutations having high VAF identified without multi-regional sequencing may be immediately useful for quantitative ctDNA monitoring but do not provide sufficient information to predict the proteomic composition of tumors.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Neoplasias Gástricas , Carga Tumoral , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteômica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
16.
J Hepatobiliary Pancreat Sci ; 27(12): 942-949, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33058554

RESUMO

BACKGROUND: Indications for laparoscopic liver resection (LLR) are continuously expanding. The Japanese Society of Hepato-Biliary-Pancreatic Surgery defines highly difficult hepatectomy as a procedure involving one or more sections (except for left lateral sectionectomy) or anatomical segmentectomy. This study aimed to assess the outcomes of complex LLR procedures and compare their technical difficulties, about which only a little is known to date. METHODS: We performed a retrospective review of the operative outcomes of 118 consecutive patients who underwent pure laparoscopic complex hepatectomy. The surgical outcomes, including operative times, blood loss amounts, and postoperative morbidity rates, were compared among complex LLR procedures. RESULTS: The overall median operative time was 280 minutes, and the median intraoperative blood loss was 86 mL. Two patients required conversion to open laparotomy (1.7%). The postoperative major morbidity rate was 11.0% Posterosuperior segmentectomy, right hemihepatectomy, and anterior sectionectomy required the longest operative times. Anterior and posterior sectionectomy resulted in the highest blood loss, and right hemihepatectomy and anterior sectionectomy resulted in the most complications. CONCLUSIONS: The surgical difficulties associated with complex LLR procedures vary. It is critical to recognize the specific risks and cautionary points to ensure patient safety and provide proper systemic training to surgeons.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
17.
Int J Surg Case Rep ; 75: 152-156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32950945

RESUMO

INTRODUCTION: Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. Here, we report a case of retroperitoneal recurrence of PMME successfully treated with the anti-programmed cell death 1 antibody, nivolumab. PRESENTATION OF CASE: A 70-year-old male with dysphagia was referred to our hospital. Esophagogastroscopy showed an elevated tumor in the lower thoracic esophagus. A histopathological examination of the biopsy revealed poorly differentiated squamous cell carcinoma. The patient was diagnosed with clinical T3N1M0 stage III esophageal squamous cell carcinoma and was treated with neoadjuvant chemotherapy followed by radical esophagectomy. A postoperative histopathological examination revealed that atypical cells with a brown pigment were scattered in the tumor. Immunohistochemical staining demonstrated positive expression of human melanoma black 45, melan A, and S100. A pathological diagnosis of PMME was confirmed. Sixteen months after surgery, abdominal computed tomography revealed solitary retroperitoneal recurrence in the lateral portion of the ascending colon. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) showed hypermetabolic accumulation with a maximum standardized uptake value of 5.8. The patient was treated with nivolumab (240 mg) every two weeks. After eight courses of nivolumab, abnormal accumulation of the retroperitoneal mass disappeared on PET, and this therapeutic effect continued for 20 months. CONCLUSIONS: Nivolumab was effective for recurrence of PMME in our case. There are few reports of treatment with nivolumab for PMME. Further studies are necessary to establish the usefulness of nivolumab for PMME in the future.

18.
Int J Surg Case Rep ; 74: 27-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32777763

RESUMO

INTRODUCTION: Most esophageal carcinosarcoma (ECS) tumors present as a polypoid tumor that is continuous with the superficial lesion and suspended by a pedicle. Here, we report a case of ECS in which a polypoid lesion sloughed off before surgery. PRESENTATION OF CASE: A 76-year-old man with dysphagia was admitted to our hospital. Esophagogastroscopy revealed a 20-mm polypoid tumor continuous with a superficial lesion and attached to the lesion by a thin pedicle in the mid-thoracic esophagus. Histopathological examination of the endoscopic biopsy showed that the superficial lesion was a moderately differentiated squamous cell carcinoma and that the polypoid tumor contained a sarcomatous element. He was diagnosed with ECS and underwent radical esophagectomy with three-field lymph node dissection. In the resected specimen, no polypoid tumor was found, and only a superficial lesion was observed. The histopathological findings revealed only squamous cell carcinoma, and the pathological diagnosis was esophageal squamous cell carcinoma, pT1bN0M0, pathological stage I. The patient was discharged from the hospital 22 days after surgery and did not experience any complications. He is currently alive and remained cancer-free for three years since surgery was performed. DISCUSSION: Due to the distinctive configuration in which the polypoid lesion was connected to the superficial cancerous lesion by a very thin pedicle, researchers suggested that the polypoid tumor, which consisted of a sarcomatous element, was sloughed off before surgery. CONCLUSION: We encountered a rare case of ECS in which the sarcomatous element sloughed off prior to surgical resection.

19.
World J Surg Oncol ; 18(1): 170, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677964

RESUMO

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving surgery for the treatment of early gastric cancer in East Asian countries. Therefore, this study aimed to evaluate the feasibility and safety of totally laparoscopic PPG (TLPPG) with intracorporeal anastomosis. METHODS: A total of 43 patients with early gastric cancer underwent laparoscopy-assisted PPG (LAPPG) with extracorporeal anastomosis between May 2006 and November 2012. The operative outcomes of 22 patients who underwent TLPPG between November 2012 and February 2019 were evaluated, and data were compared with that of the LAPPG group. RESULTS: No significant difference in the operative time was observed between the two groups. Blood loss was lower in the TLPPG group (18.5 mL) than in the LAPPG group (30.7 mL, p = 0.008), and the length of abdominal incision was shorter in the TLPPG group (3.8 cm) than in the LAPPG group (4.7 cm, p < 0.001). No significant difference in the complication rate was observed between the two groups (13.6% in the TLPPG vs. 9.3% in the LAPPG group, p = 0.594). No anastomosis-related complications occurred in either group. No significant between-group difference was observed in the delayed gastric emptying (TLPPG, 9.1 vs. LAPPG, 7%, p = 0.762). The initiation of postoperative fluid (TLPPG, 1.0 day vs. LAPPG, 3.0 days, p < 0.001) and meal (TLPPG, 3.0 days vs. LAPPG, 4.0 days, p < 0.001) intake was earlier in the TLPPG group than in the LAPPG group. No significant between-group difference was observed in the postoperative hospital stay. CONCLUSIONS: The findings of this study suggest that TLPPG with intracorporeal reconstruction not only is as feasible and safe as LAPPG for the treatment of patients with early gastric cancer but also provides certain advantages such as reduced blood loss and wound size.


Assuntos
Laparoscopia , Neoplasias Gástricas , Estudos de Viabilidade , Gastrectomia , Gastrostomia , Humanos , Prognóstico , Piloro/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
20.
Int J Surg Case Rep ; 72: 166-171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32535535

RESUMO

INTRODUCTION: Pulmonary metastases from esophageal squamous cell carcinoma (ESCC) are often detected bilateral and multiple lesions and are often accompanied by metastases to other sites. The concept of oligometastasis has been developed, and limited distant metastases have been considered as indications for surgical resection for the purpose of extending overall survival. We herein present a long-surviving case of super-late pulmonary recurrence of ESCC, seven years after radical esophagectomy. PRESENTATION OF CASE: A 71-year-old woman who underwent radical subtotal esophagectomy with three-field lymph node dissection with a diagnosis of an advanced poorly differentiated ESCC with cT3N1M0 seven years ago visited our hospital. Chest X-ray and computed tomography at the 7-year follow-up revealed a solitary pulmonary tumor, 1.5 cm in diameter, at the right middle lobe without any extrapulmonary metastases; however, we could not diagnose whether primary lung cancer or pulmonary metastasis of ESCC was present. Therefore, we performed thoracoscopic partial resection of the right middle lobe. A histopathological examination including immunohistochemical staining revealed that the tumor was not derived from both alveolar epithelium and neuroendocrine cells and was diagnosed as pulmonary oligometastasis of ESCC. She has been followed for four years without re-recurrence. CONCLUSION: Pulmonary oligometastases of ESCC should be considered as surgical indications if the tumor is detected after a long disease-free interval without any extrapulmonary recurrences.

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