RESUMO
Advanced gastric and gastroesophageal junction cancers (GC/GEJCs) harbor diverse molecular signatures, highlighting the need for intricate evaluations to identify potential therapeutic targets. Although whole-transcriptome sequencing (WTS) has emerged as a useful tool for understanding these molecular intricacies, its clinical implications have yet to be fully elucidated. This study evaluated the correlation between immunohistochemistry (IHC) and WTS, compared their clinical significance, and identified potential therapeutic targets undetectable through IHC alone. We enrolled 140 patients with advanced GC/GEJC and assessed them using IHC for six pivotal biomarkers: claudin-18 (CLDN18), human epidermal growth factor receptor 2 (HER2), multiple receptor tyrosine kinases (RTKs), and programmed death ligand 1 (PD-L1). Concurrently, WTS was employed as part of the analyses in MONSTAR-SCREEN-2, a multicenter multiomics study. IHC analysis revealed 16.4% HER2, 39.3% CLDN18 (2+/3 + ≥75%), and 15.8% PD-L1 (combined positive score ≥ 10) positivity, among other molecular markers. Significant correlations were observed between IHC and WTS for all six pivotal biomarkers. Among nineteen HER2 IHC-positive patients treated with anti-HER2 therapeutics, ERBB2 status in WTS was significantly associated with progression-free survival (ERBB2-high vs. -low: median 9.0 vs. 5.6 months, log-rank p = 0.046). IHC-based molecular profiling revealed significantly high expression of CLDN18 in RTK-negative patients, with 78.4% positive for either CLDN18 or PD-L1. Additionally, WTS revealed elevated expression of pivotal biomarkers in patients displaying negative targetable biomarkers via IHC. Our findings highlighted the significant correlation between IHC and WTS, reinforcing the clinical utility of WTS. A subset with IHC-negative but WTS-positive status may benefit from specific biomarker-targeted therapies.
Assuntos
Biomarcadores Tumorais , Neoplasias Esofágicas , Junção Esofagogástrica , Imuno-Histoquímica , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Masculino , Feminino , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Idoso , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Junção Esofagogástrica/patologia , Junção Esofagogástrica/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Claudinas/genética , Claudinas/metabolismo , Adulto , Idoso de 80 Anos ou mais , Transcriptoma , Perfilação da Expressão Gênica/métodosRESUMO
OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.
Assuntos
Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Prognóstico , Recidiva Local de Neoplasia/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Colorretais/patologia , Reto , Estudos RetrospectivosRESUMO
BACKGROUND: Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP). METHODS: This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP. DISCUSSION: If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy. TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ].
Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Japão/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Recidiva Local de Neoplasia/cirurgia , Resultado do Tratamento , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
Circulating tumor DNA (ctDNA) is the fraction of cell-free DNA in patient blood that originates from a tumor. Advances in DNA sequencing technologies and our understanding of the molecular biology of tumors have increased interest in exploiting ctDNA to facilitate detection of molecular residual disease (MRD). Analysis of ctDNA as a promising MRD biomarker of solid malignancies has a central role in precision medicine initiatives exemplified by our CIRCULATE-Japan project involving patients with resectable colorectal cancer. Notably, the project underscores the prognostic significance of the ctDNA status at 4 weeks post-surgery and its correlation to adjuvant therapy efficacy at interim analysis. This substantiates the hypothesis that MRD is a critical prognostic indicator of relapse in patients with colorectal cancer. Despite remarkable advancements, challenges endure, primarily attributable to the exceedingly low ctDNA concentration in peripheral blood, particularly in scenarios involving low tumor shedding and the intrinsic error rates of current sequencing technologies. These complications necessitate more sensitive and sophisticated assays to verify the clinical utility of MRD across all solid tumors. Whole genome sequencing (WGS)-based tumor-informed MRD assays have recently demonstrated the ability to detect ctDNA in the parts-per-million range. This review delineates the current landscape of MRD assays, highlighting WGS-based approaches as the forefront technique in ctDNA analysis. Additionally, it introduces our upcoming endeavor, WGS-based pan-cancer MRD detection via ctDNA, in our forthcoming project, SCRUM-Japan MONSTAR-SCREEN-3.
Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Neoplasia Residual , Sequenciamento Completo do Genoma , Humanos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Sequenciamento Completo do Genoma/métodos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Japão , Neoplasias Colorretais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Prognóstico , Medicina de Precisão/métodos , Neoplasias/genética , Neoplasias/sangue , Neoplasias/diagnósticoRESUMO
The prognosis of locally advanced colon cancer (LACC) with surgical resection followed only by adjuvant chemotherapy is poor. Preoperative chemotherapy for LACC patients with risk factors such as cT4bN+ or cT3-4aN2-3 has attracted attention. Here, the authors describe the rationale and design of JCOG2006, a randomized phase II study comparing preoperative chemotherapy with mFOLFOX6 versus FOLFOXIRI for LACC. Their efficacy and safety are evaluated and a determination of which is the more promising treatment will be conducted in a subsequent phase III trial. A total of 86 patients will be accrued from 44 institutions over 2 years. The primary end point is the proportion of patients with a Tumor Regression Score of 0-2, and secondary end points include overall survival, response rate and adverse events. Clinical Trial Registration: jRCTs031210365 (https://jrct.niph.go.jp/).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Terapia Neoadjuvante , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Macroscopic type 4 and large type 3 gastric cancer, mostly overlapping with scirrhous or linitis plastica type, exhibit a highly invasive nature and show unfavorable prognosis after curative surgery, even with adjuvant chemotherapy. A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin for this population. The current authors initiated a randomized phase II study comparing neoadjuvant chemotherapy with 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for type 4 and large type 3 gastric cancer. 76 patients are planned to be enrolled over two years. The primary end point is the proportion of patients with a pathological response (grade 1b or higher) and secondary end points include overall survival and adverse events. Clinical Trial Registration: jRCTs031230231 (rctportal.niph.go.jp).
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Docetaxel/uso terapêutico , Oxaliplatina/efeitos adversos , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
Chemotherapy plus antiangiogenic agents, including bevacizumab, ramucirumab and aflibercept, is a standard second-line treatment for patients with metastatic colorectal cancer, but which specific agents should be selected is ambiguous due to a lack of clear evidence from prospective studies. Previous reports have suggested ramucirumab and aflibercept could be more effective than bevacizumab in patients with high VEGF-D and high VEGF-A, respectively. JCOG2004 is a three-arm, randomized, phase II study to identify predictive biomarkers for these agents in patients who have failed first-line treatment. The study will enroll 345 patients from 52 institutions for 2 years, with progression-free survival in high VEGF-D (bevacizumab vs ramucirumab) and high VEGF-A (bevacizumab vs aflibercept) serving as the primary end point. Clinical Trial Registration: jRCTs031220058 (www.jrct.niph.go.jp).
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Bevacizumab/efeitos adversos , Neoplasias Colorretais/patologia , Fator D de Crescimento do Endotélio Vascular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Oxaliplatina , Camptotecina/uso terapêutico , Estudos Prospectivos , Fluoruracila/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Biomarcadores , Leucovorina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase II como AssuntoRESUMO
INTRODUCTION: Splenectomy for proximal gastric cancer was found to offer no survival benefit in a randomized trial clarifying the role of splenectomy (JCOG0110 study). Although many studies have explored risk factors for morbidities following total gastrectomy, none have assessed the risk factors for postoperative complications in spleen-preserving total gastrectomy. METHODS: Using data from 505 patients enrolled in a previous randomized trial, risk factors for postoperative complications were identified by multivariable logistic regression analysis. Then, the risk factors were assessed separately between splenectomy and spleen-preserving total gastrectomy. RESULTS: Postoperative complications were identified in 119 patients (23.6%) and were more common following splenectomy than following spleen-preserving surgery (30.7% and 16.1%, respectively, p < 0.01). Multivariable analysis revealed that age ≥65 years (p = 0.032), body mass index ≥25 (p = 0.003), and blood loss ≥350 (p = 0.019) were independent risk factors for postoperative complications in the entire cohort. Among them, only body mass index was a significant independent risk factor for complications in both spleen preservation (p = 0.047) and splenectomy groups (p = 0.017). CONCLUSION: Risk factors for postoperative complications were essentially the same between splenectomy and spleen preservation. Being overweight increased the risk of postoperative complications.
Assuntos
Esplenectomia , Neoplasias Gástricas , Humanos , Idoso , Esplenectomia/efeitos adversos , Baço/cirurgia , Neoplasias Gástricas/cirurgia , Gastrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Excisão de Linfonodo , Fatores de Risco , Estudos RetrospectivosRESUMO
The standard treatment for pathological N2 Stage III non-small cell lung cancer with negative surgical margins in Japan is cisplatin-based adjuvant chemotherapy. However, recent studies suggest that the addition of thoracic radiotherapy after adjuvant chemotherapy prolongs survival. While thoracic radiotherapy is considered to prolong survival by improving locoregional control, it is known to increase radiation-induced adverse events. We began a randomized controlled trial in January 2021 in Japan to confirm the superiority of radiotherapy over observation after adjuvant chemotherapy in pathological N2 Stage III non-small cell lung cancer patients with negative surgical margins. We aim to accrue 330 patients from 47 institutions over 5 years. The primary endpoint is relapse-free survival; the secondary endpoints are overall survival, proportion of patients completing radiotherapy in the radiotherapy arm, early adverse events, late adverse events in the radiotherapy arm, serious adverse events and local recurrence.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimioterapia Adjuvante/métodos , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Japão , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: To investigate the residual pattern of esophageal cancer in the esophageal wall after neoadjuvant chemotherapy (NAC) and its clinical significance. BACKGROUND: NAC is a standard treatment for locally advanced esophageal cancer; however, residual tumor patterns in resected specimens after NAC and their clinico-pathological characteristics remain unknown. METHODS: One hundred twenty consecutive patients with cT3 or deeper esophageal cancer underwent curative esophagectomy after NAC and achieved grade 2 histological responses between 2000 and 2016. Hematoxylin-eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations between these Types and clinico-pathological factors, including prognosis. RESULTS: Forty-five (38%) specimens had no residual tumor cells in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3, and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9 (8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4 more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the 4 Types. CONCLUSIONS: After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but approximately 40% of specimens showed no tumor cells in the mucosal layer. Deep and diffuse remnant patterns were associated with high risks of pleural dissemination and distant metastasis.
Assuntos
Quimioterapia Adjuvante , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Terapia Neoadjuvante , Neoplasia Residual/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
PURPOSE: Preoperative chemotherapy is an effective treatment option for resectable gastric cancer, but it is associated with various adverse events (AEs). This study aimed to identify the body composition parameters that most accurately predicted the incidence of AEs in preoperative chemotherapy for gastric cancer. METHODS: The present study included a total of 114 patients who received preoperative chemotherapy for resectable gastric cancer. We estimated various body composition parameters using computed tomography images obtained before preoperative chemotherapy. Their associations with the incidence of hematological (grade ≥ 3) and non-hematological (grade ≥ 2) AEs were analyzed by multivariate logistic regression analyses. RESULTS: Seventy-two of the 114 (63.2%) patients experienced hematological AEs (grade ≥ 3), specifically neutropenia in 68 (59.6%), anemia in 5 (4.9%), and thrombocytopenia in 3 (2.6%). Meanwhile, 59 patients (51.8%) experienced non-hematological AEs (grade ≥ 2), namely hypoalbuminemia in 31 (27.2%), anorexia in 24 (21.1%), and febrile neutropenia in 17 (14.9%). Multivariate analyses revealed that a low psoas muscle index (PMI) was an independent risk factor for the incidence of both hematological and non-hematological AEs. CONCLUSIONS: Patients with a low PMI experienced an increased incidence of hematological and non-hematological toxicities during preoperative chemotherapy for gastric cancer. Clinicians should be aware of these risks in this population.
Assuntos
Antineoplásicos/efeitos adversos , Composição Corporal , Cuidados Pré-Operatórios , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Anemia/induzido quimicamente , Anemia/epidemiologia , Anorexia/induzido quimicamente , Anorexia/epidemiologia , Antineoplásicos/toxicidade , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/epidemiologia , Humanos , Hipoalbuminemia/induzido quimicamente , Hipoalbuminemia/epidemiologia , Músculos Psoas/patologia , Fatores de Risco , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologiaRESUMO
BACKGROUND: Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are candidate predictors for the response to immune checkpoint inhibitors, and may predict chemotherapy sensitivity. We investigated the simultaneous expression of mutL homolog 1 (MLH1), a mismatch repair gene, and PD-L1 in gastric cancers. METHODS: We examined MLH1 and PD-L1 expression in surgical specimens from 285 gastric cancer patients treated with or without preoperative chemotherapy, and assessed the relation between expression results and both histological response and recurrence-free survival (RFS). RESULTS: Of 285 patients, 28 (9.8%) and 70 (24.6%) exhibited negative MLH1 and high PD-L1 expression, respectively. Most MLH1-negative tumors (85.7%) showed high MSI, and these tumors exhibited high PD-L1 expression more frequently than MLH1-positive tumors (57.1% vs. 21.0%, P < 0.001). MLH1-negative patients were significantly less likely to respond to preoperative chemotherapy than MLH1-positive patients (16.7% vs. 61.2%, P = 0.005), whereas there was no significant difference between high- and low-PD-L1 expression patients (55.9% vs. 56.6%, P = 0.95). RFS in patients without preoperative chemotherapy was significantly longer in the MLH1-negative group than in the MLH1-positive group (HR 0.30; 95% CI 0.09-0.95; P = 0.030), whereas in patients with preoperative chemotherapy there was no significant difference in RFS between the two groups (HR 0.70; 95% CI 0.30-1.63; P = 0.41). PD-L1 expression was not associated with RFS in patients with or without chemotherapy. CONCLUSIONS: Loss of MLH1 was associated with chemoresistance and did not prolong survival following neoadjuvant chemotherapy. The strong association between MLH1 and MSI status suggests that immune checkpoint inhibitors may be preferable to conventional chemotherapy for MLH1-negative gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Recidiva Local de Neoplasia/patologia , Cuidados Pré-Operatórios , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Taxa de SobrevidaRESUMO
BACKGROUND: Elderly patients with gastric cancer are frequently treated surgically in current clinical practice. Although several studies have investigated short-term outcomes after gastrectomy in elderly patients, most did not evaluate long-term outcomes. METHODS: We analyzed 1154 consecutive patients who underwent curative gastrectomy for gastric cancer between 2001 and 2013. We classified them into two groups: the elderly group (n = 241), consisting of patients aged ≥75 years, and the non-elderly group (n = 913), consisting of patients aged <75 years, and compared the short- and long-term outcomes between the two groups. The risk factors for death from other diseases in elderly patients were also examined. RESULTS: Although the incidence of postoperative pneumonia was significantly higher in the elderly group (P < 0.001), the proportion of overall postoperative complications did not differ significantly between the two groups (P = 0.097). The disease-specific survival was similar between the two groups (P = 0.743), whereas the overall survival in the elderly group was significantly shorter than that in the non-elderly group (P < 0.001) because of a higher incidence of death from other diseases throughout all gastric cancer stages. Multivariate analysis revealed that a low preoperative prognostic nutrition index (PNI) and multiple comorbidities were significant risk factors for death from other diseases within 5 years in the elderly group. CONCLUSIONS: Despite acceptable short-term outcomes, long-term outcomes in elderly patients with gastric cancer were poor due to the high incidence of death from other diseases. Indications for surgery in elderly patients with a low PNI or multiple comorbidities should be considered carefully.
Assuntos
Pneumonia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Gastrectomia/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de TempoRESUMO
INTRODUCTION: We aimed to analyze the clinical and histological effects of chemotherapy in superficial esophageal squamous cell carcinoma (SESCC). METHODS: We analyzed tumor samples from five patients with cT1bN1M0 who underwent subtotal esophagectomy following two courses of a new triplet chemotherapy regimen including docetaxel, cisplatin, and 5-fluorouracil (DCF). To assess the histological effects of chemotherapy, resected specimens were analyzed by macroscopic examination, hematoxylin & eosin (HE) staining, immunohistochemical (IHC) staining (p53, Ki-67 and cytokeratin) and periodic acid-Schiff (PAS) staining. RESULTS: All five patients had a pathological T stage of T0/1a-LPM/1a-MM/1b (1/2/1/1) and histological grade of grade1a/1b/2/3 (1/1/2/1). Endoscopic examination revealed substantial shrinkage of lugol-voiding lesions (LVLs) in all cases. One case showed complete LVL disappearance, and resected specimen examination confirmed pathological complete response (pCR). IHC and PAS staining revealed that most initial LVLs were PAS-negative. Obvious viable cells were confirmed in two cases. The other three cases exhibited nuclear atypia and strong expression of p53 and Ki-67 in the basal layer of mucosa or lamina propria mucosae, even though the superficial layer of mucosa showed no obvious LVLs with PAS-positive. p53-positive lesions were also observed in Ki-67-positive. This indicated discordance between the endoscopic findings and histopathological evaluation. CONCLUSION: DCF chemotherapy alone had a substantial therapeutic effect on SESCC in all cases. However, despite the normal appearance of the mucosal surface, viable cancer cells remained below the basal layer of mucosa. Careful attention should be paid when diagnosing clinical CR, or securing a resection margin of SESCC after DCF chemotherapy.
RESUMO
The number of patients with end-stage heart failure treated by a left ventricular assist device (LVAD) is dramatically increasing, because the LVAD has been widely accepted for its clinical results. According to the initiation of destination therapy, the prevalence of malignancy in patients with an LVAD is estimated to increase. In patients with LVADs, abdominal surgery for visceral malignancy is associated with technical difficulties because of the presence of an LVAD pump or the driveline which is located transversely in the preperitoneal space. Herein, we describe the technical management for complete resection of gastric cancer in a patient with an LVAD.
Assuntos
Carcinoma de Células em Anel de Sinete/cirurgia , Gastrectomia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Neoplasias Gástricas/cirurgia , Carcinoma de Células em Anel de Sinete/complicações , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/complicaçõesRESUMO
A 71-year-old man was admitted to our hospital for epigastric pain. Upper gastrointestinal endoscopy revealed a type 2- like ulcerative lesion in the posterior wall of the upper and middle part of the stomach. Endoscopic biopsies showed malignant T-cell lymphoma histologically. A chest CT scan revealed a nodule in the apex of right lung, suggestive of primary lung cancer. A total gastrectomy with D2 lymphadenectomy and distal pancreatectomy with splenectomy was performed. Seventy-three days after surgery, the patient developed a lung abscess in the middle lobe of the right lung. A wedge-shaped resection of the upper lobe and total resection of the middle lobe of the right lung was performed. Histological examination revealed a primary pulmonary mucosa-associated lymphoid tissue lymphoma in the upper lobe of right lung and an abscess caused by Pseudomonas aeruginosa in the middle lobe of the right lung. Twelve months after surgery the man died of suffocation because of aspiration due to esophageal stenosis caused by progression of metastasis of the paraesophageal lymph node.
Assuntos
Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Gastrectomia , Humanos , Neoplasias Pulmonares/cirurgia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Linfoma não Hodgkin/cirurgia , Masculino , Neoplasias Primárias Múltiplas/cirurgia , Pancreatectomia , Neoplasias Gástricas/cirurgiaRESUMO
A 68-year-old man diagnosed with type 0-â gastric cancer by gastrointestinal endoscopy underwent urgent distal gastrectomy due to a perforation during endoscopic submucosal resection. Pathological examination revealed pT3N2M0, pStage â ¢A. TS-1 was administered as adjuvant chemotherapy. Laboratory examinations 10 months after surgery revealed leukocytosis (19,100/mL). Positron emission tomography-CT demonstrated metastases in the bone marrow and ascending colon as well as around the liver. Chemotherapy using nab-PTX had poor efficacy and the leukocytosis worsened. Serum granulocyte- colony stimulating facto (r G-CSF) was high at 1,640 pg/mL, and immunohistochemical staining was positive for G-CSF. Thus, the patient was diagnosed with G-CSF-producing gastric cancer. The tumor was also positive for HER2 antibody by immunohistochemical staining. Combination therapy using TS-1 plus CDDP plus trastuzumab resulted in a good response, and the leukocytosis and elevated serum G-CSF gradually improved. The patient is living 30 months postoperatively and remains on chemotherapy.
Assuntos
Fator Estimulador de Colônias de Granulócitos/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/uso terapêutico , Idoso , Gastrectomia , Humanos , Masculino , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
An 81-year-old woman was admitted for leg edema. She was found to have membranous glomerulonephritis with advanced gastric cancer after renal biopsy and endoscopic examination. Serum albumin was 1.4 g/dL and total protein was 4 g/dL on admission. After albumin was administered, distal gastrectomy was performed. Albumin administration continued post-operatively. The post-operative course was unremarkable and she was discharged on post-operative day 19. Six months after the operation, serum albumin gradually increased and uric protein volume decreased. Possible remission of membranous glomerulonephritis with gastric cancer can be expected after gastrectomy but careful perioperative management is required.
Assuntos
Adenocarcinoma/complicações , Glomerulonefrite Membranosa/etiologia , Neoplasias Gástricas/complicações , Adenocarcinoma/cirurgia , Idoso de 80 Anos ou mais , Biópsia , Feminino , Gastrectomia , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
The Guidelines for Colorectal Cancer Treatment list indication and curative resection criteria for the endoscopic resection of mucosal and submucosal invasive colorectal cancers. Here, we report the case of a woman who underwent endoscopic mucosal resection (EMR) but should have undergone curative resection because the submucosal invasion depth in this case was 1,200 mm; however, she did not undergo additional curative surgery. Although liver and lymph node metastases were observed 7 years later, we were able to resect all of these tumors after neoadjuvant chemotherapy. We strongly recommend additional curative surgery for patients who fulfill the criteria for curative resection after EMR because of the very high recurrence rates in such cases.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias do Colo Sigmoide/patologia , Idoso de 80 Anos ou mais , Colonoscopia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Recidiva , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
The patient was an 86-year-old woman. She underwent right breast-conserving surgery and sentinel lymph node biopsy for breast cancer in August 2006. The pathological diagnosis was invasive ductal carcinoma, T1N0M0, Stage â , ER (+), PgR (-), HER2 (-). She was treated with tamoxifen for 5 years as adjuvant therapy and showed no signs of recurrence. In November 2014, CA15-3 was elevated and an accumulation of FDG in the right paracolic sulcus was observed on PET-CT. Peritoneal metastasis of breast cancer was suspected, and an operation was performed for a definitive diagnosis. During the operation, the tumor was seen on the paracolic sulcus, and laparoscopic-assisted right hemicolectomy was performed. A poorly differentiated adenocarcinoma was diagnosed by pathological examination, and immunostaining results were as follows: CK7(+), CK20(-), mammaglobin (-), GCDFP-15 (-), ER (-), PgR (-), and HER2 (-). Because there was no original lesion other than the breast cancer, the tumor was diagnosed as a metastasis of breast cancer. The frequency of peritoneal metastasis of breast cancer is low. In this case, pathological diagnosis was necessary for a definitive diagnosis. A change of subtype was also confirmed, and the treatment strategy was decided appropriately. Surgical resection should be considered for peritoneal metastasis of breast cancer when the operation can be performed safely.