RESUMO
PURPOSE: In Japan, the number of distal gastrectomy for patients ≥ 80 years old is increasing, whereas that of total gastrectomy is decreasing. Surgeons seem to avoid total gastrectomy for elderly patients. Total gastrectomy is reported to have a poorer prognosis than distal gastrectomy, and postoperative pneumonia may be involved in the cause. METHODS: The medical records of 39 and 108 patients ≥ 80 years old who underwent total and distal gastrectomy, respectively, at 2 affiliated institutions between 2010 and 2019 were retrospectively reviewed. Prognoses were compared between the two groups, focusing on death from pneumonia. RESULTS: The median overall survival time after total and distal gastrectomy was 21.3 and 74.1 months, respectively, with a significantly poorer prognosis after total gastrectomy than after distal gastrectomy (p < 0.01, hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.37-3.53). The gastric cancer-specific survival time was significantly worse after total gastrectomy than after distal gastrectomy (p < 0.01, HR 2.73, 95% CI 1.29-5.79). The pneumonia-specific survival time was also significantly worse after total gastrectomy than after distal gastrectomy (p = 0.01, HR 3.44, 95% CI 1.25-9.48). CONCLUSIONS: Patients who underwent total gastrectomy had a poorer prognosis than those who underwent distal gastrectomy, because many patients died of pneumonia early after total gastrectomy.
Assuntos
Pneumonia , Neoplasias Gástricas , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Prognóstico , Gastrectomia/efeitos adversos , Pneumonia/epidemiologia , Pneumonia/etiologiaRESUMO
Appendiceal goblet cell adenocarcinoma(AGCA)is a newly designated pathological term adopted in the 5th edition of the WHO classification. It is synonymous with goblet cell carcinoid, which was previously categorized as a part of appendiceal carcinoid. However, since 2018, it has been classified as a subtype of adenocarcinoma. We have experienced 3 cases of this relatively rare tumor, of which 2 were initially diagnosed with acute appendicitis and were diagnosed with AGCA by pathological examination after an emergency appendectomy. Each of them underwent additional ileocolic resection with lymph node dissection as the second surgery. In the 3rd case, an appendiceal tumor was detected during preoperative examinations for an ovarian tumor. Staging laparoscopy revealed comorbid peritoneal dissemination, and only the appendix and right ovary were removed in the consecutive surgery. The ovarian tumor was pathologically diagnosed as a metastasis of AGCA. In this case, the introduction of oxaliplatin-based systemic chemotherapy after surgery achieved a complete response after more than 2 years. Although no recurrence has been observed in all 3 cases to date, AGCA is considered highly malignant compared to conventional appendiceal carcinoids. Therefore, it is crucial to practice multidisciplinary treatments, including sufficient radical surgery based on a precise diagnosis of AGCA, as is performed for advanced colorectal cancer.
Assuntos
Adenocarcinoma , Neoplasias do Apêndice , Tumor Carcinoide , Neoplasias Ovarianas , Feminino , Humanos , Células Caliciformes , Tumor Carcinoide/cirurgia , Adenocarcinoma/cirurgia , Neoplasias do Apêndice/cirurgiaRESUMO
This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.
Assuntos
Neoplasias Esofágicas , Terapia com Prótons , Humanos , Prótons , Estudos Prospectivos , Neoplasias Esofágicas/terapia , Terapia com Prótons/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodosRESUMO
BACKGROUND: To date, no in-depth studies have focused on the impact of various clinical characteristics of esophageal squamous cell carcinoma (ESCC), including its association with subjective symptoms, on patient prognosis. We aimed to investigate the clinical factors that affect the prognosis of patients with ESCC and to clarify how subjective symptoms are related to prognosis. METHODS: We retrospectively evaluated the clinical records of 503 consecutive patients with ESCC from April 2011 to December 2019. Six established prognostic factors for ESCC (body mass index, alcohol drinking, cigarette smoking, sex, clinical stage, and age) and subjective symptoms were used to subgroup patients and analyze survival differences. Next, the patients were divided into two groups: a symptomatic group and an asymptomatic group. In the symptomatic group, differences in the incidence of subjective symptoms according to tumor size, tumor location, macroscopic tumor type, and clinical stage were examined. Finally, subjective symptoms were divided into swallowing-related symptoms and other symptoms, and their prognosis was compared. RESULTS: Multivariate Cox regression analysis identified sex [hazard ratio (HR) 1.778; 95% CI 1.004-3.149; p = 0.049], TNM classification (HR 6.591; 95% CI 3.438-12.63; p < 0.001), and subjective symptoms (HR 1.986; 95% CI 1.037-3.803; p = 0.0386) as independent risk factors for overall survival. In the symptomatic group, the mean time from symptom onset to diagnosis was 2.4 ± 4.3 months. The incidence of subjective symptoms differed by clinical stage, and the prognosis of patients with swallowing-related symptoms was significantly worse than that of patients with other symptoms. CONCLUSION: The results of this study suggest that screening by upper gastrointestinal endoscopy, independent of subjective symptoms (especially swallowing-related symptoms), may play an important role in the early detection and improvement of prognosis of ESCC, although further validation in a large prospective study is needed.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. METHODS: The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. RESULTS: In univariate analyses, age (≥ 90 vs. ≥ 80, < 85), performance status (3 vs. 0), American Society of Anesthesiologists physical status (ASA-PS) (3, 4 vs. 1, 2), Onodera's prognostic nutritional index (< 40 vs. ≥ 45), the physiological score of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) (≥ 40 vs. ≥ 20, ≤ 29), surgical approach (laparoscopic vs. open), extent of gastrectomy (total, proximal vs. distal), extent of lymphadenectomy (D1 vs. ≥ D2), pathological stage (II-IV vs. I), and residual tumor (R1 vs. R0) were significantly correlated with worse overall survival. Multivariate analysis revealed that ASA-PS [3, 4 vs. 1, 2, hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.24-4.24], extent of gastrectomy (total vs. distal, HR 2.17, 95% CI 1.10-4.31) (proximal vs. distal, HR 4.05, 95% CI 1.45-11.3), extent of lymphadenectomy (D0 vs. ≥ D2, HR 12.4, 95% CI 1.58-97.7), and pathological stage were independent risk factors for mortality. CONCLUSIONS: ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.
Assuntos
Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Excisão de Linfonodo , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
This is a report on a case of CA19-9-producing cancer of esophagogastric junction with rectal cancer and a suspicion of Krukenberg tumor, a metastasized ovarian tumor that would mean an inoperable condition of cancer progression if that were true. This was a case of a woman in her 60s who was diagnosed with double cancers at the esophagogastric junction and rectum with a swollen left ovary. She had a laparoscopic bilateral salpingo-oophorectomy to get a histologic diagnosis, which should affect the subsequent therapeutic strategy because metastasis to the ovary meant an inoperable cancer progression. The resected ovary was diagnosed as juvenile granulosa cell tumor, but not Krukenberg tumor. Thus, subsequent curative surgeries, such as thoracolaparotomy for esophagogastric junction cancer and robot-assisted surgery for rectal cancer, were performed. Immunohistochemical examination revealed that the expression of CA19-9 was strongly observed in the tumor of esophagogastric junction, but not in the tumors of rectum or ovary. Furthermore, serum CA19-9 was drastically decreased after the resection of esophagogastric junction cancer. In aggregate, this esophagogastric junction cancer met the criteria of CA19-9-producing gastric cancer defined by Okinaga et al. So far, 46 cases of CA19-9-producing gastric cancer including this case have been reported in Japanese literature. Interestingly, this case had another characteristic of juvenile granulosa cell tumor, one of borderline malignant sex cord-stromal tumors rarely found in adults.
Assuntos
Tumor de Células da Granulosa , Neoplasias Retais , Neoplasias Gástricas , Adulto , Antígeno CA-19-9 , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Tumor de Células da Granulosa/patologia , Tumor de Células da Granulosa/cirurgia , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
The consumption of fruit and vegetables was reported to be associated with a reduced risk of esophageal cancer (EC) in many studies of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) from different regions worldwide. Therefore, to provide precise information to reduce the risk of EC in Asia, we performed a systematic review and meta-analysis of studies conducted in the Asian region about fruit and vegetable consumption and the risk of EC. We searched the MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases from January 2010 to December 2020. The summary relative risk (SRR) and 95% CI were calculated using a random-effects model. In addition, I2 statistics were used to detect heterogeneity. Twenty-two studies were eligible for meta-analysis (16 case-control studies and 6 cohort studies). The SRR for the lowest versus highest fruit consumption was 0.64 (95% CI 0.53-0.77, I2 = 82%). That for the lowest versus highest vegetable consumption was 0.61 (95% CI 0.50-0.74, I2 = 81%). Based on subgroup analysis, a validated Food Frequency Questionnaire (FFQ) was significantly associated (SRR for fruit: 0.54; 95% CI 0.40-0.74, SRR for vegetable: 0.60; 95% CI 0.48-0.76) with low heterogeneity (I2 = 48% for fruit, I2 = 0% for vegetables). Egger's funnel plot asymmetry test demonstrated publication bias (P < 0.001 for fruit, P = 0.009 for vegetables). Fruit and vegetable consumption might be associated with a lower risk of EC in the Asian region. However, further substantial prospective studies with a validated FFQ and well-controlled important confounding factors are required to confirm the association.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/prevenção & controle , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Comportamento Alimentar , Frutas , Humanos , Estudos Prospectivos , VerdurasRESUMO
Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34-7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57-2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.
Assuntos
Consumo de Bebidas Alcoólicas , Neoplasias Esofágicas , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/prevenção & controle , Humanos , Incidência , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagoscopia/métodos , Humanos , Invasividade Neoplásica/patologiaRESUMO
BACKGROUND: The prognosis of patients with gastric cancer and positive peritoneal lavage cytology is poor, even after gastrectomy. Though the standard therapy for this population is radical gastrectomy followed by S-1 chemotherapy, treatments vary among institutions and eras. We conducted a multicenter retrospective study to investigate the prognostic factors for cytology-positive gastric cancer. METHODS: We reviewed the medical records obtained from 6 institutions, covering 2000-2019. There were 128 patients with positive cytology and no other distant metastases that underwent R1 gastrectomy. Univariate and multivariate analyses to identify prognostic factors for overall survival were conducted using Cox's proportional hazards models. RESULTS: The median overall survival time was 18.6 months. In univariate analyses, age (≥ 80 years vs. < 70 years), performance status (2, 3 vs. 0), prognostic nutritional index (< 35 vs. ≥ 40), the extent of lymphadenectomy (D1 vs. ≥ D2), macroscopic type (type 4 vs. non-type 4), and postoperative chemotherapy (none vs. S-1) were significantly correlated with worse survival. Multivariate analysis revealed that lymph node metastasis (pN3b vs. pN0, hazard ratio 4.46, 95% confidence interval 1.17-16.9, p = 0.03) and postoperative chemotherapy (none vs. S-1, hazard ratio 2.28, 95% confidence interval 1.16-4.45, p = 0.02) were independent risk factors for death. No postoperative chemotherapy regimen showed a survival benefit over S-1 monotherapy. CONCLUSIONS: Massive lymph node metastasis was an independent risk factor in cytology-positive gastric cancer. Postoperative chemotherapy was also an independent prognostic factor, though the most beneficial regimen was still uncertain.
RESUMO
PURPOSE: Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients. METHODS: We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the "preoperative EI" and the maximum as the "peak EI". RESULTS: A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026). CONCLUSION: The EI is possibly a predictive marker for perioperative water management in cardiac surgery.
Assuntos
Água Corporal/metabolismo , Impedância Elétrica , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/cirurgia , Assistência Perioperatória , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Edema/diagnóstico , Edema/etiologia , Edema/prevenção & controle , Espaço Extracelular/metabolismo , Feminino , Taxa de Filtração Glomerular , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Espaço Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Valor Preditivo dos Testes , Estudos Retrospectivos , RiscoRESUMO
OBJECTIVES: The first aim of this study was to elucidate the detection rate of esophagogastroduodenoscopy (EGD) in patients complaining of dysphagia with esophageal motility disorders; the second was to clarify the useful parameters of EGD associated with esophageal motility disorders. METHODS: Participants included 380 patients who underwent EGD before high-resolution manometry (HRM) for dysphagia. EGD findings were investigated according to the following five parameters: resistance when passing through the esophagogastric junction (EGJ), residue in the esophageal lumen, esophageal dilation, and spastic and nonocclusive contractions. HRM diagnoses were based on the Chicago classification (v3.0). RESULTS: The percentage of abnormal EGD findings was 64.4% among patients with esophageal motility disorders, and the results differed for each esophageal motility disorder. The rate of abnormal EGD for both EGJ outflow obstruction and major disorders of peristalsis was significantly higher than that for manometrically normal subjects. On multivariate analysis, resistance when passing through EGJ, residue in the esophageal lumen, spastic and nonocclusive contraction were significantly associated with esophageal motility disorders. The sensitivity, specificity, positive predictive value, and negative predictive value of these parameters for detection of esophageal motility disorders were 75.1%, 86.6%, 84.8% and 77.8%, respectively. CONCLUSION: Esophagogastric junction outflow obstruction and major disorders of peristalsis can be screened with EGD. Among several endoscopic parameters, resistance when passing through EGJ, residue in the esophageal lumen, spastic and nonocclusive contraction are considered significantly useful indicators.
Assuntos
Transtornos da Motilidade Esofágica , Chicago , Endoscopia do Sistema Digestório , Transtornos da Motilidade Esofágica/diagnóstico , Junção Esofagogástrica , Humanos , ManometriaRESUMO
Medullary carcinoma of the colorectum is a relatively new histological subtype that was first described in the eighth edition of the Japanese classification of colorectal, appendiceal, and anal carcinoma. In our institution, only 3 cases of medullary carcinoma have been diagnosed since 2013. Case #1 was a 93-year-old woman with type 1 ascending colon cancer; she received a right hemicolectomy. The tumor invaded the subserosal layer, but no lymph nodal metastasis was observed. Case #2 was a 91-year-old woman with obstructive ascending colon cancer. After intracolonic decompression using the transnasal ileus tube, she received a right hemicolectomy. This tumor also extended into the subserosal layer without lymph nodal metastasis. Case #3 was a 65-year-old woman with a family history of cancers; she received a right hemicolectomy for cecal cancer with an aberrant elevation of serum tumor markers such as CEA and CA19-9. The tumor invaded the subserosal layer with regional lymph nodal metastases. Notably, these 3 cases were females who had right-sided tumors and all showed diminished expressions of MLH1 and PMS2 mismatch repair-associated genes, together with epidemiological characteristics of medullary carcinoma. Herein, we report their pathological features along with the corresponding literature review.
Assuntos
Adenocarcinoma , Carcinoma Medular , Neoplasias do Colo , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/cirurgia , Reparo de Erro de Pareamento de DNA , Feminino , HumanosRESUMO
The PI3K-AKT pathway is expected to be a therapeutic target for non-small cell lung cancer (NSCLC) treatment. We previously reported that a novel PI3K inhibitor iMDK suppressed NSCLC cells in vitro and in vivo without harming normal cells and mice. Unexpectedly, iMDK activated the MAPK pathway, including ERK, in the NSCLC cells. Since iMDK did not eradicate such NSCLC cells completely, it is possible that the activated MAPK pathway confers resistance to the NSCLC cells against cell death induced by iMDK. In the present study, we assessed whether suppressing of iMDK-mediated activation of the MAPK pathway would enhance anti-tumorigenic activity of iMDK. PD0325901, a MAPK inhibitor, suppressed the MAPK pathway induced by iMDK and cooperatively inhibited cell viability and colony formation of NSCLC cells by inducing apoptosis in vitro. HUVEC tube formation, representing angiogenic processes in vitro, was also cooperatively inhibited by the combinatorial treatment of iMDK and PD0325901. The combinatorial treatment of iMDK with PD0325901 cooperatively suppressed tumor growth and tumor-associated angiogenesis in a lung cancer xenograft model in vivo. Here, we demonstrate a novel treatment strategy using iMDK and PD0325901 to eradicate NSCLC.
Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cumarínicos/farmacologia , Difenilamina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Tiazóis/farmacologia , Animais , Linhagem Celular Tumoral , Difenilamina/farmacologia , Sinergismo Farmacológico , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Neovascularização Patológica/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A 23-year-old man with a history of anemia of unknown cause was referred to our hospital. He had experienced melena three times: at 6 months, 10 years, and 20 years of age. He underwent upper and lower gastrointestinal endoscopy at 10 and 20 years of age, and small intestinal capsule endoscopy twice at 20 years of age, but the site of bleeding could not be identified. At first, a transabdominal ultrasound was performed for suspected Meckel's diverticulum. A cystic diverticulum was found in the ileum, with an apertural diameter of 5 mm and a total size of 4 cm. The cyst showed an area of loss of wall stratification, which appeared to be an ulcer scar. Based on these observations, we diagnosed anemia resulting from a hemorrhagic Meckel's diverticulum and performed laparoscopic resection. Postoperative histopathology revealed ectopic gastric mucosa and ulcer formation within the Meckel's diverticulum, which was thought to be the cause of the bleeding. Meckel's diverticulum should be considered in cases of hemorrhage in young patients. A transabdominal ultrasound as a screening test detected a diverticulum with an ulcer scar in the ileum, which led to the identification of the underlying disease.
RESUMO
Among mucus-producing lung cancers, invasive mucinous adenocarcinoma of the lung is a rare and unique subtype of pulmonary adenocarcinoma. Notably, mucus production may also be observed in the five subtypes of adenocarcinoma grouped under the higher-level diagnosis of Invasive Non-mucinous Adenocarcinomas (NMA). Overlapping pathologic features in mucus-producing tumors can cause diagnostic confusion with significant clinical consequences. In this study, we established lung tumoroids, PDT-LUAD#99, from a patient with NMA and mucus production. The tumoroids were derived from the malignant pleural effusion of a patient with lung cancer and have been successfully developed for long-term culture (> 11 months). Karyotyping by fluorescence in situ hybridization using an alpha-satellite probe showed that tumoroids harbored aneuploid karyotypes. Subcutaneous inoculation of PDT-LUAD#99 lung tumoroids into immunodeficient mice resulted in tumor formation, suggesting that the tumoroids were derived from cancer. Xenografts from PDT-LUAD#99 lung tumoroids reproduced the solid adenocarcinoma with mucin production that was observed in the patient's metastatic lymph nodes. Immunoblot analysis showed MUC5AC secretion into the culture supernatant of PDT-LUAD#99 lung tumoroids, which in contradistinction was barely detected in the culture supernatants of NCI-A549 and NCI-H2122 pulmonary adenocarcinoma cells known for their mucin-producing abilities. Here, we established a novel high-mucus-producing lung tumoroids from a solid adenocarcinoma. This preclinical model may be useful for elucidating the pathogenesis of mucus-producing lung cancer.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Mucina-5AC , Muco , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Muco/metabolismo , Animais , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mucina-5AC/metabolismo , Mucina-5AC/genética , Camundongos , Linhagem Celular Tumoral , Células Tumorais Cultivadas , Masculino , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismoRESUMO
Approximately 3-5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. There are only a few reports on cell lines with EML4-ALK variant 3 (v3) and tumoroids that can be subject to long-term culture (> 3 months). In this study, we established tumoroids (PDT-LUAD#119) from a patient with lung cancer harboring EML4-ALK that could be cultured for 12 months. Whole-exome sequencing and RNA sequencing analyses revealed TP53 mutations and an EML4-ALK v3 mutation. PDT-LUAD#119 lung tumoroids were sensitive to the ALK tyrosine kinase inhibitors (ALK TKIs) crizotinib, alectinib, entrectinib, and lorlatinib, similar to NCI-H3122 cells harboring EML4-ALK variant 1 (v1). Unexpectedly, clear squamous cell carcinoma and solid adenocarcinoma were observed in xenografts from PDT-LUAD#119 lung tumoroids, indicating adenosquamous carcinoma. Immunostaining revealed that the squamous cell carcinoma was ALK positive, suggesting a squamous transformation of the adenocarcinoma. Besides providing a novel cancer model to support basic research on ALK-positive lung cancer, PDT-LUAD#119 lung tumoroids will help elucidate the pathogenesis of adenosquamous carcinoma.
Assuntos
Quinase do Linfoma Anaplásico , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Proteínas de Fusão Oncogênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Transformação Celular Neoplásica/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Crizotinibe/farmacologia , Linhagem Celular Tumoral , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologiaRESUMO
Pulmonary large-cell neuroendocrine carcinoma (LCNEC), a disease with poor prognosis, is classified as pulmonary high-grade neuroendocrine carcinoma, along with small-cell lung cancer. However, given its infrequent occurrence, only a limited number of preclinical models have been established. Here, we established three LCNEC tumoroids for long-term culture. Whole-exome sequencing revealed that these tumoroids inherited genetic mutations from their parental tumors; two were classified as small-cell carcinoma (S-LCNEC) and one as non-small cell carcinoma (N-LCNEC). Xenografts from these tumoroids in immunodeficient mice mimicked the pathology of the parent LCNEC, and one reproduced the mixed-tissue types of combined LCNEC with a component of adenocarcinoma. Drug sensitivity tests using these LCNEC tumoroids enabled the evaluation of therapeutic agent efficacy. Based on translational research, we found that a CDK4/6 inhibitor might be effective for N-LCNEC and that Aurora A kinase inhibitors might be suitable for S-LCNEC or LCNEC with MYC amplification. These results highlight the value of preclinical tumoroid models in understanding the pathogenesis of rare cancers and developing treatments. LCNEC showed a high success rate in tumoroid establishment, indicating its potential application in personalized medicine.