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We report herein the design and discovery of novel allosteric HIV-1 integrase inhibitors. Our design concept utilized the spirocyclic moiety to restrain the flexibility of the conformation of the lipophilic part of the inhibitor. Compound 5 showed antiviral activity by binding to the nuclear lens epithelium-derived growth factor (LEDGF/p75) binding site of HIV-1 integrase (IN). The introduction of a lipophilic amide substituent into the central benzene ring resulted in a significant increase in antiviral activity against HIV-1 WT X-ray crystallography of compound 15 in complex with the integrase revealed the presence of a hydrogen bond between the oxygen atom of the amide of compound 15 and the hydroxyl group of the T125 side chain. Chiral compound 17 showed high antiviral activity, good bioavailability, and low clearance in rats.
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Diseño de Fármacos , Inhibidores de Integrasa VIH , Integrasa de VIH , VIH-1 , Compuestos de Espiro , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/síntesis química , Inhibidores de Integrasa VIH/química , Integrasa de VIH/metabolismo , VIH-1/efectos de los fármacos , Cristalografía por Rayos X , Ratas , Relación Estructura-Actividad , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Compuestos de Espiro/síntesis química , Animales , Humanos , Regulación Alostérica/efectos de los fármacos , Estructura Molecular , Modelos Moleculares , Sitios de UniónRESUMEN
The NLRP3 inflammasome plays an important role in the defense mechanism of the innate immune system and has recently attracted much attention as a drug target for various inflammatory disorders. Among the strategies for generating the novel chemotype in current drug discovery, scaffold hopping and bioisosteric replacement are known to be attractive approaches. As the results of our medicinal chemistry campaign, which involved exploration of core motifs using a ring closing approach, a five-membered oxazole-based scaffold was identified, and subsequent implementation of bioisosteric replacement led to discovery of a novel chemical class of NLRP3 inflammasome inhibitor bearing the acylsulfamide group. Further optimization of aniline and sulfamide moieties to improve potency in human whole blood assay led to the identification of the orally bioactive compound 32 in the LPS challenge model. Furthermore, compound 32 attenuated kidney injury in adriamycin-induced glomerulonephritis in mice. These investigations indicated that the NLRP3 inhibitor could be a potential therapeutic agent for glomerulonephritis.
RESUMEN
Regorafenib has shown significant survival benefit as a salvage therapy for colorectal cancer; however, its starting dose has been controversial in recent studies. Therefore, we conducted a prospective study on the efficacy and safety of the dose reduction of regorafenib to 120 mg. Patients received 120 mg regorafenib once per day for 3 weeks, followed by a 1-week off-treatment period. The primary endpoint was the investigator-assessed disease control rate (DCR). Sixty patients were registered, and the DCR was 38.3% with a median progression-free survival of 2.5 months (95% confidence interval [CI] 1.9-3.7) and median overall survival of 10.0 months (95% CI 6.9-15.2). Common grade 3-4 adverse events were hand-foot skin reaction and hypertension (20.0% each). The results of administration of 120 mg regorafenib as the starting dose are consistent with reports from prior phase III trials, which used starting doses of 160 mg. This lower initiating dose of regorafenib may be beneficial to certain patient populations. This clinical trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR number UMIN000018968, registration date: 10/09/2015).
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/patología , Estudios Prospectivos , Piridinas/efectos adversos , Compuestos de Fenilurea/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológicoRESUMEN
The development of small molecule inhibitors of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) has drawn research interest for the treatment of cancer. Recently, we reported the discovery of a novel dimeric core small molecule PD-1/PD-L1 inhibitor. In an effort to discover more potent inhibitors, we further explored the dimeric core scaffold. Our investigations of the structure-activity-relationship revealed that introduction of lipophilic substituents onto one of the di-alkoxylated phenyl rings improved binding affinities to PD-L1, and inhibitory activities of PD-1/PD-L1 in cellular assays. Furthermore, conversion of the ether linker part to an olefin linker not only improved binding affinity but also led to slow dissociation binding kinetics. We also explored more potent, as well as downsized, scaffolds. Compounds bearing a linear chain in place of one of the di-alkoxylated phenyl rings exhibited good binding affinity with improved ligand efficiency (LE). Representative compounds demonstrated potent inhibitory activities of PD-1/PD-L1 in the submicromolar range in cellular assays as well as cellular function in the mixed lymphocyte reaction (MLR) assay with efficacy comparable to anti-PD-1 antibody. Our results provide applicable information for the design of more potent inhibitors targeting PD-1/PD-L1 pathway.
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Antineoplásicos/síntesis química , Antígeno B7-H1/química , Neoplasias/tratamiento farmacológico , Acetamidas/química , Apoptosis , Antígeno B7-H1/metabolismo , Cristalografía por Rayos X , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Estructura Molecular , Unión Proteica , Piridinas/química , Transducción de Señal , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , TermodinámicaRESUMEN
PURPOSE: Neoadjuvant chemotherapy (NAC) followed by surgery is a promising treatment strategy for patients with advanced gastric cancer. Severe toxicity associated with the treatment may reduce the dose intensity of chemotherapy, resulting in the effect of chemotherapy being attenuated. Recently, skeletal muscle mass has been reported to be associated with the treatment outcomes of cancer patients. The purpose of this study was to clarify whether pretreatment skeletal muscle mass is a predictor of adverse events as well as the relationship between changes in skeletal muscle mass and adverse events during NAC. METHODS: This study included 41 advanced gastric cancer patients who were treated with NAC followed by surgery. Body composition was assessed before and after NAC. The relationship between the pre-NAC body composition and adverse events was investigated as well as the relationship between changes in body composition and adverse events. RESULTS: Univariate and multivariate analyses revealed that low pre-NAC skeletal muscle mass was the only factor significantly associated with severe diarrhea (p = 0.03). There was no significant difference in body weight before and after NAC, but skeletal muscle mass was significantly reduced after NAC (-5.93 ± 7.69%, p < 0.01). Furthermore, patients who experienced severe diarrhea showed significantly greater relative skeletal muscle decrease than those who did not (p = 0.03). CONCLUSIONS: Pre-NAC low skeletal muscle mass was a useful predictor of severe diarrhea. Prevention of severe adverse events may contribute to maintaining the skeletal muscle mass.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Músculo Esquelético/patología , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/patología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Composición Corporal , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Estado Nutricional , Tamaño de los Órganos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
The development of small molecule inhibitors of PD-1/PD-L1 is eagerly anticipated for treatment of cancer. We focused on the symmetry of the ternary complex structure of reported small molecule ligands and hPD-L1 homodimers, and designed partially- or fully-symmetric compounds for more potent inhibitors. The design of the new compounds was guided by our hypothesis that the designed symmetric compound would induce a flip of sidechain of ATyr56 protein residue to form a new cavity. The designed compound 4 exhibited substantially increased binding affinity to hPD-L1, as well as PD-1/PD-L1 inhibitory activity in physiological conditions. Compound 4 also showed a dose-dependent increase in IFN-γ secretion levels in a mixed lymphocyte reaction assay. These results not only indicate the feasibility of targeting the PD-1/PD-L1 pathway with small molecules, but illustrate the applicability of the symmetry-based ligand design as an attractive methodology for targeting protein-protein interaction stabilizers.
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Antígeno B7-H1/metabolismo , Diseño de Fármacos , Ligandos , Receptor de Muerte Celular Programada 1/metabolismo , Bibliotecas de Moléculas Pequeñas/química , Anticuerpos/inmunología , Anticuerpos/farmacología , Antígeno B7-H1/química , Antígeno B7-H1/inmunología , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Dimerización , Humanos , Interferón gamma/metabolismo , Receptor de Muerte Celular Programada 1/química , Unión Proteica , Bibliotecas de Moléculas Pequeñas/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Resonancia por Plasmón de SuperficieRESUMEN
CASE: A man in his 60s reported upper abdominal pain; close examination revealed a tumor in the body-tail of the pancreas that was suspected to be infiltrating the stomach. Multiple liver lesions(S3, S4)were also detected. Histological examination by EUS-FNA showed poorly-differentiated carcinoma; thus, this case was diagnosed with unresectable pancreatic cancer with liver metastases(cT3, cN1[No. 7], cM1[P0, H1], cStage â £: JPS 7th). After 2 kinds of systemic chemotherapy(9 courses of GEM plus nab-PTX and 9 courses of modified FOLFIRINOX), obvious distant metastases or local progression did not appear and conversion surgery was scheduled. Although a metastatic lesion was identified at S5 of the liver just before the surgery, it was assumed that an R0 resection could be achieved; therefore, the operation(distal pancreatectomy with combined proximal gastrectomy, left adrenalectomy, lymph node dissection, partial hepatectomy of S5, and cholecystectomy)was performed. Histopathological examination showed squamous metaplasia of the epithelial tissue combined with glandular formation. This case was, thus, diagnosed as adenosquamous carcinoma of pancreas. This patient was discharged 90 days after the operation. The patient is still alive 2 years and 2 months since the first diagnosis.
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Carcinoma Adenoescamoso , Neoplasias Pancreáticas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Adenoescamoso/tratamiento farmacológico , Carcinoma Adenoescamoso/cirugía , Gastrectomía , Humanos , Masculino , Pancreatectomía , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugíaRESUMEN
A 78-year-old man who underwent esophagectomy for middle thoracic esophageal squamous cell carcinoma(pT1bN0M0, pStage â )was diagnosed with lymph node recurrence 12 months after the initial surgery. He received chemoradiotherapy(5- fluorouracil plus cisplatin); however, the treatment was terminated at the middle of the treatment course because of progressive disease. He received chemotherapy(docetaxel plus 5-fluorouracil plus cisplatin)as a second-line treatment, which was also canceled due to serious adverse events. Partial response was achieved after the second therapy; therefore, surgical excision was performed. Thirteen months after the second surgery, he was diagnosed with second local recurrence with invasion to the trachea. Another course of chemotherapy(docetaxel[2-weekly]plus 5-fluorouracil plus cisplatin)was administered, which also achieved a partial response. Thus, surgical excision with partial tracheal resection and mediastinal tracheostomy was performed. He has been alive without recurrence for 6 months after the final operation. In case of postoperative solitary lymph node recurrence of esophageal cancer, long-term survival can be expected with multidisciplinary treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/secundario , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Fluorouracilo , Humanos , Ganglios Linfáticos , Metástasis Linfática , Masculino , Recurrencia Local de Neoplasia , TráqueaRESUMEN
BACKGROUND AND PURPOSE: For patients at high risk, such as those with lower-gastrointestinal perforations, it is important to establish a preventive method that reduces the incidence of surgical site infections (SSIs) significantly. We applied negative-pressure wound therapy (NPWT) as part of a delayed primary closure approach to prevent SSIs. This study evaluated the value of this technique. METHODS: We included prospectively 28 patients undergoing abdominal surgery for peritonitis caused by a lower-gastrointestinal perforation between May 2014 and November 2015. Historical controls comprised retrospective data on 19 patients who had undergone primary suturing for managing peritonitis incisions for a lower-gastrointestinal perforation from January to December 2013. RESULTS: We found a significant association between the SSI incidence and the type of incision management (10.7% with NPWT and delayed closure vs. 63.2% with primary suturing; p < 0.001). There was no significant difference between the groups in the length of the hospital stay (22 days for NPWT and delayed closure vs. 27 days for primary suturing; p = 0.45). No severe adverse events were observed related to NPWT. CONCLUSION: The use of NPWT and delayed primary closure was an effective measure for preventing SSI in patients undergoing abdominal surgery for peritonitis caused by lower-gastrointestinal perforation.
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Perforación Intestinal/cirugía , Terapia de Presión Negativa para Heridas , Peritonitis/cirugía , Infección de la Herida Quirúrgica/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Perforación Intestinal/complicaciones , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Terapia de Presión Negativa para Heridas/métodos , Peritonitis/etiología , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Neoadjuvant therapy followed by surgery has been the standard treatment for advanced esophageal cancer. Severe toxicities may influence body composition, including skeletal muscle mass, and increase postoperative complications. The purpose of this study was to evaluate the influence of sarcopenia, changes in body composition, and adverse events during neoadjuvant chemotherapy (NACT) on postoperative complications in esophageal cancer patients. METHODS: A total of 83 patients with esophageal cancer undergoing NACT followed by esophagectomy were included. Body composition was assessed before chemotherapy and before esophagectomy. The relationships between postoperative infectious complications and sarcopenia, changes in body composition, and adverse events during NACT were investigated. RESULTS: Univariate analysis revealed that skeletal muscle loss during NACT, but not preoperative sarcopenia, was significantly higher in the complication (+) group. Febrile neutropenia tended to occur frequently in the complication (+) group. Multivariate analysis demonstrated that skeletal muscle loss was the only factor significantly associated with infectious complications (p = 0.029). Among adverse events, febrile neutropenia was significantly associated with a decrease in skeletal muscle mass. CONCLUSION: Loss of skeletal muscle mass during NACT was a significant risk factor for postoperative infectious complications in patients with esophageal cancer. Prevention of severe adverse events may reduce postoperative infectious complications.
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Quimioradioterapia Adyuvante/efectos adversos , Enfermedades Transmisibles/etiología , Neoplasias Esofágicas/tratamiento farmacológico , Esofagectomía/efectos adversos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/efectos de la radiación , Terapia Neoadyuvante/efectos adversos , Sarcopenia/etiología , Anciano , Anciano de 80 o más Años , Composición Corporal , Neutropenia Febril Inducida por Quimioterapia/etiología , Distribución de Chi-Cuadrado , Enfermedades Transmisibles/diagnóstico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Estadificación de Neoplasias , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/patología , Sarcopenia/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Case 1 is a 68-year-old woman with locally recurrent rectal cancer(LRRC)developed 5 years after resection of primary rectal cancer. The tumor seized right lateral side in pelvic. We performed tumor excision after preoperative chemoradiation comprised external beam radiation with oral S-1(tegafur/gimeracil/oteracil). He has been relapse-free for 3 years 3months after surgery. Case 2 is a 74-year-old man with LRRC developed 2 years after resection of primary rectal cancer. The tumor was located dorsal to anastomosis site in pelvic. We performed abdominoperineal resection for LRRC after preoperative chemoradiation with oral S-1. He has been relapse-free for 2 years. It was suggested that preoperative radiotherapy combined with oral FU for local recurrence after rectal cancer may contribute to distant and local control.
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Neoplasias Pélvicas/terapia , Neoplasias del Recto/terapia , Anciano , Quimioradioterapia , Femenino , Humanos , Masculino , Neoplasias Pélvicas/secundario , Periodo Preoperatorio , Neoplasias del Recto/patología , Recurrencia , Resultado del TratamientoRESUMEN
Regorafenib is an oral multikinase inhibitor; the CORRECTtrial evaluated its efficacy in patients with metastatic colorectal cancer following disease progression with standard therapies. However, regorafenib has toxicities that develop quickly. Few studies have reported the safe dose and usage of regorafenib to avoid these adverse events in Japanese patients. We examined the side effects and safe administration technique of regorafenib in this study. We administered regorafenib to 15 patients with metastatic colorectal cancer following disease progression with standard therapies. Between August 2013 and January 2014, 5 patients received 160 mg oral regorafenib once daily on days 1-21 of a 28 day course(group A). Between February 2014 and July 2015, 10 patients received initiating therapy with 120 mg regorafenib, with the intention of increasing the dose(group B). We retrospectively assessed side effects, number of dose courses, and total dose of regorafenib in both groups. The median dosing course was 5 coureses in group B, which was more than the 1 course in group A. The median total dose was 10,800 mg in group B, which is about 4 times as much as the 2,400 mg in group A. In group B, 7 out of 10 patients (70%)were successful in the dose escalation of regorafenib from 120 to 160 mg daily over 3-5 courses. The disease control rate was 40% in both groups. The rate of adverse events of Grade 3 or higher was 60% in group A, compared to 40% in group B within 2 courses. The overall survival time was 308 days in group B, which was significantly longer than the 168 days in group A. Initiating therapy with 120 mg regorafenib with the intention of increasing the dose improves safety and allows an increase in dosing courses, as well as in the total dose of regorafenib and overall survival time.
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Neoplasias Colorrectales/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Anciano , Neoplasias Colorrectales/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A 67-year-oldman underwent lower anterior resection for rectal cancer andresection of liver metastatic tumor 5 years later. Seven years and 2 months after the initial surgery, a soft tissue mass was detected in the left diaphragm. Further retrospective review of CT scan images showedthat the diaphragmatic tumor was present just before the hepatectomy. Partial resection of the left diaphragm was performed, and no relapse has occurred since then for 2 years. Most cases of diaphragmatic metastasis are considered to arise from dissemination, but we considered this case as more likely to be hematogenous. When surgery is chosen to treat metastatic tumors of colorectal cancer, checking for other metastasis via preoperative imaging andperforming curative resection is important.
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Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Diafragma/patología , Diafragma/cirugía , Neoplasias del Recto/patología , Anciano , Hepatectomía , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Metástasis de la Neoplasia , Neoplasias del Recto/cirugíaRESUMEN
Though recent studies have revealed that stem cells of many tissues are harbored in hypoxic microenvironment, little is known about the relationship between hypoxia and intestinal crypt base, where intestinal stem cells are supposed to exist. In this study, we focused on carbonic anhydrase IX (CA9), a hypoxia-inducible membrane-tethered protein, in normal intestinal crypt base, adenoma and early colorectal cancer. Using surgically resected human colorectal cancer specimen, we searched for the expression pattern and functional association of CA9 in human adult normal intestinal epithelia, adenoma and early colorectal cancer by immunofluorescent and immunohistochemical staining, flow cytometry, and quantitative real-time-polymerase chain reaction. We demonstrated that almost all crypt base slender cells in ileum and crypt base cells with eosinophilic structure in their basal cytoplasm in right and left colon were CA9+ with the ratio of 25 to 40%, and that adenoma and T1 colorectal cancer showed broad expression of CA9. Flow cytometrically sorted CA9+ population showed increased mRNA level of a Wnt signaling factor AXIN2. In conclusion, these observations indicate that CA9 expression in normal crypt base cells has association with intestinal epithelial stemness and CA9 may be involved in the carcinogenesis of colorectal cancer.
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Adenoma/genética , Antígenos de Neoplasias/biosíntesis , Proteína Axina/biosíntesis , Anhidrasas Carbónicas/biosíntesis , Neoplasias Colorrectales/genética , Adenoma/patología , Adenoma/cirugía , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/genética , Proteína Axina/genética , Anhidrasa Carbónica IX , Anhidrasas Carbónicas/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Citometría de Flujo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVES: This study aimed to assess the relation between stent edge restenosis (SER) and the distance from the stent edge to the residual plaque using quantitative intravascular ultrasound. BACKGROUND: Although percutaneous coronary intervention with drug-eluting stents has improved SER rates, determining an appropriate stent edge landing zone can be challenging in cases of diffuse plaque lesions. It is known that edge vascular response can occur within 2 mm from the edge of a bare metal stent, but the distance to the adjacent plaque has not been evaluated for drug-eluting stents. METHODS: A total of 97 proximal residual plaque lesions (plaque burden [PB] >40%) treated with everolimus-eluting stents were retrospectively evaluated to determine the distance from the stent edge to the residual plaque. RESULTS: The SER group had significantly higher PB (59.1 ± 6.1% vs. 51.9 ± 9.1% for non-SER; P = 0.04). Higher PB was associated with SER, with the cutoff value of 54.74% determined using receiver operating characteristic (ROC) curve analysis. At this cutoff value of PB, the distance from the stent edge to the lesion was significantly associated with SER (odds ratio = 2.05, P = 0.035). The corresponding area under the ROC curve was 0.725, and the cutoff distance value for predicting SER was 1.0 mm. CONCLUSION: An interval less than 1 mm from the proximal stent edge to the nearest point with the determined PB cutoff value of 54.74% was significantly associated with SER in patients with residual plaque lesions.
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Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Stents Liberadores de Fármacos/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Placa Aterosclerótica/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Ultrasonografía IntervencionalRESUMEN
We report the case of a 70-year-old man with unresectable advanced gastric cancer because of invasion to the pancreas and multiple liver metastases. He could have continued with fourth-line chemotherapy by controlling intermittent bleeding from the cancer by means of 2 rounds of radiotherapy and trans-arterial embolization. The serum hemoglobin level declined to 4.5 g/dL during second-line chemotherapy. As the venous bleeding from the cancer was difficult to control by endoscopic hemostasis, radiotherapy with 40 Gy/20 fractions was applied to the cancer. We were able to restart chemotherapy after the hemostasis, but 6 months later, the serum hemoglobin level declined to 6.1 g/dL. Additional radiotherapy of 20 Gy/10 fractions was delivered to the tumor, and successful hemostasis was achieved; the serum hemoglobin level reached 7.5 g/dL. However, a contrast-enhanced CT, which was performed 3 weeks later, demonstrated extravasation from the cancer into the gastric cavity. We conducted trans-arterial embolization, and the patient no longer required transfusion. We planned to restart chemotherapy soon, but after 1 month, he died of pneumonia.
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Embolización Terapéutica , Hemorragia Gastrointestinal/terapia , Hemostasis , Neoplasias Gástricas/terapia , Anciano , Arterias , Resultado Fatal , Hemorragia Gastrointestinal/etiología , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Masculino , Neoplasias Gástricas/patologíaRESUMEN
It is sometimes difficult to differentiate between metastatic and primary liver tumors, when the liver tumor occurs simultaneously with a gastric cancer. We encountered a case of resected gastric cancer, which occurred concomitantly with intrahepatic cholangiocarcinoma after S-1 plus cisplatin chemotherapy, in a patient who was previously diagnosed with metastatic liver tumor before treatment. An 80-year-old man was admitted to our hospital because of epigastralgia. Endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper body of the stomach. A plain CT scan showed an irregular, low-density area, which was enhanced by contrast medium in the lateral segment of the liver. We performed an ultrasound- guided needle biopsy, because it was impossible to make a definitive diagnosis by dynamic CT, contrast-enhanced ultrasonography, and MRI. Immunohistochemical analysis for cytokeratin 7/20 resulted in 7 (+)/20 (-) for both the gastric cancer and the liver tumor. Therefore, we diagnosed the patient with gastric cancer, which occurred concomitantly with the metastatic liver tumor, and administered chemotherapy with S-1 plus cisplatin. After 3 courses of the regimen, a reduction in the size of mass was observed in the stomach and the liver. We subsequently performed left hepatectomy and total gastrectomy with lymph node dissection. Microscopic examination revealed the gastric cancer, which occurred simultaneously with the intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and the patient remains well without recurrences.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/cirugía , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Cisplatino/administración & dosificación , Combinación de Medicamentos , Humanos , Masculino , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tegafur/administración & dosificación , Resultado del TratamientoRESUMEN
Skin metastases from esophageal cancer are comparatively rare but have poor prognosis. Here, we report a case of esophageal cancer metastases to the skin. A 70-year-old man was admitted to our hospital for nodules with ulceration in the nose, and biopsy revealed a metastatic carcinoma. FDG-PET indicated FDG accumulation in the skin, liver, and esophagus, while an endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper mid-thoracic esophagus. We diagnosed the patient with metastatic esophageal cancer and administered chemotherapy. Radiation therapy (40 Gy/20 Fr) was simultaneously administered for the tumor in the nose because the patient's quality of life (QOL) decreased daily owing to pain and bleeding caused by metastatic skin cancer. The radiation therapy reduced the size of the tumor in the nose, but the tumor had remained along with the presence of a scar 3 to 6 months after the start of radiation therapy. Radiation effectively promoted the QOL of our patient with skin metastases.
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Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Neoplasias Cutáneas/terapia , Anciano , Carcinoma de Células Escamosas/secundario , Quimioradioterapia , Neoplasias Esofágicas/secundario , Carcinoma de Células Escamosas de Esófago , Resultado Fatal , Humanos , Masculino , Tomografía de Emisión de Positrones , Calidad de Vida , Neoplasias Cutáneas/secundarioRESUMEN
The prognosis of esophageal cancer patients who undergo non-curative resection is very poor. Here, we retrospectively analyzed the factors associated with non-curative resection. Thirty-five patients with cT3 or T4 thoracic esophageal cancer treated with neoadjuvant chemotherapy or chemoradiotherapy followed by esophageal resection were included in this study. Among the 35 patients, 27 underwent curative resection (R0 group), while 8 underwent non-curative resection (R1R2 group). A comparison of the clinicopathological factors between groups revealed no significant differences in presurgical factors. The pathological T factor was significantly deeper in the R1R2 group than in the R0 group (p=0.0086). Histopathological response tended to be higher in the R0 group (p=0.055). An accurate preoperative diagnosis of T factor is important.
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Neoplasias Esofágicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/terapia , Esofagectomía , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Adulto JovenRESUMEN
Approximately 20% of patients develop some complications after gastrectomy. These complications should be treated appropriately to achieve a positive outcome. The records of 6 patients with postoperative intra-abdominal abscesses treated with interventional radiology (IVR) were analyzed. The cause of abscess was anastomotic leakage in 4 patients and contaminated surgery after gastric perforation in 2 patients. Intra-abdominal abscesses were detected on postoperative day 12 (median), and an IVR-guided drainage tube was inserted with a median interval of 1 day. The drainage tube was kept in place for 26 days (median), and patients were discharged 6.5 days (median) after drainage tube removal. No patients were converted to open surgery. Early IVR-guided drainage was essential and effective for intra-abdominal abscess treatment after gastrectomy.