RESUMEN
BACKGROUND: Regorafenib(Rego)is the salvage line standard treatment for metastatic colorectal cancer(mCRC), which often causes severe toxicities, such as hand-foot syndrome. Previously, we reported that in phase â ¡ study, S-1 plus bevacizumab( Bev)(SB)showed favorable anticancer activity and feasibility as a salvage line. The aim of this study was to evaluate 2 treatments for mCRC as salvage line. PATIENTS AND METHODS: In this multicenter phase â ¡ study, the patients were randomly assigned(1:1)to the Rego or SB group. In the Rego group, Rego 160 mg/kg body weight was orally administered every 28 days for 21 days. In the SB group, S-1 was orally administered every 42 days for 28 days, according to body surface area, and Bev 5 mg/kg was administered by intravenous infusion on days 1, 15, and 29. Administration of S-1 every 21 days for 14 days and Bev 7.5 mg/kg on day 1 was also permitted. The primary endpoint was overall survival(OS), and the planned sample size was 86. RESULTS: This study was ended prematurely due to poor accrual. Overall, 8 patients were enrolled from 6 institutions between Oct 2013 and May 2015. Although 4 patients were assigned to each group, one patient in the Rego group was excluded after enrollment. The median OS in the Rego and SB groups was 30.2 months and 6.6 months, respectively(hazard ratio: 0.205, p=0.123). The median progression-free survival in the Rego and SB groups was 3.7 months and 1.6 months, respectively. The disease control rate in the Rego and SB groups was 100% and 75%, respectively. The Grade 3 or 4 adverse events were increased, including AST/ALT(n=1, 25%), hyponatremia(n=1, 25%), hand-foot syndrome(n=1, 25%), hypertension(n=1, 25%), and proteinuria(n=1, 25%)in the Rego group and colitis( n=1, 25%)in the SB group; the treatment was discontinued. CONCLUSION: Despite the fact that data could only be collected from a small number of patients, SB is not recommended as salvage line for mCRC.
Asunto(s)
Neoplasias Colorrectales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Compuestos de Fenilurea/uso terapéutico , PiridinasRESUMEN
Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin ß1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin ß1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High-level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Integrina beta1/metabolismo , Neovascularización Patológica/metabolismo , Nexinas de Clasificación/metabolismo , Inductores de la Angiogénesis/metabolismo , Membrana Celular/metabolismo , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Integrinas/metabolismo , Neovascularización Patológica/genética , Transporte de Proteínas/fisiologíaRESUMEN
BACKGROUND: Elderly patients usually have concurrent ailments, and the safety and effectiveness of laparoscopy-assisted distal gastrectomy (LADG) for these patients have been controversial. This study aimed to evaluate whether laparoscopy-assisted distal gastrectomy is safe and effective for elderly patients aged 80 years and over, as well as to clarify their long-term prognosis. METHODS: A total of 31 patients aged 80 years and over who underwent LADG in our hospital were retrospectively reviewed. Peri- and postoperative data were compared with those of 38 patients aged 65 years and younger. The median follow-up period of the elderly and younger group was 56.0 and 63.0 months, respectively, and their prognosis was examined. RESULTS: There were significant differences between the two groups in preoperative respiratory and renal functions, hemoglobin, and nutritional index. Significant differences in postoperative complications were seen only in pneumonia and delirium. There were no hospital deaths, but the 3-year and 5-year overall survival rates were significantly lower in the elderly group than in the non-elderly group. However, in the elderly group, only one patient died of gastric cancer recurrence, whereas four died of cardiovascular disease and three died of pneumonia during follow-up. Therefore, the recurrence-free survival rate was not significantly different between the groups. CONCLUSIONS: LADG seems to be safe and effective even for elderly patients, and their prognosis was satisfactory. However, careful monitoring for cardiovascular and pulmonary disease should be observed during the follow-up period.
Asunto(s)
Gastrectomía/métodos , Laparoscopía/métodos , Neoplasias Gástricas/cirugía , Adulto , Factores de Edad , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Gastrectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Since general thoracic surgery requires a short fasting period, the number of cases that require nutrition support after surgery is limited and few reports exist about nutrition in general thoracic surgery and chronic empyema. Here we report 2 cases of chronic empyema treated with nutritional support team (NST) followed by omentopexy. For chronic empyema, a long period is required to sterilize the thoracic cavity by closed or open drainage before radical treatment. During this period, improvement of the nutrition status is important to control local infection, and to increase the volume of the omentum or muscle flaps used for filling the empyema space effectively. In our 2 cases, radical surgeries using omental flap were successfully performed after the improvement of general condition by aggressive nutritional support.
Asunto(s)
Empiema/cirugía , Apoyo Nutricional/métodos , Epiplón/cirugía , Enfermedades Peritoneales/cirugía , Anciano , Enfermedad Crónica , Empiema/complicaciones , Femenino , Humanos , Masculino , Enfermedades Peritoneales/complicaciones , Infecciones Estreptocócicas/complicacionesRESUMEN
A rectovaginal fistula (RVF) is an abnormal tract between the rectum and vagina, which requires surgical intervention in many cases. Although there are many different therapeutic approaches for RVF depending on the patient's' condition, there are no established guidelines for the care of RVF. This study aimed to evaluate the results of laparoscopic colostomy in advanced cancer patients with RVF, and the safety and efficacy of this surgery. In this study, seven female advanced cancer patients with RVF were hospitalized and successfully treated with laparoscopic colostomy from 2015 to 2018 at our university hospital. Their data were retrospectively evaluated from their medical records. The early use of diverting stomas facilitated timely resumption of cancer treatment and enabled early treatment with chemotherapy or radiotherapy. Although vaginal stool leakage affected three patients, all patients recovered, experiencing neither pain nor infection during their cancer treatment. While colostomy was physically and mentally taxing for the patients, it improved the infection and pain caused by the RVF. We conclude that the early use of diverting stomas had two effects: a significant improvement in infection management and facilitation of the rapid resumption of cancer treatment.
RESUMEN
Primary mediastinal liposarcomas are rare malignancies, comprising fewer than 1% of all mediastinal tumors. We herein report a radical resection of a massive liposarcoma arising from the anterior mediastinum. A 63-year-old male patient presented with a 4-week history of dyspnea that had worsened over the previous several days. The patient had also experienced hoarseness for 2 weeks. Chest X-ray and computed tomography revealed a huge tumor occupying the entire left thoracic cavity. Anesthesia was induced when the patient was in the left semilateral position. The patient was moved into the right lateral position after initially stabilizing anesthesia with separate lung ventilation. The fourth rib was initially resected for thoracotomy, but there was no clearance between the tumor and the adjacent mediastinal structures, and two more ribs were therefore removed. The tumor had not invaded the other structures such as the chest wall, lung, or mediastinum. To reduce the tumor blood flow, the left internal mammary artery was ligated before the tumor was resected en bloc. The tumor was diagnosed as a liposarcoma arising from the thymus. The patient remains alive with no evidence of disease recurrence at 22 months after the operation.
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Liposarcoma/cirugía , Neoplasias del Mediastino/cirugía , Cavidad Torácica/cirugía , Tratamiento de Urgencia , Humanos , Liposarcoma/diagnóstico por imagen , Masculino , Neoplasias del Mediastino/diagnóstico por imagen , Persona de Mediana Edad , Cavidad Torácica/patología , Toracotomía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The increasing age of patients with severe motor and intellectual disabilities (SMID) has become a serious concern. Few studies have investigated tumor treatment in this population. METHODS: Tumor treatments for 12 SMID patients were examined. RESULTS: Blood tests and ultrasonography were useful for screening. With regard to treatment, surgery for SMID patients was performed in the same manner as for patients without SMID, and the results were generally satisfactory, without major complications. Typically, cancer was diagnosed at an advanced stage, and many metachronous double cancers were observed. CONCLUSIONS: Treatment yielded satisfactory results for patients with SMID and their families. Future studies should examine the clinical significance of screening and tumor operative method for patients with SMID.
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Discapacidad Intelectual , Predicción , Humanos , Incidencia , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/epidemiologíaRESUMEN
Rubinstein-Taybi syndrome is an extremely rare autosomal dominant genetic disorder that occurs in 1/125,000 and is characterized by distinctive facial appearance, short stature, mild to severe mental retardation, and higher risk for cancer. In addition, variable organ anomalies had been reported. Paraovarian cyst causing torsion of the ipsilateral fallopian tube is less common, with an estimated incidence of 1/1,500,000, but it can adversely affect tubal function. It occurs mainly in women in the reproductive age and is very rare in prepubescent girls. Here, we described the successful treatment of an extremely rare case of paraovarian cyst causing torsion of the ipsilateral fallopian tube in a patient with Rubinstein-Taybi syndrome. A 14-year-old girl with Rubinstein-Taybi syndrome was referred to our hospital for abdominal pain. Her medical history was unremarkable, except for moderate hirsutism and keloid scar. Physical examination revealed tenderness in the lower abdominal midline. The preoperative diagnosis was torsion of a left ovarian cyst. An exploratory laparoscopy was performed because of acute abdominal pain and revealed a left fallopian tube that was twisted twice due to an ipsilateral paraovarian cyst. The huge paraovarian cyst required laparotomy cystectomy, and the left ovary was preserved. Her postoperative course was uncomplicated. Preoperative diagnosis of paraovarian cysts can be difficult. The moderate hirsutism seen in our patient suggested the presence of a large paraovarian cyst due to androgen receptor-mediated effects. Therefore, Rubinstein-Taybi syndrome patients with hirsutism should be screened and assessed by pediatric surgeons for the presence of paraovarian cysts.
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Dolor Abdominal/etiología , Enfermedades de las Trompas Uterinas/diagnóstico por imagen , Ovariectomía/métodos , Quiste Paraovárico/cirugía , Síndrome de Rubinstein-Taybi/complicaciones , Adolescente , Cistectomía , Enfermedades de las Trompas Uterinas/cirugía , Femenino , Hirsutismo , Humanos , Queloide , Laparoscopía , Laparotomía , Quiste Paraovárico/diagnóstico por imagen , Síndrome de Rubinstein-Taybi/diagnóstico , Anomalía Torsional/diagnóstico por imagen , Anomalía Torsional/etiología , Anomalía Torsional/cirugía , Resultado del TratamientoRESUMEN
Wilms tumor (WT) is the most common malignant kidney tumor in children. High blood pressure is seen in up to 55% of children with WT. However, hypertensive cardiomyopathy with congestive heart failure due to WT is remarkably rare, with only several cases reported worldwide. In this report, a pediatric case of WT with hypertension causing hypertensive cardiomyopathy and congestive heart failure is presented. An 8-month-old male child with abdominal distension was seen by his primary physician. He was referred to our hospital for further examination and treatment. Abdominal contrast-enhanced computed tomography demonstrated a weakly enhancing, large abdominal mass, which was larger than 12 cm. Two-dimensional transthoracic echocardiography showed a diffuse hypokinetic left ventricle. The patient was diagnosed with cardiomyopathy caused by hypertension. Open surgical resection of the mass was successfully performed. His postoperative course was uncomplicated, and the patient was successfully discharged. The plasma renin activity was maintained at a high level even after left nephrectomy, suggesting that the right kidney was likely the source of renin secretion. Mechanical compression of the right renal blood vessels by a greatly enlarged left kidney can cause right renal ischemia, which activates renin excretion. Nephrectomy can be an effective treatment for a WT patient with hypertension causing hypertensive cardiomyopathy, and then cardiac function will be improved within several weeks. We recommend routine echocardiography surveillance in patients with WT. This report can help pediatric surgeons become more familiar with cardiomyopathy caused by WT.
Asunto(s)
Cardiomiopatías/diagnóstico , Insuficiencia Cardíaca/etiología , Hipertensión/complicaciones , Renina/sangre , Tumor de Wilms/complicaciones , Cardiomiopatías/etiología , Niño , Humanos , Lactante , Neoplasias Renales/complicaciones , Neoplasias Renales/cirugía , Masculino , Tumor de Wilms/sangre , Tumor de Wilms/cirugíaRESUMEN
Obstructive colitis (OC) is a nonspecific inflammatory condition that occurs at the proximal side of a completely or partially stenotic lesion typically caused by colorectal cancer. Impaired blood flow caused by these stenotic changes in the colon or rectum results in this condition. During surgery for sigmoid colon carcinoma with OC, complete surgical removal of the OC lesions is required. However, it is difficult to anticipate the range of OC before surgery. Diagnosing the potential ischemia during surgery would decrease the need for re-operation. This is the first report of HyperEye Medical System (HEMS) angiography for surgery of colon cancer with OC. We report a case of sigmoid colon carcinoma in which HEMS angiography was used and found to be useful for real-time detection of the OC lesion.
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Angiografía/métodos , Colitis/diagnóstico por imagen , Colitis/cirugía , Colon/irrigación sanguínea , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/cirugía , Isquemia/diagnóstico , Márgenes de Escisión , Recto/irrigación sanguínea , Neoplasias del Colon Sigmoide/irrigación sanguínea , Neoplasias del Colon Sigmoide/cirugía , Anciano , Colitis/etiología , Colitis/fisiopatología , Humanos , Verde de Indocianina , Obstrucción Intestinal/etiología , Obstrucción Intestinal/fisiopatología , Periodo Intraoperatorio , Masculino , Neoplasias del Colon Sigmoide/complicaciones , Neoplasias del Colon Sigmoide/diagnóstico por imagenRESUMEN
Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is related to numerous pathophysiological events. We previously reported that a RING ubiquitin ligase complex scaffold protein, cullin-3 (CUL3), and one of its adaptor proteins, BAZF, regulated angiogenesis in the mouse retina by suppressing Notch signaling. However, the degree of inhibition of angiogenesis was made greater by CUL3 depletion than by BAZF depletion, suggesting other roles of CUL3 in angiogenesis besides the regulation of Notch signaling. In the present study, we found that CUL3 was critical for the cell surface level of integrin ß1, an essential cell adhesion molecule for angiogenesis in HUVECs. By siRNA screening of 175 BTBPs, a family of adaptor proteins for CUL3, we found that ANKFY1/Rabankyrin-5, an early endosomal BTBP, was also critical for localization of surface integrin ß1 and angiogenesis. CUL3 interacted with ANKFY1 and was required for the early endosomal localization of ANKFY1. These data suggest that CUL3/ANKFY1 regulates endosomal membrane traffic of integrin ß1. Our results highlight the multiple roles of CUL3 in angiogenesis, which are mediated through distinct CUL3-adaptor proteins.