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Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.
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Proteínas Cromosómicas no Histona/metabolismo , Neoplasias Gástricas , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Roturas del ADN de Doble Cadena , Daño del ADN , Reparación del ADN , Inestabilidad Genómica , Recombinación Homóloga , Humanos , Recombinasa Rad51/metabolismo , Reparación del ADN por Recombinación , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Background: Transumbilical laparoscopic appendectomy (TULA) may be a feasible alternative to conventional laparoscopic appendectomy. However, a transumbilical incision may increase incisional surgical site infections (SSIs) compared to conventional laparoscopic appendectomy. This study aimed to investigate the relationship between the morphology of the umbilicus and the incidence of SSIs in patients who underwent TULA. Patients and Methods: This retrospective study analysed the medical records of consecutive patients who underwent surgery for acute appendicitis at our institution from June 2016 to October 2020. The patients were assigned to the SSI group (those with an SSI) or the non-SSI group. The morphology of the umbilicus was calculated by measuring its width and depth on preoperative computed tomography images and was compared between the SSI and non-SSI groups. Results: The SSI group included 23 patients, while the non-SSI group included 252 patients. The width of the umbilicus was significantly shorter in the SSI group than in the non-SSI group (29 ± 10 mm vs. 34 ± 9 mm, P = 0.027). The umbilicus was slightly deeper in the SSI group than in the non-SSI group; however, the difference was not significant (16 mm vs. 15 mm, P = 0.384). Conclusions: This was the first study investigating the correlation between the morphology of the umbilicus and SSI development in TULA. SSIs tended to occur more commonly in a narrow and deep umbilicus. An extension of the umbilical incision may help prevent SSI in patients with this umbilical morphology.
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Background and objectives: Single-port laparoscopic appendectomy (SLA) in most previous studies has used intracorporeal excision of the appendix and needed a longer operative time than multi-port laparoscopic appendectomy (MLA), although SLA does have the potential benefit of an almost invisible scar within the umbilicus. Some studies have reported that extracorporeal transumbilical single-incision laparoscopic-assisted appendectomy (TULAA) in children took a considerably reduced operative time compared to MLA. We adopted TULAA in adults, adding routine dissection of the peritoneal attachment of the appendix. The aim was to compare the operative outcomes between TULAA and MLA. Materials and Methods: Between March 2013 and January 2016, 770 patients with acute uncomplicated and complicated appendicitis from 15 to 75 years of age were enrolled retrospectively. The operation was performed as early (EA) and interval appendectomy (IA). Results: Operative time was shorter in the TULAA group than in the MLA group, except for IA. No open conversion occurred in the TULAA group, except one case of ileocecal resection for IA. No intra-abdominal fluid collection was found in the TULAA group. Extended resection (especially partial cecectomy) was performed less frequently in the TULAA group than in the MLA group for IA. Mean postoperative hospital stay was shorter in the TULAA group for uncomplicated appendicitis. When the data of the EA group and the IA group were compared, operative time was significantly shorter in the IA group for both MLA and TULAA. The open conversion rate and the complication rate tended to be lower in the IA group. Confined to IA, the TULAA group tended to have shorter mean initial, postoperative, and total hospital stays. Conclusions: TULAA can be a useful surgical alternative to MLA in adults and young adolescents, because it lacks open conversion and provides both a shorter operative time and a shorter postoperative hospital stay. TULAA is feasible for IA in that it showed a lower rate of extended resection and complications.
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Apendicectomía/métodos , Laparoscopía/métodos , Ombligo/cirugía , Adolescente , Adulto , Apendicectomía/instrumentación , Apendicitis/cirugía , Femenino , Humanos , Laparoscopía/instrumentación , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , República de Corea , Estudios Retrospectivos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
BACKGROUND: Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer. METHODS: Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1-7 of every 2-week cycle. RESULTS: Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1-31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6-74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6-14.0) and 15.4 months (95% CI 12.6-18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%). CONCLUSION: These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02527785.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Pueblo Asiatico , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Irinotecán/administración & dosificación , Masculino , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVES: With the aging population, the number of elderly patients diagnosed with gastric cancer is increasing. However, determining treatment strategies for elderly patients with gastric cancer is controversial. The aim of this study is to evaluate the usefulness of surgical treatment on elderly patients aged ≥80 years with advanced gastric cancer. METHODS: A total of 147 elderly patients who were diagnosed with advanced gastric cancer from August 2001 to December 2015 were retrospectively analyzed. We compared the clinicopathological features and prognoses of 94 elderly patients (80-85 years) and 53 extreme-elderly patients (≥86 years) according to treatment modalities. RESULTS: In the elderly group, the 3-year overall survival (OS) rates of the surgical resection group and supportive care group were 42.1% and 4.0%, respectively (p < .001). In the extreme-elderly group, the 3-year OS rates of the surgical resection group and supportive care group were 36.4% and 8.0%, respectively (p = .028). The post-operative mortality rate of the elderly group and extreme-elderly group was 5.6% and 9.1%, respectively. In the analysis of risk factors associated with survival, surgical resection was a significantly good prognostic factor in the elderly group (hazard ratio [HR] = 0.277; p = .003) compared with supportive care. In the extreme-elderly group, surgical resection was associated with good prognosis but did not reach statistical significance (HR = 0.491; p = .099). CONCLUSIONS: These results suggest that elderly patients aged 80-85 years with advanced gastric cancer could expect a better prognosis with surgical resection. However, extreme-elderly patients aged ≥86 years should consider the risks and benefits of surgical treatment.
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Gastrectomía , Escisión del Ganglio Linfático , Neoplasias Gástricas/cirugía , Factores de Edad , Anciano de 80 o más Años , Femenino , Gastrectomía/mortalidad , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/terapia , Tasa de SupervivenciaRESUMEN
OBJECTIVE: For subepithelial tumours (SETs) of the stomach, surgical resection is the gold standard treatment. With the recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative treatment for SETs. The aim of our study was to evaluate the clinical outcomes of ESD for treating gastric SETs compared with surgical resection. METHODS: Between January 2006 and September 2014, 55 patients with gastric SETs (13 gastrointestinal stromal tumours (GISTs), 27 leiomyomas, and 15 others) were treated by ESD and 27 patients (19 GISTs, two leiomyomas, and six others) underwent surgical resection. We retrospectively reviewed the therapeutic outcomes, procedure-related complications, post-procedure hospital stays, and medical costs of the two groups. RESULTS: The complete resection rate of the ESD group was lower than that of the surgery group (81.8% vs. 100%, p = 0.026). Although the incidence of complications that occurred with ESD was higher than that associated with surgical resection, there were no significant between-group differences (12.5% vs. 3.7%, p = 0.261), and all complicated cases were successfully treated without mortality. The ESD group had significantly shorter post-procedural hospital stays (median five days vs. eight days, p = 0.034) and lower medical costs (median $2374 vs. $4954, p <0.001) than the surgery group. There were no recurrences in either group during the follow-up period. CONCLUSIONS: ESD is an efficient treatment tool for gastric SETs in selected patients. Additionally, ESD has the advantages of shorter hospital stays and lower medical costs compared with surgery.
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Disección/métodos , Mucosa Gástrica/cirugía , Tumores del Estroma Gastrointestinal/cirugía , Gastroscopía/métodos , Neoplasias Gástricas/cirugía , Adulto , Endosonografía , Femenino , Estudios de Seguimiento , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/patología , Tumores del Estroma Gastrointestinal/diagnóstico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , República de Corea/epidemiología , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. METHODS: Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m(2) and oxaliplatin at 105 mg/m(2) were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m(2) on days 1-14 of every 21-day cycle. RESULTS: Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively. CONCLUSION: These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Administración Intravenosa , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Taxoides/administración & dosificación , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Robotic surgery is increasingly used for rectal cancer. We compared the short- and long-term outcomes between robotic- and laparoscopic-assisted resection for rectal cancer. METHODOLOGY: A retrospective chart review was performed between 2006 and 2010. RESULTS: Seventeen robotic and 61 laparoscopic surgeries were performed consecutively. Median follow-up time was 58.2 months. No operation was converted to open surgery. No difference was observed between the groups for types of operations, diverting ileostomy rate, operation time, blood loss, and postoperative hospital stay, tumor diameter, distal margin, circumferential margin, tumor stage, differentiation, lymphovascular, or perineural invasion. However, the number of harvested lymph nodes was higher in the robot than that in the laparoscopy group (p = 0.017). Overall morbidity and reoperation rates were similar between the groups. The 5-yr overall and disease-free survival rates of all patients were 82.5% and 81.3%, respectively. The 5-yr overall and disease-free survival rates of the robotic and the laparoscopy groups were 94.1% and 79.7% (p = 0.241), and 94.1% and 77.9% (p = 0.159), respectively. CONCLUSIONS: Robot-assisted resection for rectal cancer resulted in harvesting more lymph nodes without increasing morbidity and showed a comparable survival rate, compared with those of laparoscopy.
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Laparoscopía/métodos , Neoplasias del Recto/cirugía , Robótica , Cirugía Asistida por Computador , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Laparoscopía/efectos adversos , Laparoscopía/mortalidad , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de Riesgo , Cirugía Asistida por Computador/efectos adversos , Cirugía Asistida por Computador/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Varicose vein incompetence in the legs is very prevalent in the Korean population. New technologies and improvements in established methods have changed the treatment of varicose veins. Transilluminated powered phlebectomy is an alternative surgical technique that combines endoscopic powered vein resection and ablation of superficial varicosities with tumescent anesthesia and irrigated illumination. The present study sought to determine the clinical efficacy and safety of transilluminated powered phlebectomy from clinical data. METHOD: Four hundred and forty-seven limbs in 299 patients (157 male, 142 female; mean age 50.6 years) with varicose veins were treated with transilluminated powered phlebectomy over a 7-year period. The patients were followed for 1 year postoperatively. The analyzed data included sex, age, body mass index, operative time (from skin incision to the application of elastic bandages on the legs for compression purposes), and postoperative complications. RESULTS: The mean operative time was 87.2 min for both limbs and 57.3 min for single limbs. The median number of incisions was five. Postoperative complications included an episode of cellulitis in 10 patients (2.2%), wound abscess in two patients (0.4%), hematoma in 15 patients (3.4%), residual veins in five patients (1.1%), cutaneous nerve damage in 10 patients (2.2%), and seroma in 13 patients (2.9%). No skin perforation and deep venous thrombosis were observed at the 1-year follow-up. CONCLUSION: Transilluminated powered phlebectomy is an effective and safe method for the excision of varicosities.
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Transiluminación/métodos , Várices/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Acute spontaneous vertigo with idiopathic sudden sensorineural hearing loss (ISSNHL) can be diagnosed as labyrinthitis, which has a poorer prognosis than ISSNHL without vertigo. Thus, we aimed to identify the effect of the baseline vestibular function on the prognosis of labyrinthitis. METHODS: A total of 23 patients with labyrinthitis was retrospectively divided into the recovered group (complete recovery, partial recovery) and the nonrecovered group (slight improvement, no improvement). Differences in caloric weakness and gain in the video head impulse test (vHIT) between the two groups were compared. In addition, the prognostic value of the vHIT on each of the three semicircular canals in predicting hearing recovery was analyzed using a linear regression model. RESULTS: In final pure-tone audiometry, 2 patients (8.70%) exhibited complete recovery, 4 patients (17.39%) had partial recovery, and 17 patients (73.91%) had slight or no improvement. The initial ipsilesional posterior canal (iPC) gain and the contralesional anterior canal (cAC) gain were significantly decreased in the nonrecovered group (p < 0.013 for iPC and p < 0.007 for cAC, Mann-Whitney U test). The mean hearing gain was positively correlated with the iPC gain (R2 = 0.36, p = 0.003, Spearman correlation analysis). CONCLUSION: An abnormal iPC gain may be a poor prognostic factor for hearing recovery. Additionally, the vHIT on the three semicircular canals can provide prognosis and insights into the pathophysiological mechanisms in patients with labyrinthitis.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Laberintitis , Humanos , Estudios Retrospectivos , Prueba de Impulso Cefálico , Vértigo , Canales Semicirculares , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Laberintitis/complicaciones , PronósticoRESUMEN
Vestibular schwannoma (VS) originates from Schwann cells in the superior or inferior vestibular nerve. Identifying the precise origin will help in determining the optimal surgical approach. We retrospectively analyzed the preoperative vestibular function test according to VS origin to determine whether the test is a valuable indicator of tumor origin. Forty-seven patients with VS (male:female = 18:29, mean age: 54.06 ± 13.50 years) underwent the cochleovestibular function test (pure-tone audiometry, caloric test, video head impulse test (vHIT), cervical and ocular vestibular-evoked myogenic potential, and posturography). All patients then underwent surgical removal of VS, and the schwannoma origin was confirmed. The tumor originated from the superior vestibular nerve (SVN group) in 21 patients, the inferior vestibular nerve (IVN group) in 26 patients, and an undetermined site in eight patients. The only value that differed significantly among the groups was the gain of the vestibular-ocular reflex (VOR) in the ipsilesional posterior canal (iPC) during the vHIT. Our results indicate that VOR gain in the iPC may be used to predict the nerve origin in patients with VS. Other cochleovestibular function tests have limited value to discriminate nerve origins, especially in cases of medium to large VS.
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Background: Abnormal regulation of genes has been closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. In our study, we used RNA sequencing analyses to show that on gastric cancer tissues to identification of gastric cancer prognostic markers. We specifically chose to study RNF43 because it inhibits gastric cancer-related Wnt/ß-catenin signaling by interacting with Wnt receptors. PWWP2B was chosen because it is a gene which is downregulated in gastric cancer. Methods: Utilizing RNA sequencing analysis, we evaluated the mRNA expression profile in gastric cancer patients. Also, we used HAP1 cells which is a human near-haploid cell line derived from the male chronic myelogenous leukemia cell line KBM-7. These cell line has one copy of each gene, ensuring the edited allele will not be masked by additional alleles. We investigated the screening of 1,449 FDA-approved drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells. RNA sequencing data reveals that RNF43 and PWWP2B expression were down-regulated in recurrence gastric cancer patients. Next, we investigated the anti-cancer effects of selected drugs in RNF43 and PWWP2B down-regulated MKN45 gastric cancer cells and xenograft model. Results: Among these FDA-approved drugs, three drugs (docetaxel trihydrate, pelitinib and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. In MKN45 xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group. Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer. Conclusions: Our findings suggest that docetaxel trihydrate, uprosertib and pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with a decrease in RNF43 and PWWP2B expression.
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BACKGROUND: This retrospective study aimed to evaluate the ability of the delta neutrophil index (DNI) to predict histologically normal appendicitis preoperatively and to differentiate between simple and complicated appendicitis. METHODS: The data from 650 patients were divided into positive and negative appendectomy groups (histologically normal appendicitis). The patients in the acute appendicitis group were further sub-divided into simple and complicated appendicitis groups. RESULTS: The DNI was significantly higher in the positive group than in the negative appendectomy group (0.4 vs. -0.4, p < 0.001) as well as in the complicated group compared with that in the simple appendicitis group (1.2 vs. 0.3, p < 0.001). The DNI independently predicted a positive appendectomy and an acute complicated appendicitis in multivariate logistic regression analysis [odds ratio (OR) 2.62, 95% confidence interval (CI) (1.11~6.16), p = 0.028 and odds ratio (OR) 4.10, 95% confidence interval (CI) (2.94~5.80), p < 0.001]. The optimum cut-off for a positive appendectomy and acute complicated appendicitis were 0.2 [area under curve (AUC) 0.709] and 0.6 (AUC 0.727). CONCLUSIONS: We suggest that obtaining a preoperative DNI is a useful parameter to aid in the diagnosis of histologically normal appendicitis and to differentiate between simple and complicated appendicitis.
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Apendicitis/diagnóstico , Técnicas de Apoyo para la Decisión , Neutrófilos , Adulto , Apendicectomía/métodos , Apendicitis/fisiopatología , Biomarcadores/análisis , Biomarcadores/sangre , Femenino , Humanos , Recuento de Leucocitos/métodos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios RetrospectivosRESUMEN
PURPOSE: Single incision laparoscopic cholecystectomy (SILC) is generally performed with the use of inverse triangulation. In this study, we performed 3-channel or 4-channel SILC without the use of inverse triangulation. We evaluated the adequacy and feasibility of SILC using our surgical method. METHODS: We retrospectively reviewed our series of 309 SILCs performed between March 2014 and February 2015. RESULTS: Among 309 SILCs, male were 148 and female were 161 patients, mean age was 48.7 ± 15.3 years old and mean body mass index was 24.8 ± 3.8 kg/m(2). Forty patients had previously undergone abdominal surgery including 6 cases of upper abdominal surgery. SILC after percutaneous transhepatic gallbladder (GB) drainage was completed in 8.7% of cases. There were 10 cases of emergency SILC. SILC was performed for noncomplicated GB including symptomatic GB stone and polyp in 66.7% of cases, acute cholecystitis in 33.3%. Overall, 96.8% of procedures were successfully completed without additional port. The reason for addition of an extra port or open conversion included technical difficulties due to severe adhesion and bleeding. The mean operating time was 60.7 ± 22.3 minutes. The overall complication rate was 4.8%: 9 patients of wound seroma, 1 case of bile leakage from GB bed, 4 cases of intra-abdominal abscess or fluid collection, and 1 case of incisional hernia were developed. There was no case of common bile duct injury. CONCLUSION: Our surgical method of SILC without the use of inverse triangulation is safe, feasible and effective technique.
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PURPOSES: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer. METHODS: Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1-7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m2; level 2, 85/120/80 mg/m2; level 3, 85/120/100 mg/m2; level 4, 85/150/100 mg/m2; and level 5, 85/180/100 mg/m2. Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity. RESULTS: Twenty-four patients were enrolled between October 2012 and February 2014 (median age 59 years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6 %. CONCLUSIONS: The combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan, and 100 mg/m2 of S-1 every 2 weeks.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Administración Intravenosa , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Humanos , Irinotecán , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Ácido Oxónico/administración & dosificación , Tegafur/administración & dosificación , Resultado del TratamientoRESUMEN
Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1-22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82-5.80) months and 6.24 (95% CI, 1.44-11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients.
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Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers. The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target. However, molecular profiles of A-ACs and their prognostic impact are poorly understood. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper were used to detect KRAS, BRAF, and PIK3CA mutations in 62 paraffinized samples of A-ACs. Of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation. Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis. Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors. Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs. Different therapeutic protocols should be considered for treating pancreatobiliary- and intestinal-type A-ACs.
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Adenocarcinoma/genética , Ampolla Hepatopancreática , Biomarcadores de Tumor/genética , Neoplasias del Conducto Colédoco/genética , Mutación , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Diferenciación Celular , Fosfatidilinositol 3-Quinasa Clase I , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/terapia , Análisis Mutacional de ADN/métodos , Supervivencia sin Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , República de Corea , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: We conducted this pooled analysis to investigate the impact of RECIST 1.1 on the selection of target lesions and classification of tumor response, in comparison with RECIST 1.0. Methods : We searched MEDLINE and EMBASE for articles with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual meeting presentations from the conferences of ASCO and ESMO between 2009 and 2013. RESULTS: There were six articles in the literature comparing the clinical impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total of 359 patients were recruited from the six trials; 217 with non-small cell lung cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid cancer. The number of target lesions by RECIST 1.1 was significantly lower than that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed high concordance with RECIST 1.0 in the assessment of tumor responses (k = 0.903). Sixteen patients (4.8%) showed disagreement between the two criteria. CONCLUSION: This pooled study demonstrated that RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in patients with metastatic cancer.
RESUMEN
BACKGROUND: The RECIST 1.1 adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. Recently, we reported that the modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a high level of concordance with the original RECIST 1.1 in patients with advanced or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and colorectal cancer (CRC). However, each study had a major limitation of a small number of patients. METHODS: We conducted a pooled analysis using the data from the three individual studies to improve statistical power. Tumor responses were compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1). RESULTS: A total of 153 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51 with GC, and 38 with CRC. Regardless of primary sites, the number of target lesions according to the mRECIST 1.1 was significantly lower than that according to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high concordance between the two criteria (k = 0.908). Only eight patients (5.2%) showed disagreement in the tumor response assessment between the two criteria. The overall response rates of chemotherapy were not significantly different between the two criteria (33.3% versus 33.3%, P=1.0). CONCLUSIONS: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response in clinical practice.
RESUMEN
PURPOSE: A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). METHODS: Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m(2) intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m(2) oral S-1 on days 1-14 of each cycle. The treatment was repeated every 3 weeks. RESULTS: Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6%), intrahepatic and extrahepatic bile ducts in 23 (60.5%), and the ampulla of Vater in 3 (7.9%) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6% (95% CI 8.5-36.7] in the per-protocol (PP) population, and 18.4% (95%CI 6.1-30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5% (95%CI 60.6-87.6) in the PP population. The median progression-free survival was 4.4 months (95%CI 1.8-6.9), and the median overall survival was 9.0 months (95%CI 4.0-13.9) with a 1-year survival rate of 44.7% (95%CI 29.0-61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1%), 9 (25.7%), 2 (5.7%), and 2 (5.7%) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4%), anorexia (2.9%), and renal toxicity (2.9%). CONCLUSION: Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.