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1.
Langenbecks Arch Surg ; 408(1): 452, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38032404

RESUMO

PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.


Assuntos
Parede Abdominal , Hérnia Incisional , Aumento de Peso , Feminino , Humanos , Peso Corporal , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
2.
Acta Med Okayama ; 68(4): 249-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25145411

RESUMO

We describe an extremely rare case of tracheal stenosis caused by unnoticed microscopic fiber-like foreign bodies. A 66-year-old woman complained of dyspnea with inspiratory stridor. Magnifying electroendoscopy and computed tomography revealed stenosis involving the entire circumference of the tracheal lumen. Tracheotomy and biopsy were performed. Histologically, the lesion showed chronic inflammation with a deposition of fiber-like foreign bodies. The patient had no history of trauma or inhalation injury, but had undergone intratracheal intubation on 4 occasions. The lesion was incised using semiconductor laser photoresection, and the postoperative course was good. To the best of our knowledge, this represents the first report in the English literature of tracheal stenosis caused by unnoticed foreign bodies. The origin of these fiber-like foreign bodies remains unclear but might be related to chronic inflammation resulting from intratracheal intubations.


Assuntos
Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico , Intubação Intratraqueal/efeitos adversos , Estenose Traqueal/diagnóstico , Estenose Traqueal/etiologia , Idoso , Feminino , Corpos Estranhos/patologia , Humanos , Estenose Traqueal/cirurgia
3.
Mol Clin Oncol ; 20(3): 17, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38292013

RESUMO

Nivolumab monotherapy is a standard treatment of metastatic gastric cancer, and this type of cancer involves vascular endothelial growth factor (VEGF) signaling in the tumor immunological environment. The subgroup analysis of the ATTRACTION-2 trial revealed that prior treatment with ramucirumab (RAM), a VEGF inhibitor, affected the therapeutic effect of nivolumab. The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. A total of 29 patients with metastatic gastric cancer were treated with PTX + RAM as second-line treatment, followed by nivolumab monotherapy as third-line treatment. The therapeutic efficacy of nivolumab was compared in 13 patients with progression-free survival (PFS) of <5 months and 16 patients with PFS ≥5 months after PTX + RAM therapy. The present study included 22 male and seven female patients, with a median age of 68 years (range, 45-82 years). Human epidermal growth factor receptor 2 positivity was observed in six patients. The disease control rate was 62.1%. The PFS and overall survival (OS) were 4.4 and 11.9 months, respectively. Patients with PFS ≥5 months after PTX + RAM therapy showed better outcome in both PFS (5.3 months vs. 2.8 months, P=0.039) and OS (6.9 months vs. 15.2 months, P=0.066) after nivolumab treatment than patients with PFS of <5 months after PTX + RAM therapy. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer.

4.
J Hosp Infect ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950864

RESUMO

BACKGROUND: While seasonality of hospital-acquired infections, including incisional SSI after orthopaedic surgery, is recognized, the seasonality of incisional SSI after general and gastroenterological surgeries remains unclear. STUDY DESIGN: This retrospective single-institute observational study analysed the seasonality and risk factors of incisional SSI after general and gastroenterological surgeries using univariate and multivariable analyses. The evaluated variables included age, sex, surgical approach, surgical urgency, operation time, wound classification, and the American Society of Anesthesiologists physical status (ASA-PS). RESULTS: 8,436 patients were enrolled. General surgeries (n=2,241) showed a pronounced SSI incidence in summer (3.9%; odds ratio [OR] 1.87; 95% confidence interval [CI] 1.05-3.27; p=0.025) compared to other seasons (2.1%). Conversely, gastroenterological surgeries (n=6,195) showed a higher incidence in winter (8.3%; OR 1.38; 95% CI 1.10-1.73; p=0.005) than in other seasons (6.1%). Summer for general surgery (OR 1.90; 95% CI 1.12-3.24; p=0.018) and winter for gastroenterological surgery (OR 1.46; 95% CI 1.17-1.82; p=0.001) emerged as independent risk factors for incisional SSI. Open surgery (OR, 2.72; 95% CI 1.73-4.29, p<0.001) and an ASA-PS score ≥3 (OR, 1.64; 95% CI 1.08-2.50, p=0.021) were independent risk factors for incisional SSI in patients undergoing gastroenterological surgery during winter. CONCLUSION: Seasonality exists in the incisional SSI incidence following general and gastroenterological surgeries. Recognizing these trends may help enhance preventive strategies, highlighting the elevated risk in summer for general surgery and in winter for gastroenterological surgery.

5.
Trials ; 25(1): 327, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760769

RESUMO

BACKGROUND: The recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure. The wound closure technique is an important determinant of the risk of wound complications, and a comprehensive approach to prevent wound complications should be developed. METHODS: We propose a single-institute, prospective, randomized, blinded-endpoint trial to assess the superiority of the combination of continuous suturing of the fascia without peritoneal closure and continuous suturing of the subcuticular tissue (study group) over that of interrupted suturing of the fascia together with the peritoneum and interrupted suturing of the subcuticular tissue (control group) for reducing the incidence of midline abdominal wall incision wound complications after elective gastroenterological surgery with a clean-contaminated wound. Permuted-block randomization with an allocation ratio of 1:1 and blocking will be used. We hypothesize that the study group will show a 50% reduction in the incidence of wound complications. The target number of cases is set at 284. The primary outcome is the incidence of wound complications, including incisional surgical site infection, hemorrhage, seroma, wound dehiscence within 30 days after surgery, and incisional hernia at approximately 1 year after surgery. DISCUSSION: This trial will provide initial evidence on the ideal combination of fascial and skin closure for midline abdominal wall incision to reduce the incidence of overall postoperative wound complications after gastroenterological surgery with a clean-contaminated wound. This trial is expected to generate high-quality evidence that supports the current guidelines for the closure of abdominal wall incisions from the European and American Hernia Societies and to contribute to their next updates. TRIAL REGISTRATION: UMIN-CTR UMIN000048442. Registered on 1 August 2022. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055205.


Assuntos
Parede Abdominal , Técnicas de Fechamento de Ferimentos Abdominais , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Eletivos , Hérnia Incisional , Infecção da Ferida Cirúrgica , Técnicas de Sutura , Humanos , Estudos Prospectivos , Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos , Parede Abdominal/cirurgia , Técnicas de Sutura/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Hérnia Incisional/prevenção & controle , Hérnia Incisional/etiologia , Hérnia Incisional/epidemiologia , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Resultado do Tratamento , Incidência , Cicatrização , Estudos de Equivalência como Asunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
6.
J Infect Chemother ; 19(6): 1015-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23839859

RESUMO

Cervical tuberculous lymphadenitis is mainly diagnosed by analyzing tissue samples obtained by fine-needle aspiration (FNA). However, some cases remain diagnostic challenges even after polymerase chain reaction analysis of FNA specimens. To delineate differences between cases that are relatively easy to diagnose and those for which diagnosis is difficult, 22 patients with cervical tuberculous lymphadenitis were studied retrospectively. FNA tissues were used to diagnose 14 cases (group A), whereas excisional biopsy was required for accurate diagnosis of 8 cases (group B). These two groups were compared with regard to results of blood examinations, ultrasound appearance, and various other procedures required to reach the final diagnosis. The results indicated that diagnosis of cervical tuberculous lymphadenitis was more difficult for patients with lower white blood cell counts, lower serum C-reactive protein levels, and absence of lymph node fusion or abscess formation on ultrasonography. The possibility of tuberculosis as a cause of cervical lymphadenopathy should always be considered, even when the presenting symptoms are not typical of this disease.


Assuntos
Tuberculose dos Linfonodos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose dos Linfonodos/diagnóstico por imagem , Tuberculose dos Linfonodos/patologia , Ultrassonografia , Adulto Jovem
7.
J Surg Case Rep ; 2022(7): rjac218, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35919698

RESUMO

Treatment strategies for corrosive esophagitis include conservative treatment, such as balloon dilatation at the stenosis site, and surgical treatment. Esophagectomy for corrosive esophagitis is usually performed through the transthoracic or transhiatal approaches. Herein, we report a case of corrosive esophagitis treated with thoracoscopic esophagectomy with the patient in the semi-prone position. The patient was a 48-year-old woman who developed corrosive esophagitis due to accidental ingestion of an alkaline agent. Surgical intervention was required for esophageal stenosis. Therefore, thoracoscopic esophagectomy was performed with the patient in the semi-prone position with bilateral pulmonary ventilation. In our hospital, good operative outcomes have been obtained using thoracoscopic esophagectomy for esophageal cancer with the patient in the semi-prone position with bilateral pulmonary ventilation. This technique is also considered effective for the treatment of corrosive esophagitis.

8.
Sci Rep ; 12(1): 20710, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456615

RESUMO

Gastric and bile acid reflux leads to chronic inflammation, resulting in methylation alterations in Barrett's esophagus (BE) together with chromosomal instability (CIN). We investigated DNA hypomethylation following acid exposure and confirmed its significance in BE-related carcinogenesis by inducing CIN in vitro. OACP4C, an esophageal cancer cell line, and CP-A, a non-dysplastic cell line originating from BE, were exposed to acidic conditions using deoxycholic acid. CP-A exhibited substantially increased DNA hypomethylation of alpha satellite sequences in the centromere region, as well as increased levels of alpha satellite transcripts, but no changes were observed in the long interspersed nucleotide element-1 sequences distributed throughout the entire genome. These changes were not clearly found in OACP4C. Copy number changes at specific chromosomes were identified in CP-A, along with an increased number of cells exhibiting abnormal segregations, whereas these changes were rarely observed in OACP4C. The changes were maintained after several cell divisions. These findings suggest that alpha satellites are likely targets of DNA hypomethylation induced by acid exposure. CP-A was more sensitive to acid exposure than OACP4C, indicating that acid-induced DNA hypomethylation is involved in cancer development rather than progression, which could be involved in the underlying mechanism of esophagogastric junction carcinoma development.


Assuntos
Esôfago de Barrett , Ácidos e Sais Biliares , Humanos , Linhagem Celular , Instabilidade Cromossômica , Células Epiteliais , Esôfago de Barrett/genética , Junção Esofagogástrica , DNA
9.
Mol Clin Oncol ; 16(5): 103, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35463210

RESUMO

Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m2) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.

10.
Sci Rep ; 12(1): 10999, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768614

RESUMO

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability (CIN) through the DNA damage response and cell cycle checkpoint activation. Although satellite RNAs may be therapeutic targets, the associated mechanisms underlying drug sensitivity are unknown. Here, we determined whether satellite RNAs reflect drug sensitivity to the topoisomerase I inhibitor camptothecin (CPT) via CIN induction. We constructed retroviral vectors expressing major satellite and control viruses, infected microsatellite stable mouse colon cancer cells (CT26) and MC38 cells harboring microsatellite instability, and assessed drug sensitivity after 48 h. Cells overexpressing satellite RNAs showed clear features of abnormal segregation, including micronuclei and anaphase bridging, and elevated levels of the DNA damage marker γH2AX relative to controls. Additionally, overexpression of satellite RNAs enhanced MC38 cell susceptibility to CPT [half-maximal inhibitory concentration: 0.814 µM (control) vs. 0.332 µM (MC38 cells with a major satellite), p = 0.003] but not that of CT26. These findings imply that MC38 cells, which are unlikely to harbor CIN, are more susceptible to CIN-induced CPT sensitivity than CT26 cells, which are characterized by CIN. Furthermore, CPT administration upregulated p53 levels but not those of p21, indicating that overexpression of major satellite transcripts likely induces CPT-responsive cell death rather than cellular senescence.


Assuntos
Heterocromatina , Neoplasias , Animais , Camptotecina/farmacologia , Instabilidade Cromossômica , Dano ao DNA , Heterocromatina/genética , Camundongos , RNA Satélite
11.
Int J Oncol ; 60(6)2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35419613

RESUMO

Genome­wide DNA hypomethylation is the most common molecular feature in human cancers associated with chromosomal instability (CIN), which is involved in the mechanisms that regulate pancreatic cancer (PC) metastasis. It was investigated whether genome­wide DNA hypomethylation affects the phenotype in PC via CIN in vitro, and its significance on the biological behavior of PC was verified. The relative demethylation level (RDL) of long interspersed nucleotide element­1 (LINE­1) in human PC cell lines was used to characterize DNA hypomethylation using methylation­specific quantitative (q)PCR. CIN was estimated by changes in chromosomal copy number using comparative genomic hybridization analysis. Abnormal segregation of chromosomes was assessed by immunocytochemistry, and the DNA damage response was evaluated using the number of anti­Î³H2AX positive cells. Invasion ability was assessed using a Matrigel invasion assay. Clinical specimens from 49 patients with PC who underwent curative surgery were evaluated for a correlation of DNA hypomethylation with clinical outcome. Successful induction of genome­wide DNA hypomethylation in PC cells led to copy number changes in specific chromosomal regions. The number of cells with abnormal segregation of chromosomes significantly increased with the number of anti­Î³H2AX positive cells. The invasive potential of these cells also significantly increased. The occurrence of occult distant metastasis in the clinical specimens and receiver operating characteristic analysis clearly identified those who were and were not likely to have occult distant metastasis, with high LINE­1 RDL significantly correlated with the presence of occult distant metastasis (P=0.035) and poor prognosis (P=0.048). The significance of genome­wide DNA hypomethylation on the biological behavior of PC, which promotes a more invasive phenotype via CIN in vitro and predicts the susceptibility to occult distant metastasis and poor prognosis in patients with PC was revealed.


Assuntos
Metilação de DNA , Neoplasias Pancreáticas , Instabilidade Cromossômica/genética , Hibridização Genômica Comparativa , DNA , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Fenótipo , Prognóstico , Neoplasias Pancreáticas
12.
Sci Rep ; 11(1): 20797, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675229

RESUMO

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.


Assuntos
Antígeno CA-19-9/sangue , Carcinoma Ductal/patologia , DNA Tumoral Circulante/sangue , Mutação , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Carcinoma Ductal/sangue , Carcinoma Ductal/genética , Feminino , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Prognóstico , Análise de Sobrevida
13.
J Surg Case Rep ; 2020(1): rjz367, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31976058

RESUMO

We report a rare case of adult intussusception caused by an inverted Meckel's diverticulum with ectopic pancreatic tissue. A 43-year-old woman was referred to our hospital with complaints of abdominal distention, intermittent abdominal pain and nausea that she experienced 3 months ago. Abdominal computed tomography scans demonstrated ileo-ileal intussusception that contained a tumor with fat density as the lead point. Laparoscopic-assisted partial resection of the small intestine was performed. The surgical specimen showed an elongated polypoid lesion invaginated into the intestinal tract indicating an inverted Meckel's diverticulum. Pathological findings showed a true diverticulum that ran antimesentrically, with tall columnar epithelium, a mucous gland and an islet of Langerhans. The postoperative period was uneventful, and she was discharged on the ninth postoperative day.

14.
Int J Surg Case Rep ; 64: 143-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655284

RESUMO

INTRODUCTION: Swallowing a corrosive substance causes delayed gastrointestinal stenosis due to scar formation. Here, we report on our use of esophageal bypass using a supercharged pedicled jejunal flap to treat cicatricial esophageal stenosis caused by corrosive esophagitis. PRESENTATION OF CASE: Nineteen years before presentation, a 57-year-old man had swallowed a chemical cleaning agent, which caused extensive corrosive cicatricial stenosis from the thoracic upper esophagus to the gastric fornix. An enterostomy had been created, and the patient had since been subsisting on enteral nutrition. However, he wanted to be able to eat through his mouth again and was referred to our department for treatment. With the exception of the cervical esophagus, circumferential cicatricial stenosis was present throughout the esophagus and gastric fornix, with severe adhesions to the surrounding tissue. It was decided not to perform esophagectomy but to perform esophageal bypass surgery using a supercharged pedicled jejunal flap. DISCUSSION: Despite the extremely high risk of cancer in the stenotic esophagus due by corrosive esophagitis, indicating that esophagectomy should be performed if possible, we chose to perform bypass surgery because the severe adhesions posed a high risk of early injury to the surrounding organs. CONCLUSION: We suggest that esophageal bypass using pedicled jejunal pull-up "supercharging" by creating anastomoses between the jejunal and internal thoracic vessels is the optimal procedure for patients with extensive cicatricial esophageal stenosis caused by corrosive esophagitis.

15.
Surg Case Rep ; 5(1): 145, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637554

RESUMO

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed. CASE PRESENTATION: A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment. CONCLUSIONS: This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.

16.
PLoS One ; 14(12): e0227366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31891652

RESUMO

BACKGROUND: Liquid biopsies enable the detection of circulating tumor DNA (ctDNA). However, the clinical significance of KRAS-mutated ctDNA for pancreatic cancer has been inconsistent with respect to its prognostic and predictive potential. METHODS AND FINDINGS: A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS mutation in tissues and KRAS ctDNA levels in plasma were determined by RASKET and droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and for evaluating therapeutic responses to chemotherapy compared with carbohydrate antigen 19-9 (CA19-9). In 67 tumor tissues, discrepancies in point mutations of KRAS were rarely observed among individual patients, implying that one targeted point mutation of KRAS can be determined in tumor tissues prior to longitudinal blood monitoring. One-time blood assessment of KRAS-mutated ctDNA before surgery or chemotherapy was not clearly associated with recurrence and prognosis. Sequential blood monitoring was performed in 39 patients who underwent surgery for potentially resectable tumors. Increased CA19-9 levels were significantly associated with recurrence, but not prognosis (P<0.001, P = 1.0, respectively), whereas emergence of KRAS ctDNA was significantly associated with prognosis (P<0.001) regardless of recurrence. Furthermore, in 39 patients who did not undergo surgery, detection of KRAS ctDNA was a predictive factor for prognosis (P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA was the only independent prognostic factor regardless of tumor resection (hazard ratios = 54.5 for patients who underwent surgery and 10.1 for patients who did not undergo surgery; P<0.001 for both). Patients without emergence of KRAS ctDNA within 1 year after surgery showed significantly better prognosis irrespective of recurrence (P<0.001). No detection or disappearance of KRAS ctDNA within 6 months of treatment was significantly correlated with therapeutic responses to first-line chemotherapy (P<0.001). Changes in KRAS status provided critical information for the prediction of therapeutic responses. CONCLUSIONS: Our study showed for the first time that detection of KRAS ctDNA levels within a short period enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Mutação , Prognóstico , Resultado do Tratamento
17.
Oncol Rep ; 42(2): 857-865, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173247

RESUMO

Patients with breast cancer who undergo surgery have a risk of developing multiple cancers in the contralateral breast and other organs. We previously reported that overexpression of satellite alpha transcripts (SAT) facilitates chromosomal instability, which is involved in the development of multiple tumors in patients with colorectal and gastric cancer. In this study, we elucidated the significance of SAT in the development of multiple tumors in patients with breast cancer. Relative expression of SAT (rSAT) was calculated in normal and tumor tissues from 167 patients. In total, 27 patients developed bilateral breast cancer (BBC) and 27 patients showed multiple primary cancer (MPC), with patients with BBC and MPC showing higher rSAT levels in tumor tissues than those in patients with single breast cancer (SBC) (P=0.0312 and P=0.0420, respectively). Additionally, higher rSAT levels in tumor tissues from patients with BBC were a significant factor according to univariate analysis, and multivariate analysis showed that rSAT >1.5 was a significant predictor of MPC [hazard ratio (HR): 2.96; P=0.0243); however, we did not clarify the involvement of SAT in normal tissues. Excluding 71 patients with BRCA­related clinical features, rSAT levels were higher in patients with BBC and MPC than in patients with SBC in tumor tissues and normal tissues (P<0.05). Significant predictors according to univariate analysis included rSAT >1.5 in tumor tissues, rSAT >2.4 in normal tissues, and T <2, whereas those for multivariate analysis included rSAT >2.4 in normal tissues for BBC (HR: 22.7; P=0.00120) and MPC (HR: 13.0; P=0.00601). Our data indicated that patients with breast cancer and high rSAT levels in their breast tissues exhibit a 10­ to 20­fold increased risk for the development of multiple cancers when harboring no BRCA­related clinical features.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , DNA Satélite/genética , Variação Genética , Neoplasias Primárias Múltiplas/genética , Sequências Repetitivas de Ácido Nucleico , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Primárias Múltiplas/patologia , Prognóstico , Fatores de Risco
18.
J Gastric Cancer ; 17(2): 186-191, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28680724

RESUMO

The role of nodal station No. 14v (along the superior mesenteric vein) in lymphadenectomy for distal gastric cancer remains elusive. A 73-year-old woman underwent endoscopic submucosal dissection for gastric cancer, and was referred to our division for additional surgery because of pathologically non-curative resection. A laparoscopic distal gastrectomy with D1+ dissection was performed, with a final diagnosis of pT1bN1M0, Stage IB (2 nodal metastases to No. 6). Four months post-surgery, abdominal computed tomography revealed a 14-mm solitary nodule along the superior mesenteric vein. The lesion was excised and pathologically identified as a lymph node metastasis. Adjuvant chemotherapy with tegafur-gimeracil-oteracil potassium (S-1) was administered for the metastasis. Presently the patient survives without recurrence, 5.5 years after the second operation. Our findings suggest that there is lymphatic flow from the No. 6 to the No. 14v nodal station. Some patients with a No. 6 metastasis may benefit from a No. 14v lymphadenectomy, even in early-staged disease.

19.
Anticancer Res ; 37(7): 3685-3692, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668861

RESUMO

BACKGROUND: The role of para-aortic lymph node (PALN) dissection for far-advanced gastric cancer is controversial in patients with clinical PALN positivity who have responded to chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed long-term outcomes of patients with pathologically-positive PALNs who underwent radical gastrectomy. RESULTS: The 3- and 5-year overall survival (OS) rates of 65 pathologically PALN-positive patients who underwent PALN dissection (n=704) were 33.8% and 21.2%, respectively. Multivariable analysis revealed the following poor prognostic factors: nodal involvement around the celiac axis (hazard ratio (HR)=4.04, 95% confidence interval (CI)=1.55-9.63), tumor diameter of ≥120 mm (HR=3.37; 95% CI=1.18-9.63) and ≥3 PALNs involved (HR=2.24; 95% CI=1.21-4.15). Patients with none of these factors survived significantly longer than those with any of these factors (5-year OS=87.5% versus 9.3%, respectively; p<0.001). CONCLUSION: Pathologically PALN-positive patients achieve long survival; however, the indications for PALN dissection should be carefully considered.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
20.
Mol Clin Oncol ; 5(1): 53-56, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27330765

RESUMO

Mesenteric leiomyosarcoma is a rare disease with poor prognosis. Previously, mesenteric leiomyosarcoma was not differentiated from gastrointestinal stromal tumor (GIST), which is the most common mesenchymal tumor of the gastrointestinal tract, and several cases of GIST may have been misclassified as mesenteric leiomyosarcoma. Thus, the actual clinicopathological characteristics of mesenteric leiomyosarcomas remain unclear. We herein describe a case of leiomyosarcoma arising in the descending mesocolon in a patient who developed metachronous liver metastasis. A 76-year-old woman reported a mass in her left upper abdomen. Computed tomography imaging revealed a low-density tumor adjacent to the descending colon. The patient underwent surgery and the tumor was resected along with part of the descending colon. Immunohistochemical differential diagnosis revealed that the tumor was positive for smooth muscle actin and desmin, and negative for CD117 (c-KIT) and S-100, which are characteristic of gastrointestinal leiomyosarcoma. A single liver metastasis developed 24 months after the operation. The patient underwent curative resection of the metastatic lesion. Sixteen months following surgery for the liver metastasis and 40 months after the initial removal of the primary lesion, the patient remains disease-free. The prognosis of leiomyosarcoma remains poor and standardized chemotherapy for this rare disease has not yet been established. Early diagnosis and surgical removal of the tumor is the only potentially curative option for liver metastasis of mesenteric leiomyosarcoma.

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