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1.
Anticancer Res ; 40(1): 299-304, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892580

RESUMO

BACKGROUND/AIM: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events. PATIENTS AND METHODS: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis. RESULTS: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042). CONCLUSION: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Rim/fisiopatologia , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/metabolismo , Feminino , Humanos , Incidência , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Fatores de Risco , Adulto Jovem
2.
Int J Clin Oncol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31807967

RESUMO

BACKGROUND: Regorafenib is a multiple tyrosine kinase inhibitor, and the use of this drug is approved for the treatment of cancers that are resistant to chemotherapy, which include advanced colorectal cancer, gastrointestinal stromal tumor, and hepatocellular carcinoma. However, the drug causes adverse events, including skin toxicities that require dose modification in approximately 75% of cases. At present, the blood concentration of regorafenib is not assessed in clinical settings; thus, we recently developed a method that can assess the blood concentration of the drug using high-performance liquid chromatography. METHODS: We measured the trough blood concentrations (Ctrough) of regorafenib and its metabolites (M2 and M5) in 14 and 4 patients with advanced colorectal cancer and gastrointestinal stromal tumor, respectively, using high-performance liquid chromatography. Then, the correlation between the Ctrough and therapeutic outcomes of regorafenib was analyzed. RESULTS: In patients who were receiving regorafenib 40-160 mg/day, the Ctrough values of regorafenib, M2, and M5 were 318-9467, 34-3594, and 38-3796 ng/mL, respectively. The difference in the values was significant. Although the specific factors influencing this difference were not elucidated, the Ctrough of regorafenib was extremely lower in some patients, even though the drug was administered at a standard dose, which may explain the lower response rate. Moreover, the Ctrough value of M5 was significantly correlated to the incidence of skin toxicities, which is the most frequent cause of dose modification. CONCLUSIONS: The use of regorafenib may not be suitable in patients with a low Ctrough value. To prevent skin toxicities, the Ctrough value of M5 should be monitored.

3.
World J Surg Oncol ; 17(1): 197, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771590

RESUMO

BACKGROUND: In Japan, the majority of gastrointestinal tract neuroendocrine tumors (NETs) have been reported to originate from the rectum, and appendiceal NETs are relatively rare. Preoperative diagnosis is very difficult and it is diagnosed after appendectomy. Pediatric appendiceal NET is a disease with a good prognosis. However, in rare cases, lymph node metastasis could occur and additional resection is required. CASE PRESENTATION: A 10-year-old boy complained of right lower quadrant abdominal pain and underwent an appendectomy under a diagnosis of acute appendicitis in previous hospital. The final diagnosis was appendiceal NET, so he was referred to our department for additional resection. The tumor was found in the base of the appendix and invasively reached the subserosal layer with obvious vascular invasion. His Ki-67 index was 1 to 2%, so we classified it as appendiceal NET G1 according to the WHO 2015 classification. We considered the possibility of a tumor remnant or lymph node metastasis, so we performed single-incision laparoscopy with D3 lymph node dissection. The pathological diagnosis revealed no tumor remnant but metastasis to one lymph node. He was discharged on the 9th postoperative day. There has been no recurrence at 3 years and 7 months after surgery. CONCLUSION: When the tumor size is 10-20 mm, the frequency of lymph node metastasis in some reports is variable, and there is no consensus yet on the indications for additional resection. However, there are definitely a certain number of cases with lymph node metastasis that require additional resection. In the present patient, long-term survival can be obtained by additional resection. At present, factors such as the presence of vascular or lymph node invasion and the malignancy grade and tumor's location must be considered on a case-by-case basis. Although the incidence rate of appendiceal NET is rare, the diagnosis can be made only during postoperative pathological examination; thus, reliable histopathological examination is required.

4.
Oncologist ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748337

RESUMO

OBJECTIVE: TAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC. PATIENTS AND METHODS: We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m2, twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis. RESULTS: Data from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups. CONCLUSION: Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies. IMPLICATIONS FOR PRACTICE: Combining bevacizumab (Bmab) with TAS-102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC.

5.
World J Surg Oncol ; 17(1): 178, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677643

RESUMO

BACKGROUND: In recent years, laparoscopic surgery has been widely used for rectal cancer. In laparoscopic rectal surgery, a double-stapling technique (DST) anastomosis using a stapling device is considered a relatively difficult procedure. Postoperative anastomotic leakage (AL) is a major complication related to patients' quality of life and prognosis. METHODS: This study was a retrospective, single-institution study of 101 rectal cancer patients who underwent laparoscopic low anterior resection (LAR) with DST anastomosis (excluding simultaneous resection of other organs and construction of protective diverting stoma) between February 2008 and November 2017 at the Gifu University Graduate School of Medicine. This study aimed to identify risk and early predictive factors of AL. RESULTS: Among 101 patients, symptomatic AL occurred in 13 patients (12.9%), of whom 10 were male and 3 were female. Their median BMI was 22.7 kg/m2 (range, 17.9-26.4 kg/m2). Among the pre- and intraoperative factors, AL was significantly associated with tumor location (lower rectum), distance from the anal verge (< 6 cm), intraoperative blood loss (≥ 50 ml), and the number of linear staples (≥ 2) in univariate analysis. In multivariate analysis, only intraoperative blood loss (≥ 50 ml, odds ratio [OR] 4.59; 95% confidence interval [CI] 1.04-19.52; p = 0.045) was identified as an independent risk factor for AL. Among the postoperative factors, AL was significantly associated with tachycardia-POD1 (≥ 100 bpm), CRP-POD3 (≥ 15 mg/dl), fever on postoperative day (fever-POD) 3 (≥ 38 °C), and first defecation day after surgery (< POD3) in univariate analysis. In multivariate analysis, fever-POD3 (≥ 38 °C, OR 30.97; 95% CI 4.68-311.22; p = 0.0003) and first defecation day after surgery (< POD3, OR 5.82; 95% CI 1.34-31.30; p = 0.019) were identified as early predictive factors for AL. CONCLUSION: In this study, intraoperative blood loss was an indicator of difficulty in a transection and anastomosing procedure, and fever-POD3 and early first defecation day after surgery were independent early predictive factors for AL. Careful surgery using an appropriate technique and standardized procedures with minimal bleeding and careful postoperative management paying attention to fever and defecation may prevent the onset and severity of AL.

6.
Mol Clin Oncol ; 11(4): 390-396, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31475067

RESUMO

The combination regimen of TAS-102, a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, with bevacizumab (C-TASK FORCE), a selective monoclonal antibody inhibitor of vascular endothelial growth factor-A, as salvage-line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness. The aim of the present study was to evaluate the prognostic accuracy of the modified Glasgow Prognostic Score (mGPS) in patients receiving TAS-102 plus bevacizumab. The study included 17 patients (12 men and 5 women, mean age 60.4±13.4 years) with unresectable mCRC who were confirmed to have wild-type or mutant RAS genes. The patients received salvage-line treatment with TAS-102 plus bevacizumab at the Surgical Oncology Department of Gifu University School of Medicine between March 2016 and August 2018. The study population was heavily pretreated; the majority of the patients (71%) had received ≥4 prior regimens and, in addition to fluoropyrimidine, irinotecan and oxaliplatin, all had received bevacizumab (100%) and either cetuximab or panitumumab (47%). The RAS status was wild-type in 9 (53%) and mutant in 8 (47%) patients. The primary tumor locations included the right-sided colon in 5 patients (29%; cecum in 2 and transverse colon in 3 cases) and left-sided colorectum in 12 patients [71%; sigmoid colon in 4, rectosigmoid (Rs) in 4, and rectum above/below the peritoneal reflection (Ra/b) in 4 cases]. Metastatic sites included the liver in 15 (88%), lung in 13 (76%), lymph nodes in 7 (41%), and peritoneal dissemination in 5 (24%) patients. The number of metastatic sites was 1 in 3 (18%) and >2 in 14 (82%) patients. Their first staging imaging scans (after 2 cycles of therapy) were available for review in all 17 patients. At first evaluation, 5 (29%) patients had progressive disease (PD), 12 (71%) had stable disease, and none had a partial response to TAS-102 plus bevacizumab. The median overall survival (OS) of 14.1 months and progression-free survival (PFS) of 6.8 months were comparable to the 11.2 and 5.6 months, respectively, in the C-TASK FORCE study. Upon considering three groups, namely mGPS 0, mGPS 1 and mGPS 2, the median PFS times were significantly different (mGPS 0 vs. mGPS 2, P=0.02; and mGPS 1 vs. mGPS 2, P=0.06). The median PFS times in the mGPS 0, 1 and 2 groups were 12.1, 4.8 and 2.3 months, respectively. Median OS was also significantly different (mGPS 0 vs. mGPS 2, P=0.01; and mGPS 1 vs. mGPS 2, P=0.04). The median OS times in the mGPS 0, 1 and 2 groups were 14.0, not reached, and 2 months, respectively. The present study demonstrated the efficacy and safety of the TAS-102 plus bevacizumab combination as salvage-line treatment. This combination therapy (the TAS-102 plus bevacizumab) has obtained valid results with PFS OS as well as C-TASK.FORCE study. The results of the present study also confirmed the prognostic accuracy of mGPS in salvage-line treatment of patients with mCRC.

7.
J Clin Med ; 8(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443371

RESUMO

Cancer cells can survive and grow via angiogenesis. An alternative but controversial theory is cancer cells may grow via vasculogenic mimicry (VM), in which the cancer cells themselves construct vessel-like channels that are considered a leading cause of drug resistance. The dynamic functions of the glycocalyx (GCX), a meshwork composed of proteoglycans and glycoproteins that surrounds cell membranes, have been observed in endothelial cells within tumors. However, the actual structural shape formed by the GCX in human patients remains unclear. Here, we visualized the three-dimensional (3D) network structure constructed by bulky GCX in human colorectal cancer (CRC) patients using scanning electron microscopy with lanthanum nitrate staining. The network structure extended throughout the cancer cell nest, opening into capillaries, with a tunnel channel that exhibited a net- and spongy-like ultrastructure. The expression of endothelial and cancer-specific GCX-binding lectins was dramatically increased in the interstitial spaces between cancer cells. Even accounting for the presence of artifacts resulting from sample preparation methods, the intercellular tunnels appeared to be coated with the bulky GCX. Further, this 3D network structure was also observed in the tumors of ApcMin/+ mice. In conclusion, the bulky GCX modifies the network structure of CRCs in human and mice.

8.
Mol Clin Oncol ; 11(2): 189-191, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31281655

RESUMO

Development of diabetic ketoacidosis (DKA) caused by fulminant type 1 diabetes (FT1D) during administration of uracil-tegafur (UFT) with leucovorin (LV) as adjuvant chemotherapy is extremely rare. Here, we report a case of DKA caused by FT1D during administration of UFT with LV as adjuvant chemotherapy for colon cancer. A woman in her 60s was transferred to the emergency medical center of our hospital with complaints of impaired consciousness and vomiting. She had undergone left hemicolectomy and D3 lymph node dissection for transverse colon cancer 8 months earlier. She was provided UFT with LV as adjuvant chemotherapy. Laboratory analysis revealed hyperglycemia, high anion gap metabolic acidosis and urinary ketones. She was diagnosed with DKA and was started on intravenous infusion of fluid and continuous subcutaneous insulin injections. Following admission, she was examined and diagnosed with FT1D. The present case describes an extremely rare case of DKA caused by FT1D during adjuvant chemotherapy with UFT + LV for colon cancer.

9.
Asian J Endosc Surg ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332934

RESUMO

An intractable fistula caused by idiopathic esophageal rupture is a rare but severe condition. In the present case, a 69-year-old man had been treated conservatively at another hospital for esophageal rupture but had developed an abscess in the left thoracic cavity due to an intractable fistula at the rupture site. He was referred to our hospital for treatment 19 months after the esophageal rupture. On admission, the intractable fistula was found to be continuous with an abscess in the left thoracic cavity. Preoperative continuous enteral nutrition was administered to improve the patient's nutritional status, and drainage was performed to reduce the size of the abscess. Then, to minimize the invasion of the intractable fistula, thoracoscopic subtotal esophagectomy was performed via a right thoracic cavity approach 20 months after the esophageal rupture. Preoperative management and thoracoscopic surgery via an opposite chest cavity approach was found to be safe and feasible for the intractable fistula caused by idiopathic esophageal rupture.

10.
Med Oncol ; 36(7): 63, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161433

RESUMO

Irinotecan is effective for the treatment of metastatic colorectal cancer (mCRC) and advanced pancreatic cancer (aPC). However, these treatments are often limited due to the incidence of severe neutropenia. We identified risk factors for severe neutropenia in patients with mCRC or aPC, receiving irinotecan-based chemotherapy regimens. The study selected 104 patients (mCRC: 53 and aPC: 51) who received irinotecan-based chemotherapy between January 2014 and May 2018 and who were included in the present study. The initial dose of irinotecan was 150 mg/m2 in all patients, and patients with a lower initial dose of irinotecan were excluded. Severe neutropenia (grade ≥ 3) occurred in 56 patients (53.8%). Multivariable Cox proportional hazards analysis indicated that modified FOLFIRINOX (mFOLFIRINOX) and serum total bilirubin (T-Bil) were significant risk factors for severe neutropenia. Moreover, with receiver-operating characteristic (ROC) curve analysis, the cutoff for T-Bil was found to be 0.7 mg/dL. Among patients treated with mFOLFIRINOX therapy, the incidence of severe neutropenia was significantly higher in patients with high level of T-Bil (> 0.7 mg/dL) than in those without it (93.8% vs 55.0%, P = 0.006). A chemotherapy regimen (modified FOLFIRINOX therapy) and T-Bil > 0.7 mg/dL were significant risk factors for severe neutropenia in patients receiving 150 mg/m2 irinotecan.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bilirrubina/sangue , Irinotecano/efeitos adversos , Neutropenia/sangue , Neutropenia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Incidência , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
11.
Anticancer Res ; 39(5): 2615-2625, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092460

RESUMO

BACKGROUND/AIM: This study aimed to assess whether low-molecular-weight heparin (LMWH) is effective and safe in preventing postoperative venous thromboembolism (VTE) in patients undergoing esophageal cancer surgery. PATIENTS AND METHODS: In this single-institution, prospective, randomized trial, 73 patients with esophageal cancer undergoing esophagectomy were randomly divided into the enoxaparin group (E group) and intermittent pneumatic compression group (I group). The primary endpoint was efficacy of enoxaparin, and secondary endpoints were evidence of bleeding and serum anti-Xa activity in the E group. RESULTS: The E group comprised 42 patients and the I group comprised 31 patients. Deep vein thrombosis was observed in 0 (0%) patients in the E group and 7 (22.6%) patients in the I group (p=0.002). Soluble fibrin monomer complex was significantly lower in the E versus I group on day 8 (p<0.001). D-dimer was significantly lower in the E versus I group on days 2, 8, and 15 (p=0.008, p<0.001, p<0.001, respectively). CONCLUSION: VTE was significantly reduced by using enoxaparin.


Assuntos
Enoxaparina/administração & dosagem , Neoplasias Esofágicas/complicações , Esofagectomia/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Idoso , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/patologia , Heparina de Baixo Peso Molecular , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Tromboembolia Venosa/etiologia , Trombose Venosa/diagnóstico , Trombose Venosa/patologia , Trombose Venosa/prevenção & controle
12.
Int J Mol Sci ; 20(7)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959742

RESUMO

Gastric cancer (GC) is one of the most common cancers worldwide. In the clinical setting, the identification of HER2 overexpression in GC was a significant finding, as trastuzumab, an anti-HER2 drug, provides a survival advantage to HER2-positive GC patients. In HER2-postive GC, the dysregulation of PI3K/AKT and MAPK/ERK signaling pathways has been reported, and inhibition of these pathways is an important therapeutic strategy. MiR-143 is known to act as a tumor suppressor in several cancers, such as bladder cancer, breast cancer, colorectal cancer, and gastric cancer. In the current study, we developed a novel chemically-modified miR-143 and explored the functions of this synthetic miR-143 (syn-miR-143) in HER2-positive gastric cancer. The expression level of miR-143 was down-regulated in GC cell lines, including HER2-positive GC cell lines, MKN7, and KATO-III. The ectopic expression of miR-143 in those cell lines suppressed cell growth through systemic silencing of KRAS and its effector signaling molecules, AKT and ERK. Furthermore, syn-miR-143 indirectly down-regulated the expression of HER2, an upstream molecule of KRAS, through silencing DEAD/H-box RNA helicase 6 (DDX6), RNA helicase, which enhanced HER2 protein expression at the translational step in HER2-positive GC cells. These findings suggested that syn-miR-143 acted as a tumor suppressor through the impairment of KRAS networks including the DDX6.


Assuntos
RNA Helicases DEAD-box/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Animais , Antagomirs/metabolismo , Apoptose/genética , Sequência de Bases , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos Nus , MicroRNAs/genética , Modelos Biológicos , Transdução de Sinais , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Mol Clin Oncol ; 10(6): 571-574, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31031973

RESUMO

The combination of cetuximab (CTX) and chemotherapy, such as FOLFOX or FOLFIRI, is currently the standard treatment for metastatic colorectal cancer (mCRC). Zoledronic acid (ZOL) is used in patients with bone metastasis. We herein report our experience with the case of a 58-year-old male patient with metastatic rectal cancer who was treated with ZOL + CTX as third-line therapy, and in whom this combination appeared to be effective. Although the patient developed bone metastasis and cardiac tamponade due to the recurrence of rectal cancer, he survived for approximately 10 months after the initiation of ZOL and CTX treatment.

14.
Cancer Chemother Pharmacol ; 83(1): 123-129, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30377777

RESUMO

PURPOSE: Irinotecan is effective for metastatic colorectal cancer (mCRC). SN-38 is an active metabolite of irinotecan, which is formed by carboxylesterase and inactivated by UDP-glucuronyltransferase (UGT) 1A1. The UGT enzyme activity is reduced in patients with homozygous mutation in UGT1A1 genes (*6/*6, *28/*28 and *6/*28); thus dose reduction is required for prevention of severe adverse events associated with irinotecan. The present study was designed to investigate the relationship between UGT1A1 polymorphisms and the incidence of adverse events or the therapeutic effect in mCRC patients who received irinotecan. METHODS: Sixty-three mCRC patients who received irinotecan during January 2014 and May 2018 were the subjects of this study. The incidence of adverse events, including diarrhea and neutropenia, and the therapeutic effect of irinotecan were compared among homozygous group, heterozygous group and wild-type group. The initial dose of irinotecan was 150 mg/m2 in the heterozygous group and wild-type group, while the dose was reduced by 20% (120 mg/m2) in the homozygous group. RESULTS: The UGT1A1 polymorphisms occurred in 15.9%, 33.3%, and 50.8% for homozygous group, heterozygous group, and wild-type group, respectively. The average dose of irinotecan during overall cycles was not significantly different among three groups, despite the reduction of initial dose in homozygous group. There were no significant differences in the incidence rates of adverse events, tumor response, or time to treatment failure among three groups. CONCLUSION: The present study demonstrated that dose reduction by 20% ensured safety and efficacy of irinotecan in mCRC patients with homozygous mutation in UGT1A1 genes.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucuronosiltransferase/genética , Irinotecano/administração & dosagem , Polimorfismo Genético , Inibidores da Topoisomerase I/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Genótipo , Homozigoto , Humanos , Irinotecano/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Inibidores da Topoisomerase I/sangue
15.
Cancer Chemother Pharmacol ; 83(3): 393-398, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30564875

RESUMO

BACKGROUND/AIM: Cholinergic syndrome frequently occurs within the first 24 h after irinotecan injection. We evaluated the prophylactic effect of scopolamine butylbromide on irinotecan-related cholinergic syndrome. PATIENTS AND METHODS: Fifty-nine patients who received irinotecan-based regimens at our outpatient chemotherapy clinic between April 2013 and May 2014 were enrolled. Patients who developed irinotecan-related cholinergic syndrome were prophylactically administered scopolamine butylbromide at the next scheduled treatment. Risk factors for irinotecan-related cholinergic syndrome were determined using logistic regression analysis. RESULTS: Irinotecan-related cholinergic syndrome occurred in 50.8% of patients. Scopolamine butylbromide administration significantly reduced the incidence to 3.4% (P < 0.01). The irinotecan dose (≥ 150 mg/m2) was the only risk factor associated with irinotecan-related cholinergic syndrome. The incidence of cholinergic syndrome in patients with this risk factor was 75%. CONCLUSION: Scopolamine butylbromide was effective in preventing irinotecan-related cholinergic syndrome. It is recommended for patients receiving ≥ 150 mg/m2 irinotecan who may develop cholinergic syndrome at high frequency.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brometo de Butilescopolamônio/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Irinotecano/efeitos adversos , Antagonistas Muscarínicos/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Incidência , Irinotecano/administração & dosagem , Japão , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Parassimpático/efeitos dos fármacos , Fatores de Risco , Síndrome
16.
Mol Clin Oncol ; 9(6): 587-591, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30546885

RESUMO

Pathological complete response is achievable with mFOLFOX6 plus cetuximab therapy for unresectable colorectal cancer with multiple paraaortic lymph node metastases (mCRC) despite right-sided colonic origin. A 62-year-old woman with synchronous paraaortic lymph node metastases of transverse colon cancer was treated with mFOLFOX6 plus cetuximab as first-line therapy. The tumor size was markedly decreased following 6 courses of chemotherapy, and all lymph node metastases had disappeared. The patient then underwent conventional right hemicolectomy with D3 lymph node dissection plus sampling excision of the paraaortic lymph nodes. The pathological diagnosis was a complete response. The patient is currently alive 5 years after surgery with no signs of recurrence. The present study reported the apparent effectiveness of conversion therapy (surgery) with combination treatment with mFOLFOX6 plus cetuximab and radical surgery. We hypothesized that patients with different types of mCRC of right-sided colon origin may be effectively treated with anti-EGFR monoclonal antibodies.

17.
Gan To Kagaku Ryoho ; 45(10): 1546-1548, 2018 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-30382073

RESUMO

Immunological checkpoint inhibitors have effects on various advancedcancers. Nivolumab was approvedfor advanced gastric cancer after third-line treatment in 2017. In our hospital, 10 patients were treatedwith nivolumab from October 2017 to March 2018. Thus, we retrospectively examinedthe clinical background, treatment outcomes, andad verse events of those patients. The median age was 70 years; male-to-female ratio was 6:4; recurrence sites were peritoneal dissemination, liver, lymph nodes, brain, ovaries, and bone(8, 2, 2, 1, 1, and1 , respectively); andtreatment lines were third, fourth, andfifth(in 6, 3, and1 patients, respectively). The minimum number of cycles was 1 course, while the maximum was 11 courses. The best tumor response evaluation was SD, andthe adverse event was an itching sensation in only one patient. It was suggestedthat long-term SD couldbe maintainedwhen the nivolumab treatment was initiatedin a patient with goodPS. In the future, biomarker analysis is expectedto identify effective cases.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
18.
Anticancer Res ; 38(11): 6367-6373, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396959

RESUMO

BACKGROUND/AIM: Dysgeusia is one of the adverse events frequently affecting patients undergoing cancer chemotherapy. Dysgeusia-induced anorexia could decrease patient's quality of life. The present study was designed to determine whether the zinc-containing compound polaprezinc improves chemotherapy-induced dysgeusia. PATIENTS AND METHODS: The incidence of grade 2 dysgeusia was assessed in 634 patients receiving cancer chemotherapy in outpatient settings during January 2013 and June 2017. Polaprezinc was administered to patients showing grade 2 dysgeusia and the effect was compared with that in patients subjected to follow-up observation. RESULTS: Grade 2 dysgeusia appeared in 80 patients (12.6%), in whom pancreatic cancer and treatment with fluoropyrimidines were significant risks for dysgeusia. Polaprezinc, when administered to patients with grade 2 dysgeusia, significantly shortened the duration of dysgeusia compared with that in the follow-up observation group. Subgroup analysis indicated that polaprezinc was less effective in patients with pancreatic cancer, those receiving gemcitabine, or those whose age was 65 year-old and over. CONCLUSION: Chemotherapy-induced dysgeusia occurred with high frequency in patients with pancreatic cancer or in those receiving fluoropyrimidines. Polaprezinc was highly effective in improving the symptom of dysgeusia, except for patients with pancreatic cancer, those receiving gemcitabine and the elderly.


Assuntos
Antineoplásicos/efeitos adversos , Carnosina/análogos & derivados , Disgeusia/tratamento farmacológico , Compostos Organometálicos/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Administração Oral , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carnosina/administração & dosagem , Carnosina/uso terapêutico , Tratamento Farmacológico , Disgeusia/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Pacientes Ambulatoriais , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem , Compostos de Zinco/administração & dosagem , Compostos de Zinco/uso terapêutico
20.
Mol Clin Oncol ; 9(3): 305-309, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30155253

RESUMO

We herein report a case of local recurrence of T1a rectal cancer following radical endoscopic mucosal resection (EMR). A 63-year-old man underwent EMR for a 0-IIa lesion of the Ra portion of the rectum. The findings on pathological examination were tub1, T1a (SM1, 420 µm), ly0 and v0, and the EMR had been considered a transitional procedure. Colonoscopy performed 26 months after EMR revealed a submucosal tumor (SMT) near the EMR scar in the left wall of the Ra portion of the rectum. An abdominal enhanced computed tomography scan revealed infiltration of the thickness of the wall with limited extramural extension, and a lymph node 10 mm in diameter. Endoscopic ultrasound-guided fine-needle aspiration also indicated a SMT on the left side of the Ra portion of the rectum that extended from the submucosal layer to beyond the serosal layer, and a lymph node sized 17×11 mm to the left of the Ra portion near the oral side 2 cm from the SMT. The pathological findings confirmed the SMT to be an adenocarcinoma with a metastatic lymph node. Local and lymph node recurrence of rectal cancer following radical EMR was diagnosed, and laparoscopic ultra-low anterior resection, D3 lymph node dissection and a diverting ileostomy were performed. The pathological findings of the excised specimen were T3 (A/SS), ly0, v3, PN1b, pPM0, pDM0, pRM0 (100 µm) and pN0 (0/15). XELOX therapy was administered for 6 months postoperatively as adjuvant chemotherapy, and there has been no recurrence during the first 12 months of follow-up.

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