Safety and efficacy of adjuvant chemotherapy with oxaliplatin and S-1 for patients with locally advanced gastric cancer after D2 lymph nodes dissection / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.

Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer / 中华胃肠外科杂志

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

Efficacy of S-1 in Advanced Non-small Cell Lung Cancer Patients Treated with More Than Two Lines of Chemotherapy / 中国肺癌杂志

BACKGROUND@#There is no standard treatment for advanced non-small cell lung cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third generation of fluorouracil derivate with well safety and low toxicity, presented some efficacy in lung cancer treatment. The aim of this study is to explore the efficacy of S-1 for advanced NSCLC patients treated with two or more prior chemotherapy regimens.@*METHODS@#We performed a retrospective analysis of 105 NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the third or more line of treatment in our hospital from January 2014 to April 2017. S-1 was administrated orally twice daily for 2 weeks, followed by one week of rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d; 1.25 m2-1.5 m2, 100 mg/d; ≥1.5 m2, 120 mg/d), platinum or the third-generation chemotherapy drugs could be combinedly used. Clinical response was assigned every cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS).@*RESULTS@#42 patients received S-1 monotherapy, the other 63 patients received combined regimens, the median treatment line was 4 (3-11) and the median treatment cycle was 2 (1-14). No complete response (CR) were observed, there were 4 patients with partial response (PR), 34 patients with stable disease (SD) and 67 patients with progressive disease (PD), the objective response rate (ORR) was 3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months (0.67 months-10.83 months), no difference between monotherapy and combined group (DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40 months vs 1.93 months , P=0.042).@*CONCLUSIONS@#S-1 presented some activity in advanced NSCLC treated with more than two lines of treatment. The addition of other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for heavily-treated patients.

A Case of Achieving Complete Remission with Combination of Sorafenib and Tegafur in Patients with Hepatocellular Carcinoma with Progression of Disease after Sorafenib Therapy

Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under 3 months is far from clinical satisfactory and most patients experience disease progression within 6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment failure of sorafenib was not established and there were no clear guidelines for salvage treatment modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent can be relatively effective and safe strategy that achieves promising rates of local and systemic control in advanced HCC patients. Based on above suggestions, we herein offer our experience of a case achieved complete remission by combination therapy of sorafenib and tegafur in the patient with progressed disease after sorafenib therapy.

Comparison of the efficacy and safety of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin chemotherapy regimens in the treatment of advanced gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients.</p><p><b>METHODS</b>A total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed.</p><p><b>RESULTS</b>The objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients.</p><p><b>CONCLUSIONS</b>Both CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.</p>

Clinical Observation of Bevacizumab Combined with S-1 in the Treatment of Pretreated Advanced Esophageal Carcinoma / 中国医学科学杂志(英文版)

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m·d on day 1-14, 21 days as a cycle of treatment and repeated until either pro- gressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response (CR+PR) rate was 22.4% (17/76) and disease control (CR+PR+SD) rate was 61.8% (47/76) respectively. The median follow-up time was 20 months (range from 9 to 44 months). The median progression-free survival (PFS) was 4.9 months (95% CI 4.4-5.5) and the median overall survival (OS) was 8.1 months (95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months (95% CI 3.3 to 6.3) and 8.5 months (95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence (median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis (median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia (84.2%), grade I-II hand and foot syndrome (51.3%), grade I-II nausea (48.7%), mild epistaxis (30.1%) and mild vomiting (14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient (1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.

Relationship between BH3 mimetic S1 and expression of BCL-2 family members in acute myeloid leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to investigate the molecular biomarkers of apoptosis induced by BH3 mimetic S1 in human primary AML cells.</p><p><b>METHODS</b>Mononuclear cells were isolated from 27 newly diagnosed AML samples. Apoptosis was analyzed by flow cytometry. IC(50) value of S1 on these samples was determined by XTT assay. The expression level of BCL-2 family members and phosphorylated BCL-2 were assessed by Western blot with subsequent semi-quantitatively densitometric analysis. XTT assay was performed to determine the cell viability of the combined use of S1 and MEK/ERK inhibitor PD98059. The interactions between BCL-2 and pro-apoptosis proteins were tested by co-immunoprecipitation.</p><p><b>RESULTS</b>The flow-cytometry detection showed that S1 induced the apoptosis of primary AML cells. Based on the responses, 27 primary samples could be classified into three groups: (1) a sensitive group (12 of 27 cases) with IC(50)<14 µmol/L, (2) an intermediate group (8 of 27 cases) with IC(50) of 14-30 µmol/L and (3) a resistant group (7 of 27 cases) with IC(50)>30 µmol/L. The ratio of pBCL-2/(BCL-2+MCL-1) showed a good linear correlation with the IC(50) values. (R(2) = 0.71, P < 0.0001). PD98059 suppressed BCL-2 phosphorylation. When PD98059 suppressed BCL-2 phosphorylation, the apoptotic rate of drug-resistant cells induced by S1 increased from 9.8% to 64.5% (combination index, CI = 0.4), accompanied by more dissociation of BCL-2 heterodimers.</p><p><b>CONCLUSION</b>The combination of S1 with PD98059 decrease pBCL-2 level of AML patients and inhibits of the anti-apoptotic function of BCL-2 through enhancing the dissociation of BCL-2 heterodimers.</p>

Safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer.</p><p><b>METHODS</b>A retrospective analysis of the clinical data of 49 patients with advanced pancreatic cancer, who did not receive radiotherapy and chemotherapy, were divided into two groups: the study group (25 cases), and control group (24 cases). Patients in the study group received gemcitabine 1 000 mg/m² via intravenous drip at the first and 8th days, and received S-1 80 mg/m², morning and evening (twice a day) for the first 14 days, and 21 days as a treatment cycle of chemotherapy.The control group was given GEMOX regimen: Gemcitabine 1 000 mg/m² via intravenous drip at the first and 8 days, and oxaliplatin 130 mg/m² via intravenous drip at the first day, and 21 d for a treatment cycle of chemotherapy. The efficacy and adverse reactions in patients of the study and control groups were observed and compared.</p><p><b>RESULTS</b>The efficiency of the study group was 32.0% and disease control rate was 72.0%. The efficiency of the control group was 25.0% and disease control rate was 58.3%. The differences between the two groups were statistically not significant (P > 0.05 for all). The clinical benefit rate in the study group and control group were 80.0% and 50.0%, respectively, showing a significant difference (P < 0.05). The median survival time was 9.7 months in patients of the study group and 9.0 months in the control group, with a significant difference (P < 0.05). The drug toxicity was well tolerated in both groups, and no chemotherapy-related death occurred. The major adverse reactions were myelosuppression and digestive tract reactions, and the adverse reactions in the study group were lower than those in the control group.</p><p><b>CONCLUSIONS</b>Gemcitabine combined with S-1 is effective and safe in the treatment of advanced pancreatic cancer, with less side effects, and can be tolerated by the patients.</p>

Volume-reserving Surgery after Photodynamic Therapy for Biliary Papillomatosis: A Case Report / 대한소화기학회지

Biliary papillomatosis is rare, and its pathogenic mechanisms are not yet clear. Because of its high risk for malignancy transformation, surgical resection is regarded as a standard treatment. Photodynamic therapy (PDT) has been used by the intravenous administration of hematoporphyrin derivative followed by laser exposure. A photochemical process causes disturbance of the microvascular structure and degradation of membrane. Cholangitis is a major complication after PDT. A healthy 56-year-old man was diagnosed with biliary papillomatosis involving the common hepatic duct, both proximal intrahepatic bile ducts (IHD), and the right posterior IHD. After biliary decompression by endoscopic nasobiliary drainage, PDT was performed to avoid extensive liver resection and recurrence using endoscopic retrograde cholangiographic guidance. After portal vein embolization, the patient underwent extended right hemihepatectomy. Following administration of chemoradiation therapy with tegafur-uracil and 45 Gy due to local recurrence at postoperative 13 months, there was no local recurrence or distant metastases. This is the first case report on PDT for biliary papillomatosis in Korea. Preoperative PDT is beneficial for reducing the lesion in diffuse or multifocal biliary papillomatosis and may lead to curative and volume reserving surgery. Thus, PDT could improve the quality of life and prolong life expectation for biliary papillomatosis patients.

High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer / 부인종양

OBJECTIVE: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. METHODS: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. RESULTS: In the UFT group, 103 patients (63.6%) received UFT for > or =90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). CONCLUSION: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.

Efeito da revascularização renal sobre a evolução da disfunção renal na nefropatia isquêmica aterosclerótica / Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy

A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.

Comportamentos e práticas sexuais de homens que fazem sexo com homens / Sexual behaviors and practices of men who have sex with men / Conductas y prácticas sexuales de los hombres que tienen sexo con hombres

Objetivou-se identificar comportamentos e práticas sexuais de homens que fazem sexo com homens no contexto da vulnerabilidade ao HIV/AIDS. Estudo transversal, exploratório descritivo. Foi realizado em um local de sociabilidade gay de Fortaleza, no Estado do Ceará, entre novembro de 2010 e março de 2011, por meio de entrevista com 189 homens que fazem sexo com homens. Encontrou-se uma amostra composta, majoritariamente, por jovens, solteiros e com alto nível educacional. A história sexual demonstrou o início precoce da vida sexual, com prevalência elevada de relação sexual com parceira do sexo oposto. Houve alta frequência de testagem para o HIV. As práticas sexuais revelaram prevalência superior da realização de sexo oral e anal, bem como altos níveis de proteção no sexo anal, apesar de baixa no sexo oral. Constatou-se uma maior incorporação das práticas de prevenção em relação ao panorama nacional do início da epidemia.

The objective was to identify behaviors and sexual practices of men who have sexual relations with other men in the context of vulnerability to HIV/AIDS. This was a cross-sectional, exploratory and descriptive study. It was carried out in a gay sociability place in Fortaleza, Ceará, Brazil, between November 2010 and March 2011, through interviews with 189 men who have sex with men. The ethical aspects were respected. We found a sample consisting mostly by young, single, and highly educated men. The sexual history demonstrated the early onset of sexual activity, with a high prevalence of sexual intercourse with a partner of the opposite sex. There was also a high prevalence of HIV testing. Sexual practices revealed high prevalence of performing oral and anal sex, as well as high levels of protection in anal sex, despite the low protection in oral sex. A greater incorporation of prevention practices was found compared to the national scene in the beginning of the disease outbreak.

El objetivo fue identificar los comportamientos y las prácticas sexuales de los hombres que tienen sexo con hombres en el contexto de la vulnerabilidad al VIH/SIDA. Fue un estudio transversal, descriptivo y exploratorio. Se celebró en una sociabilidad local gay de Fortaleza, Ceará, Brasil, entre noviembre de 2010 y marzo de 2011, a través de entrevistas con 189 hombres que tienen sexo con hombres. Se encontró una muestra compuesta en su mayoría por jóvenes, solteros y con alto nivel de educación. La historia sexual demostró el inicio temprano de la actividad sexual, la alta prevalencia de relaciones sexuales con una pareja del sexo opuesto. Hubo alta prevalencia de la prueba del VIH. Las prácticas sexuales revelaron una alta prevalencia de realizar sexo oral y anal, así como altos niveles de protección en el sexo anal, a pesar de la baja protección en el sexo oral. Se encontró una mayor incorporación de las prácticas de prevención en relación con la escena nacional en el inicio de la epidemia.

Discomfort and unease of the subject in the interpretation movement of a Tuberculosis questionnaire / O desconforto e inquietação do sujeito em seu movimento de interpretação de um questionário sobre a tuberculose / Malestar e inquietud del sujeto en su movimiento de interpretación de un cuestionario sobre la Tuberculosis

OBJECTIVE: to propose a discussion about traces of the derivation of meanings, the subjects' discomfort and resistance when they are called upon to signify a questionnaire on the transfer of the Directly Observed Treatment of Tuberculosis policy, in order to reveal the limitations of closed questionnaires in the subject's interpretation process. METHOD: health professionals from a Primary Health Care Unit in Porto Alegre/RS were interviewed and some excerpts from the interviews were investigated in the light of French Discourse Analysis. RESULTS: resistance, discomfort, slips, silencing and the derivation of meanings were observed in the subjects' interpretation. CONCLUSION: the interpretation process has multiple meanings and varies from subject to subject. The questionnaire, as a prototype of the logically stabilized universe, fails when the purpose is to control the interpretation. Its isolated use in health research can entail inexactness or incompleteness of the collected data. Therefore, its use associated with qualitative research techniques is ideal. .

OBJETIVO: propor uma discussão a respeito de vestígios da derivação de sentidos, do desconforto e resistência dos sujeitos, quando convocados a significar um questionário referente à transferência da política do tratamento diretamente observado da tuberculose, de modo a revelar as limitações de questionários fechados, quando se trata do processo interpretativo do sujeito. MÉTODO: profissionais de saúde de uma Unidade de Atenção Primária de Saúde de Porto Alegre, RS, foram entrevistados e alguns recortes das entrevistas examinados à luz da Análise de Discurso de linha francesa. RESULTADOS: observou-se a resistência, o incômodo, o deslizamento, o silenciamento e a derivação dos sentidos no ato de interpretação dos sujeitos. CONCLUSÃO: o processo de interpretação é polissêmico e varia de sujeito para sujeito. O questionário, enquanto um protótipo do universo logicamente estabilizado, falha quando o propósito é o de controlar a interpretação. O seu uso de forma isolada, em pesquisas em saúde, pode incorrer em inexatidão ou incompletude dos dados obtidos, sendo ideal a sua utilização associada a técnicas qualitativas de pesquisa. .

OBJETIVO: proponer una discusión respecto a vestigios de la derivación de sentidos, del malestar y resistencia de los sujetos cuando convocados a significar un cuestionario respecto a la trasferencia de la política del Tratamiento Directamente Observado de la Tuberculosis, de manera a revelar las limitaciones de cuestionarios cerrados cuando se trata del proceso interpretativo del sujeto. MÉTODO: profesionales de salud de una Unidad de Atención Primaria de Salud de Porto Alegre/RS fueron entrevistados y algunos recortes de las entrevistas examinados a la luz del Análisis de Discurso de línea Francesa. RESULTADOS: fueron observados la resistencia, la molestia, el deslizamiento, el silenciamiento y la derivación de los sentidos en el acto de interpretación de los sujetos. CONCLUSIÓN: el proceso de interpretación es polisémico y varia de sujeto a sujeto. El cuestionario como un prototipo del universo lógicamente estabilizado falla cuando el objetivo es el de controlar la interpretación. Su uso de forma aislada en investigaciones en salud puede llevar a datos inexactos o incompletos, siendo ideal su utilización asociada a técnicas cualitativas de investigación. .

Farmacogenómica del tratamiento de primera línea en el cáncer gástrico: avances en la identificación de los biomarcadores genómicos de respuesta clínica / Pharmacogenomics of the first-line treatment for gastric cancer: advances in the identification of genomic biomarkers for clinical response to chemotherapy

Debido a la inespecificidad de los síntomas, el cáncer gástrico (CG) es diagnosticado frecuentemente en etapas avanzadas, lo que da cuenta de los altos índices de mortalidad debido a esta neoplasia a nivel mundial. El esquema de tratamiento adyuvante o neoadyuvante en los países occidentales incluye el uso de fluoropirimidinas citotóxicas y compuestos de platino formadores de aductos en el ADN. La respuesta clínica al tratamiento con estos fármacos depende principalmente de la sensibilidad del tumor, la cual a su vez está condicionada por el nivel de expresión de los blancos terapéuticos y de las enzimas de reparación del ADN. Sumado a esto, algunos polimorfismos de línea germinal en genes asociados al metabolismo y a la respuesta a estos fármacos, han mostrado asociación con respuestas pobres y con el desarrollo de eventos adversos, incluso con resultados fatales. La identificación de biomarcadores genómicos, en la forma de polimorfismos genéticos o la expresión diferencial de genes específicos asociados a la respuesta quimioterapeútica ha sido motivo de intensa investigación como base para la aplicación de la farmacogenómica en el establecimiento de una terapia farmacológica racional y personalizada del CG. Sin embargo, ante la eventual aplicación de la farmacogenómica en el ámbito clínico, es necesario establecer el valor pronóstico real de dichos biomarcadores mediante los estudios de asociación genotipo-fenotipo, así como su prevalencia en el contexto de cada población de pacientes. Estos aspectos son indispensables al evaluar la relación costo-efectividad de la introducción de los productos de la medicina genómica predictiva en el tratamiento del CG.

Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.

Aprendizaje cooperativo para forjar vivienda saludable en Bogotá: estudio de caso / Cooperative learning for improving healthy housing conditions in Bogota: a case study

Objetivo Construir desde la comunidad una propuesta educativa orientada al auto empoderamiento para mejorar las condiciones sanitarias y de habitabilidad de la vivienda. Método Con un enfoque constructivista y con base en el programa "Gestores comunitarios del hábitat", se trabajó con quince familias residentes en el barrio Mochuelo Bajo de la Localidad de Ciudad Bolívar en Bogotá, Colombia, con el fin de que identificaran los aspectos sanitarios más relevantes para el mejoramiento de sus viviendas y propusieran la metodología y organización de la propuesta educativa. Resultados Se identificaron veinti ún indicadores epidemiológicos ligados a una vivienda insalubre, los cuales sirvieron como base para definir las problemáticas específicas y establecer la metodología para diseñar la propuesta educativa. Discusión El curso diseñado pretende fomentar la educación y las capacidades en salud de la comunidad con el fin de mejorar las condiciones de habitabilidad de las viviendas y lograr un entorno saludable del hábitat que les permita desarrollarse con bienestar y dignidad.

Objective This was a community-based effort at constructing an educational proposal orientated towards self-empowerment aimed at improving the target population's sanitary, housing and living conditions through cooperative learning. Methods A constructivist approach was adopted based on a programme called "Habitat community manger". The project involved working with fifteen families living in the Mochuelo Bajo barrio in Ciudad Bolívar in Bogotá, Colombia, for identifying the most relevant sanitary aspects for improving their homes and proposing a methodology and organisation for an educational proposal. Results Twenty-one poor housing-related epidemiological indicators were identified which formed the basis for defining specific problems and establishing a methodology for designing an educational proposal. Discussion The course which emerged from the cooperative learning experience was designed to promote the community's skills and education regarding health aimed at improving households' living conditions and ensuring a healthy environment which would allow them to develop an immediate habitat ensuring their own welfare and dignity.

A safety analysis in patients treated with oxaliplatin plus S-1 as adjuvant therapy for gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The combination of oxaliplatin and S-1 is effective in patients with advanced gastric cancer. The purpose of this study was to analyze the safety and compliance of this combination regimen as adjuvant chemotherapy in patients with gastric cancer.</p><p><b>METHODS</b>Clinical data of 71 patients with gastric cancer treated with oxaliplatin plus S-1 as adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) from Jan 1(st), 2010 to Jan 1(st), 2012 were retrospectively reviewed. The types and incidence rate of adverse events related to chemotherapy and the results of follow up of the patients were analyzed.</p><p><b>RESULTS</b>Among the 71 cases, 17 were treated with oxaliplatin biweekly, while 54 with oxaliplatin triweekly. The most common adverse events were neutropenia (n = 49, 69.0%), nausea/vomiting (n = 51, 71.8%), and anorexia (n = 49, 69.0%). The most frequent grade 3-4 toxicities were neutropenia (n = 13, 18.3%), thrombocytopenia (n = 10, 14.1%), anorexia (n = 5, 7.0%) and nausea/vomiting (n = 4, 5.6%). Seven (87.5%) of the 8 patients previously treated with neoadjuvant chemotherapy experienced thrombocytopenia in the postoperative adjuvant chemotherapy, and four (50%) of the 8 patients experienced grade 3-4 thrombocytopenia. The rates of grade 3-4 adverse events in patients aged 65-years or older were similar to that in younger patients.</p><p><b>CONCLUSIONS</b>The combination of oxaliplatin and S-1 used as adjuvant chemotherapy is well tolerated by patients with gastric cancer. Neutropenia, thrombocytopenia, nausea/vomiting and anorexia are the major treatment-related adverse events. Patients who received neoadjuvant chemotherapy do not well tolerate this regimen as postoperative adjuvant chemotherapy. This combination regimen has a manageable tolerability profile in adjuvant setting in patients ≥ 65 years old.</p>

A phase II prospective randomized controlled trial of weekly paclitaxel combined with S-1 or fluorouracil for advanced gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.</p><p><b>METHODS</b>Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.</p><p><b>RESULTS</b>Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.</p><p><b>CONCLUSIONS</b>Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.</p>

Pharmacokinetics of S-1 capsule in patients with advanced gastric cancer / 药学学报

The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.

Effecacy of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the local control rate, survival time and side effect of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma.</p><p><b>METHODS</b>Forty patients with postoperative recurrent rectal carcinoma received three-dimensional conformal radiation therapy, 1.8 - 2.0 Gy/once, 5 times every week and the total dose was 54 - 65 Gy. At the same time, the patients took Tegafur orally 40 mg/m(2) twice per day for consecutive 28 days, and one cycle lasted for 42 days. The chemotherapy was applied for 2 cycles after radiotherapy.</p><p><b>RESULTS</b>The total effective rate (CR + PR) was 70.0%, improvement rate was 90.0%, 1-year survival rate was 70.0%, and 1-year local control rate was 62.5%. There was only a little side effect.</p><p><b>CONCLUSIONS</b>Three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma have definite effect, with a high local control rate, and patients well tolerance the treatment without serious side effect. It can apparently improve the life quality of the patients.</p>

Efficacy and side effects of combination therapy of oxaliplatin and S-1 for colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the efficacy and side effects of the combination therapy of oxaliplatin and S-1 in treating postoperative colorectal cancer patients.</p><p><b>METHODS</b>54 postoperative colorectal cancer patients received the combination therapy of oxaliplatin and S-1 regimen, repeated every 3 weeks, and evaluate the efficacy after 3 cycles.</p><p><b>RESULTS</b>All of the 54 patients but 2 (changed the chemotherapy regimen after the first cycle because of economic reason) finished 6 cycles of the chemotherapy treatment. There were 6 cases (11.5%) with complete response (CR), 28 cases (53.8%) with partial response (PR), and the overall response rate was 65.4%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. There were no chemotherapy-related deaths.</p><p><b>CONCLUSIONS</b>Oxaliplatin combined with S-1 is an effective and better tolerated chemotherapy treatment for postoperative colorectal cancer patients, with no serious side effects for liver and kidney. Therefore, it can be used as an alternative chemotherapy regimen for postoperative colorectal cancer patients.</p>