Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status.

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.

Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil.

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.

COVID-related hospitalization, intensive care treatment, and all-cause mortality in patients with psychosis and treated with clozapine.

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, amongst patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. amongst those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this.

Physical exercise, obesity, inflammation and neutrophil extracellular traps (NETs): a review with bioinformatics analysis.

Neutrophil extracellular traps (NETs) represent an innate organism defense mechanism characterized by neutrophil release of intracellular material to capture any aggressor agent. Elevated NETs release is associated with increased inflammatory response and related diseases, such as obesity. Chronic physical training is one of the main strategies to treat and prevent obesity. The relationship between physical training and NETs is still under study. The present review, followed by a bioinformatics analysis, demonstrates the meaningful connection between physical exercise, obesity, and NETs. The bioinformatics indicated TNF-α as a leading gene after the ontological analysis followed by positive-interleukin-6 regulation, chemokines, and inflammatory response regulation. The main results pointed to a relevant regulatory effect of physical training on NETs release, indicating physical exercise as a possible therapeutic target on modulating NETs and inflammation.

Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Clozapine treatment and risk of COVID-19 infection: retrospective cohort study.

BACKGROUND: Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia. AIMS: To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK. METHOD: Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use. RESULTS: Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73-3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14-2.72). CONCLUSIONS: These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

Neoadjuvant Chemotherapy With Cisplatin and Gemcitabine Followed by Chemoradiation Versus Chemoradiation for Locally Advanced Cervical Cancer: A Randomized Phase II Trial.

PURPOSE: Although chemoradiation therapy (CRT) with cisplatin remains the standard treatment of patients with locally advanced cervical cancer (LACC), 40% of patients present with disease recurrence. Additional treatment strategies are required to improve outcomes. We conducted a trial to evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) with cisplatin and gemcitabine followed by CRT. METHODS: In this phase II trial, patients with LACC (International Federation of Gynecology and Obstetrics stage IIB to IVA or with positive lymph nodes) were randomly assigned to three cycles of NAC with cisplatin and gemcitabine followed by standard CRT with weekly cisplatin plus pelvic radiotherapy or to standard CRT alone. The primary end point was 3-year progression-free survival (PFS). Secondary end points were response rate, 3-year locoregional control, 3-year overall survival (OS), safety, and quality of life. RESULTS: From 107 patients enrolled in the trial, 55 were randomly assigned to the NAC arm and 52 to the CRT-alone arm. The majority of patients had squamous cell carcinoma (87.8%). After a median follow-up of 31.7 months, NAC was associated with an inferior PFS, with 3-year PFS rates of 40.9% v 60.4% in the CRT arm (hazard ratio, 1.84; 95% CI, 1.04 to 3.26; P = .033). NAC also was associated with a lower OS (3-year OS rate, 60.7% v 86.8%; hazard ratio, 2.79; 95% CI, 1.29 to 6.01; P = .006). After treatment completion, complete response rates were 56.3% in the NAC arm and 80.3% in the CRT arm (P = .008). Toxicities were similar in both arms, with the exception of hypomagnesemia and neuropathy being more common with NAC. CONCLUSION: This study shows that the addition of NAC consisting of cisplatin and gemcitabine to standard CRT is not superior and is possibly inferior to CRT alone for the treatment of LACC.

L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion.

BACKGROUND: Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. MATERIALS AND METHODS: We studied 47 consecutive patients aged 37-88 (61.34±10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. RESULTS: LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. CONCLUSIONS: L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.

Adjuvant Carboplatin and Paclitaxel Chemotherapy Followed by Radiotherapy in High-Risk Endometrial Cancer: A Retrospective Analysis.

PURPOSE: The best adjuvant treatment in high-risk endometrial cancer remains unclear. Although adjuvant chemotherapy seems to improve overall survival (OS) in locally advanced disease, the role of adding radiotherapy is not certain. We evaluated the outcomes of patients with high-risk endometrial cancer treated with adjuvant chemotherapy followed by radiotherapy. PATIENTS AND METHODS: We performed a retrospective analysis of patients with high-risk endometrial cancer (endometrioid histology stages III to IVA or carcinosarcoma, clear cell, or serous histology stages I to IVA) treated with adjuvant carboplatin and paclitaxel, followed by radiotherapy, from 2010 to 2017 at a Brazilian cancer center. The Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: One hundred forty-six consecutive patients were evaluated. The OS rates were 86.2% at 3 years and 75.4% at 5 years. OS was significantly affected by pelvic lymphadenectomy ( P = .001) and positive peritoneal cytology ( P < .001). Three- and 5-year disease-free survival (DFS) rates were 78.3% and 69.5%, respectively. The initial site of recurrence was limited to the pelvis in 4.1% of patients, within the abdomen in 1.3%, and extra-abdominal in 11.6%. Patients with grade 1 or 2 endometrioid carcinoma had better prognosis than patients with endometrioid carcinoma grade 3 or nonendometrioid histology (3-year DFS, 93.67% v 68.5%, respectively; P = .0017). CONCLUSION: Adjuvant carboplatin and paclitaxel, followed by radiotherapy, is effective in high-risk endometrial cancer and associated with low rates of pelvic recurrence, which might be explained by the addition of radiotherapy. The high-risk group is heterogeneous, and the benefit of adjuvant treatment in patients with grade 1 or 2 endometrioid carcinoma is less clear.

Enfermedades infecciosas más frecuentes en pacientes desnutridos con edades comprendidas entre 6 meses a 10 años, habitantes de la parroquia Curiapo, Estado Delta Amacuro, en el período mayo-julio de 2016

Introducción: En pediatría las enfermedades infecciosas constituyen la causa más frecuente de consulta a nivel de atención primaria en salud. La población del presente trabajo de investigación es predominantemente de la etnia Warao y nuestra línea de investigación pretende realizar diagnóstico clínico oportuno tanto de la gravedad del estado nutricional como de las enfermedades infecciosas, respetando la identidad, cultura y autonomía de dicha etnia. Objetivo: Identificar las enfermedades infecciosas más frecuentes por diagnóstico clínico en pacientes desnutridos con edades comprendidas entre 6 meses a 10 años de edad, habitantes de la Parroquia Curiapo, Municipio Antonio Díaz, Edo. Delta Amacuro en el período mayo-julio de 2016. Métodos: La recolección de datos se basó en la entrevista médico-paciente y en la utilización de equipos médicos como estetoscopio, otorrinolaringoscopio, balanza, cinta métrica, gráficas nutricionales de la Organización Mundial de la Salud y las del Estudio Transversal de Caracas. Resultados: De 608 pacientes en estudio, 296 (48,7 %) se encuentran en un estado de malnutrición por déficit, siendo la desnutrición subclínica la predominante con un total de 107 casos. Por otro lado de esos pacientes con malnutrición por déficit, la diarrea y el catarro común conforman las enfermedades infecciosas más frecuentes. Conclusión: El 50 % de la población en estudio presenta algún grado de desnutrición, y la enfermedad infecciosa más frecuente es la diarrea la cual deteriora el estado nutricional del paciente; generándose un círculo pobreza-enfermedad difícil de romper.

Introduction: Pediatric infectious diseases are the most frequent cause of consultation at the level of primary health care. The population of this research belongs to ethnic warao, and our research aims to make timely clinical diagnosis of the severity of the nutritional status and the infectious diseases, respecting the identity, culture and autonomy of this ethnic group. Objective: Our main objective is to identify the most common infectious diseases by clinical diagnosis in undernourished patients between 6 months and 10 years old inhabitants of the Curiapo Parish, Municipality Antonio Diaz, Edo. Delta Amacuro in the period May-July 2016. Methods: Data collection was based in Medical-patient interview, also using medical equipment such as stethoscope, tape measure, othorrinolaringoscope, scales, Nutritional charts of the World Health Organization and the Transversal Study of Caracas for a complete physical examination. Results: In our research we found out that, of 608 patients studied, 296 (48,7 %) are in undernourished deficit level, being subclinical malnutrition the most frequent with 107 cases. On the otherside, those patients with undernourished deficit level, Diarrhea and common cold make up the most frequent infectious diseases in our studied population. Conclusions: We conclude that in the population, about 50 %, have some kind of malnutrition and the most common infectious diseases is diarrhea which decrease the nutritional status of the patients, generating a poverty-disease circle, very difficult to break out.

Carboplatin-based chemoradiotherapy in advanced cervical cancer: an alternative to cisplatin-based regimen?

OBJECTIVE: To evaluate the results of treatment with cisplatin or carboplatin concomitant with radiotherapy (RT) in cases of locally advanced cervical cancer (CC). METHODS: This study is a retrospective analysis of medical records of 184 patients with cervical cancer stage IIB-IVA who were treated at Instituto do Câncer do Estado de São Paulo from May 2008 to December 2012. All patients received complete pelvic region external-beam RT with weekly cisplatin (cis-RT, 40mg/m(2); n=159) or carboplatin (carbo-RT, AUC 2; n=25), followed by high-dose-rate intracavitary brachytherapy (HDR-ICBT). Primary endpoint was progression free survival; secondary endpoints were overall survival and overall response rate, which includes complete and partial responses. RESULTS: Five or more chemotherapy cycles were administered to 87.3% and 84% of the cis-RT- and carbo-RT- treated patients, respectively (p=0.749). Estimated 3-years progression free survival was 59% in the cis-RT group vs 40% in the carbo-RT group (p=0.249). Estimated 3-years overall survival was 70% in the cis-RT group vs 68% in the carbo-RT group (p=0.298). Overall response rate (95.3% cis-RT vs 95.4% carbo-RT; p=0.911) and grade ≥3 toxic effects (8.5% cis-RT vs 11.8% carbo-RT; p=0.757) were similar. In multivariate analysis, only the overall response rate was a significant predictor of survival. CONCLUSIONS: Patients with advanced cervical cancer who are treated with carbo-RT have similar 3-years overall survival, progression free survival, overall response rate, and toxic effects when compared to cis-RT-treated patients. Carbo-RT may be an alternative treatment in patients that cannot receive cisplatin.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness.

OBJECTIVE: Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. METHODS: Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. RESULTS: Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. CONCLUSION: Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.

High-dose interleukin-2 in patients with metastatic melanoma whose disease progressed after biochemotherapy.

The objective of this study was to report our experience with 38 consecutive patients with metastatic melanoma treated with high-dose (HD) bolus interleukin (IL)-2 after disease progression on or after biochemotherapy as the only earlier treatment for metastatic disease. We conducted a retrospective review of all patients with metastatic melanoma treated with HD IL-2 at the Oncology Center of Hospital Sirio-Libanes between October 2000 and December 2009. The treatment consisted of IL-2, of 600,000 U/kg every 8 h for up to 14 doses, followed by 1-week rest and readmission for the second cycle. Responders received up to four additional cycles. Median follow-up was 9 months. The overall response rate was 23.6%, and we found no correlation between earlier response to biochemotherapy and response to HD IL-2. The median survival was 9.5 months for all patients and 36.1 months for the responders. The most frequent grade 3 or 4 adverse events were hypotension, diarrhea, and respiratory distress, and one patient died from septic shock. We concluded that HD IL-2 has clinically meaningful antitumor activity in patients with metastatic melanoma whose disease has progressed after biochemotherapy. This is a treatment alternative in patients with no central nervous system involvement and who are fit enough to tolerate it, regardless of the initial response to biochemotherapy.

Three-phase, liquid-phase microextraction combined with high performance liquid chromatography-fluorescence detection for the simultaneous determination of fluoxetine and norfluoxetine in human plasma.

A three-phase, liquid-phase microextraction using a hollow fibre (HF-LPME) combined with high performance liquid chromatography-fluorescence detection (HPLC-FL) was developed for the analysis of fluoxetine (FLX) and its active metabolite, norfluoxetine (NFLX), in human plasma. An HF-LPME system using a disposable 7-cm polypropylene porous hollow fibre, 5 mL of alkaline plasma solution (donor phase), n-hexyl ether (extraction solvent) and 20 mM hydrochloric acid (acceptor phase) was used in the extraction. The method was validated after optimisation of several parameters that influence LPME efficiency. A reverse-phase LiChrospher 60 RP-Select B column (125 mm x 4 mm, 5 microm particle size) was used with 0.005 M sodium acetate buffer (pH 4.5) and acetonitrile at a 50:50 (v/v) as the mobile phase at a flow rate of 0.6 mL min(-1). In these conditions satisfactory chromatographic resolution and efficiency for the analytes were obtained. Fluorescence detection at 230 nm excitation wavelength and 290 nm emission wavelength was performed. Linearity over a range of 5-500 ng mL(-1), with determination coefficients (R(2)) of 0.9999 and 0.9962 for FLX and NFLX, respectively, was established. Venlafaxine was used as the internal standard for both analytes. Extraction recoveries from plasma samples were 70.9% for FLX and 59.7% for NFLX. The intra-day coefficients of variation (CVs) were below 5.4%, and inter-day CVs were below 13.0%, for both analytes at concentrations of 20, 80 and 160 ng mL(-1). HF-LPME extraction followed by HPLC-FL detection for FLX and NFLX analyses demonstrated excellent sample clean-up and selectivity. This method was simple, cheap, and easy to perform, yielding substantial analytes enrichment. The method was applied to the analysis of samples from 12 patients under fluoxetine treatment and proved suitable for routine therapeutic drug monitoring for this antidepressant.

Combination therapy in high-risk stage II or stage III colon cancer: current practice and future prospects.

Colon cancer represents the second leading cause of cancer-related deaths. For patients who have undergone curative surgery, adjuvant therapy can reduce the risk of recurrence and death from relapsed or metastatic disease. Postoperative chemotherapy with a 5-fluorouracil-based regimen combined with oxaliplatin is the current standard of care for stage III patients. However, there is still controversy in stage II disease about the real impact of adjuvant monotherapy or combined therapy on survival. Better identification of a subgroup of patients with a higher risk of recurrence can select patients who might benefit from adjuvant therapy. For the elderly population, there is a well-established role for postoperative therapy, although the most appropriate regimen remains to be defined. Targeted agents for combined adjuvant therapy in stage II and III colon cancer is a promising area, but to date, there is no evidence supporting its use in this setting. Results from large prospective trials with targeted therapy have been disappointing and new drugs and strategies are needed to define the role of these types of agents in the adjuvant scenario of colon cancer.