Daniel Fernandes Saragiotto

Desafios no manuseio peri-operatório de pacientes obesos mórbidos: como prevenir complicações

BACKGROUND AND OBJECTIVES: The incidence of morbid obesity has significantly increased in recent years, especially in developed countries. Excellent results of the surgical treatment of such condition have raised the interest in the anesthetic management of such patients. This study aimed at emphasizing critical issues for anesthesiologists dealing with morbidly obese patients. CONTENTS: Cardiovascular, respiratory, endocrine and metabolic changes have been frequently associated to obesity and may cause significant clinical repercussions in the perioperative period of such patients. Some practical anesthetic issues are discussed in this review. CONCLUSIONS: In addition to emphasizing most significant and frequent complications and their prevention, the importance of PEEP and adequate tidal volumes is also highlighted.

Randomized Phase III Trial Exploring the Use of Long-Acting Release Octreotide in the Prevention of Chemotherapy-Induced Diarrhea in Patients With Colorectal Cancer: The LARCID Trial

PURPOSE Chemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of patients with colorectal cancer. The LAR for Chemotherapy-Induced Diarrhea (LARCID) trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population. PATIENTS AND METHODS Patients with colorectal cancer starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil, capecitabine, and/or irinotecan were randomly assigned to receive octreotide LAR 30 mg intramuscularly every 4 weeks (experimental arm) or the physicians treatment of choice in case of diarrhea (control arm). RESULTS A total of 139 patients were randomly assigned, most of whom received fluorouracil- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n = 68) and 78.9% in the control group (n = 71). Treatment with octreotide LAR did not prevent or reduce the severity of CID. Treatment choices for diarrhea management included loperamide in the majority of patients. No benefit from octreotide LAR was identified in terms of need for diarrhea treatment, opioids, or intravenous hydration or in the rate of hospitalization or quality of life. CONCLUSION This study could not prove the efficacy of octreotide LAR in the prevention of CID.549 Background: Chemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of colorectal cancer patients. The LARCID trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population. METHODS Colorectal cancer patients starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil (5-FU), capecitabine and/or irinotecan were randomized to receive octreotide LAR, 30 mg intramuscularly every 4 weeks, (experimental arm) or the physicians treatment of choice in case of diarrhea (control arm). RESULTS A total of 139 patients were randomized, most of which received 5-FU- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n=68) and 78.9% in the control group (n=71). Treatment with octreotide LAR did not prevent nor reduced the severity of CID. Treatment choices for diarrhea management included loperamide in the majority of cases. No benefit from octreotide LAR was identified in terms of need for diarrhea treatment, opioids, or intravenous hydration, nor in the rate of hospitalization, or quality-of-life. CONCLUSIONS Octreotide LAR is not indicated for the prevention of CID.

Pregabalin for the Prevention of Oxaliplatin‐Induced Painful Neuropathy: A Randomized, Double‐Blind Trial

Abstract Lessons Learned. Pregabalin is a medication that can decrease neuronal hyperexcitability, relieve neuropathic pain, and reach stable plasma levels after a titration period of only a few days. Its use during oxaliplatin infusions was not able to decrease the incidence of chronic, oxalipaltin‐related neuropathic pain, compared with placebo. Background. Patients with colorectal cancer (CRC) receiving oxaliplatin (OXA) develop acute and chronic painful oxaliplatin‐induced peripheral neuropathy (OXAIPN). Acute and chronic OXA‐related neuropathies have different pathophysiological bases, but both lead to a common phenomenon: central sensitization (CS) of nociceptive neuronal networks, leading to increased sensitivity (hyperlgesia, allodynia) in the somatosensory system, the common ground of chronic neuropathic pain. Because CS is related to increased risk of painful OXAIPN, we hypothesized that preemptive use of the anti‐hyperalgesic drug pregabaline (known to decrease CS) during OXA infusions would decrease the incidence of chronic OXAIPN. Methods. Pain‐free, chemotherapy‐naïve CRC patients receiving at least one cycle of modified‐FLOX [5‐FU(500 mg/m2)+leucovorin(20 mg/m2)/week for] 6 weeks+oxaliplatin(85 mg/m2) at weeks 1‐3‐5 every 8 weeks] were randomized (1:1) into the study. Patients received either pregabalin or placebo for 3 days before and 3 days after each OXA infusion and were followed for up to 6 months. Clinical assessments were performed at baseline, at the end of chemotherapy, and after the follow‐up period. The main outcome was average pain at the last visit assessed by the visual analogic scale (0–10) item of the Brief Pain Inventory (BPI). Secondary endpoints were presence of neuropathic pain according to the Douleur Neuropathique‐4 (DN‐4), pain dimensions (short‐ form McGill Pain Questionnaire [MPQ]), Neuropathic Pain Symptom Inventory (NPSI), and changes in nerve conduction studies (NCS) and side effect profile. Results. One hundred ninety‐nine patients (57.0 ± 10.7 years old, 98 female, 101 male) were randomized. Data from 56 patients were not included in the analyses (as they did not receive at least one full cycle of modified FLOX). Data from 78 patients in the pregabalin group and 65 patients in the placebo group were retained for analyses. At the last visit, pain intensity in the pregabalin group was 1.03 (95% confidence interval [CI] = 0.79–1.26), and 0.85 (95% CI = 0.64–1.06) in the placebo group, which did not reach significance. Scores from the BPI, MPQ, DN‐4, NPSI, and NCS and side‐effect profiles and incidence of death did not differ between groups. Quality of life (QoL) score did not differ between groups (placebo = 76.9 ± 23.1, pregabalin group 79.4 ± 20.6). Mood scores were not significantly different between groups (placebo 9.7 [8.1–11.2]; pregabalin 6.8 [5.6–8.0]). Conclusion. The preemptive use of pregabalin during OXA infusions was safe, but did not decrease the incidence of chronic pain related to OXAIPN.

Safety and Efficacy of a Modified FLOX Adjuvant Regimen for Patients With Stage III Colorectal Cancer Treated in the Community

Background The efficacy and safety of the combination of a fluoropyrimidine with oxaliplatin for patients with stage III colorectal cancer (CRC) have been evaluated in selected patients who took part in clinical trials. We evaluated the outcomes of FLOX (bolus fluorouracil [5‐FU] combined with oxaliplatin) in patients with resected stage III CRC treated in the community in a large cancer center. Patients and Methods We performed a retrospective unicenter cohort study of all consecutive stage III CRC patients who received adjuvant chemotherapy with an mFLOX (modified FLOX) regimen. The schedule consisted of 5‐FU bolus 500 mg/m2 and bolus of leucovorin 20 mg/m2 per week for 6 consecutive weeks and oxaliplatin 85 mg/m2 in a 2‐hour infusion at weeks 1, 3, and 5, every 8 weeks. Logistic regression multivariate analyses were used to evaluate prognostic factors for relapse at 2 years, and to investigate potential predictors of Grade ≥3 toxicity. Results A total of 267 consecutive patients were eligible and included. The median age was 59 years and pathological stage was mostly IIIB (68.2%). With a median follow‐up of 24 months, n = 67 patients (25.1%) relapsed, representing a 74.9% rate of disease‐free survival at 2 years. In multivariable analyses, urgent surgery (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.02‐3.48; P = .042), angiolymphatic invasion (OR, 1.92; 95% CI, 1.05‐3.52; P = .034), and any interruption or dose reduction of chemotherapy (OR, 2.37; 95% CI, 1.31‐4.27; P = .004) were predictors of recurrence or death at 2 years. Nine patients (3.4%) died from any cause within 60 days of starting mFLOX. Grade ≥3 toxicity occurred in 98 (36.7%) patients, with diarrhea (n = 43; 16.1%) and neutropenia (n = 38; 15.3%) being the most frequent ones. Peripheral neurotoxicity Grade ≥3 occurred in 5 patients (1.8%). Age 70 years or older (OR, 5.85; 95% CI, 2.5‐13.66; P ≤ .001) was independently associated with a higher risk of a Grade ≥3 adverse events. Conclusion Results suggest that the effectiveness of combining oxaliplatin with bolus 5‐FU in patients in the community is reasonably similar to that obtained in clinical trials. However, community patients presented a higher risk of death, especially for those who were older than 70 years. Adjuvant oxaliplatin should be used carefully and probably restricted to fit patients younger than 70 years in this setting. Micro‐Abstract The efficacy and safety of adjuvant modified FLOX (combination of oxaliplatin with a bolus regimen of fluorouracil) for patients with stage III colorectal cancer were analyzed retrospectively. A total of 267 patients were included, with a 74.9% rate of a 2‐year disease‐free survival and a Grade ≥3 toxicity rate of 36.7%. Age 70 years or older was associated with a higher risk of Grade ≥3 adverse events, suggesting that adjuvant oxaliplatin should be restricted to patients younger than 70 years.

Safety and efficacy of adjuvant modified FLOX for patients (pts) with stage III colorectal cancer (CRC) treated in the community.

760 Background: Based on the NSABP-C07 trial, FLOX became one of the standard adjuvant regimens for pts with stage III CRC. However, its efficacy and safety have not been evaluated outside of clinical trials. Methods: Retrospective analysis of all consecutive stage III CRC pts who received adjuvant chemotherapy with modified FLOX (5-FU bolus 500 mg/m2 and bolus of LV 20 mg/m2 for 6 consecutive weeks and oxaliplatin 85 mg/m2 in 2 hours-infusion at weeks 1, 3 and 5, every 8 weeks). Logistic regression (LR) multivariable models were used to identify predictors of relapse at 2 years and factors associated with grade ≥3 toxicity. Two-sided p<0.05 were significant. Results: From Feb 2007 to Oct 2013, 267 pts were eligible: median age was 59 years, 53.2% were male and 83 (32.2%) were operated emergently. Most pts (68.2%) had stage IIIB CRC, with a median of 21 (range: 1-119) lymphnodes resected. Pathology characteristics: 32 (12%) were poorly differentiated, 132 (49.4%) had angiolymphatic invasion and 75 (28.1%)...

Best Strategy in the Approach of Advanced Colorectal Cancer: Aggressive or Non-aggressive Chemotherapy?

Teatment for metastatic colorectal cancer has advanced beyond single-agent fluoropyrimidine to include various cytotoxic agents, with or without targeted therapies. However, cure rates are still low and limited to those patients who are able to undergo surgery for resection of metastases. The number of possible drug combinations with activity against the disease has skyrocketed and the decision on which treatment to use has become a challenge. Additionally, there is growing agreement that not all tumors present and behave the same way, and that there is a need for further individualization of therapy. Questions remain about how to further optimize therapy between three distinct groups of patients: initially resectable, potentially resectable and definitively unresectable. In this review, we will discuss which patients might benefit better from each strategy.

A multicenter, multinational retrospective analysis of mitomycin C (MMC) in refractory metastatic colorectal cancer (mCRC).

3577 Background: A considerable number of mCRC patients (pts) who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies still have good performance and desire further treatment. MMC has been widely used in this situation, and despite good tolerability, there is no agreement on its role. METHODS In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated pts who received MMC as single agent or in combination for mCRC at three different institutions. RESULTS Of the 109 pts, 30 (27.5%) were treated at M. D. Anderson Cancer Center (USA); 55 (50.5%) at Hospital Sírio Libanês (Brazil) and 24 (22%) at Instituto do Câncer de São Paulo (Brazil). Median age was 54 years old, 57% were male and 94% were performance status ECOG 0 or 1 at diagnosis. MMC was used in second-line in 11%, third-line in 37.6% and fourth-line or beyond in 51.4% of pts. Median TTF on the regimen prior to MMC therapy was 3.7 months. 42% received MMC as single agent while 58% received MMC combinations, mainly with fluoropyrimidines (49%). Severe toxicity was rare (1.8%), with dose reductions in 6.4% of pts. Clinical benefit with MMC, defined as improved symptoms by clinician assessment, was 12%. By response criteria, no radigraphic responses were seen. Median survival was only 4.6 months (95% CI of 4.1 to 5.5). CONCLUSIONS This retrospective data represents the largest reported series of refractory mCRC patients treated with MMC. There were no patients with radiographic response and the low clinical benefit rate is not consistent with an active regimen. The median survival of 4.6 months is similar to the median survival expected for best supportive care in the refractory setting (4.5 months). This lack of activity strongly suggests that mitomycin should not be used in refractory mCRC.