Continuous Venous Infusion Research Articles

Online MR guided dose escalated radiotherapy for organ preservation in distal rectal cancer

IntroductionNon-surgical management of rectal cancer aiming for organ-preservation is an important development to improve rectal cancer treatment. Dose escalated radiotherapy represents one approach to increase clinical complete response (cCR) rates. In the present study we present feasibility and outcome data on rectal cancer patients who were treated with dose escalated radiotherapy using an MR guided online response-adaptive workflow. Material and methodsA total of five patients were treated with 45 Gy in 25 fractions to the mesorectum and the internal iliac lymph nodes and a simultaneous integrated boost to the primary tumor with 50 Gy in 25 fractions on a conventional linac. In addition, weekly response-adaptive boost fractions with 3 Gy per fraction were scheduled on a 1.5 T MR-Linac. Concomitant chemotherapy with 5-fluorouracil was given as continuous venous infusion during the first and last week of treatment. Response was evaluated approximately-three months after the end of treatment and surgery was omitted in case of a clinical complete response (cCR) or a near cCR. Toxicity was graded by using PRO-CTCAE, Quality of life by the EORTC-QLQ-C30 questionnaire and continence according to the Wexner scale. ResultsResponse-adaptive dose escalated radiotherapy was feasible and well tolerated by all patients. Four reached a clinical complete response, one had a local excision confirming pathological complete response (pCR). All PRO-CTCAE grade 3 toxicities resolved within six months after the end of treatment. Quality of life and continence scores during follow-up were comparable to baseline levels. ConclusionDose-escalated online response-adaptive MR-guided radiotherapy appears to be a very promising treatment with the goal of organ preservation in rectal cancer leading to high response rates, excellent organ function and limited side effects. Further prospective evaluation is needed.

Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic\u2013pharmacodynamic model in gastrointestinal cancer patients

PurposeTo describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach.MethodsThirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m2/day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m2/day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM. Absolute leukocyte counts were described by a semi-mechanistic myelosuppression model. Covariate relationships were evaluated to explain the possible sources of variability in 5FU pharmacokinetics and pharmacodynamics.ResultsTotal clearance of 5FU correlated with body surface area (BSA). Population estimate for total clearance was 249 L/h. Clearances of 5FU and 5FUH2 fractionally changed by 77%/m2 difference from the median BSA. 5FU central and peripheral volumes of distribution were 5.56 L and 28.5 L, respectively. Estimated 5FUH2 clearance and volume of distribution were 121 L/h and 96.7 L, respectively. Baseline leukocyte count of 6.86 × 109/L, as well as mean leukocyte transit time of 281 h accounting for time delay between proliferating and circulating cells, was estimated. The relationship between 5FU plasma concentrations and absolute leukocyte count was found to be linear. A higher degree of myelosuppression was attributed to combination therapy (slope = 2.82 L/mg) with cisplatin as compared to 5FU monotherapy (slope = 1.17 L/mg).ConclusionsBSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin.

897-P: Continuous Glucose Monitoring (CGM) in Management of Patients with Severe Traumatic Brain Injury

Hyperglycemia after severe traumatic brain injury patients is frequent finding that has impact on clinical outcome and increases mortality. Management of increased blood glucose but also prevention of hypoglycemic episodes are crucial in those patients. The aim of our observation is to analyze the effect of CGM in management of diabetic patients with severe traumatic brain injury (TBI) Our study included 37 patients (20 men, 17 women, mean age 34.6±9.7 years) hospitalized in Intensive Care Unit. All patients have diabetes with duration 7.3±5.8 years, with severe TBI and Glasgow coma scale of 8 or less. For monitoring of glucose level patients real-time CGM - Paradigm Medtronic Minimed was placed for 5 days period. Simultaneous glucose measurements were performed four times daily. Patients received continuous venous infusion of fast acting insulin for maintaining glucose level below 10mmol/l. Number of CGM measurements was significantly higher compared to conventional monitoring of blood glucose (288 measurements vs. 4 measurements daily, p<0.05). None of the patients showed any problems with CGM-device like technical problems and irritation or allergy at the site of sensor insertion. More than one hypoglycemic episodes (blood glucose below 3.9mmol/) were detected in 37.8% (n=14) based on CGM data and only in 18.9% (n=7) from four-point profiles. CGM defined that patients spent about 54.9±12.2% of observed period in hyperglycemic state (blood glucose above 10mmol/l) while with conventional monitoring this time was 28.7±9.8% (p<0.05). Data from CGM allow more precise adjustment of insulin infusion for maintaining glucose in targets and preventing complications of insulin treatment. Results from real-time CGM has impact on the glycemic control in diabetic patients with severe TBI and should be recommended in protocols for management and used whenever it is possible. Disclosure I. Daskalova: None. T. Totomirova: None. N. Petrov: None. M. Arnaudova: None.

Donor Selection and Prophylactic Strategy for Venous Thromboembolic Events in Living Donors of Liver Transplantation Based on Results of Thrombophilia Screening Tests.

BackgroundWe reported a strategy of thrombophilia testing-guided venous thromboembolic events (VTE) prophylaxis for living donors of liver transplantation in 2011. The aim of the present study was to evaluate the safety and efficacy of this protocol for VTE prophylaxis.Material/MethodsThrombophilia testing, including protein S (PS), protein C (PC), antithrombin (AT) III, and anti-phospholipid antibody (APLA), was performed in 306 living donor candidates between July 2005 and June 2016. Donors who met any of the criteria of PS <60%, PC <64%, AT-III <70%, and positive APLA were classified into the borderline group and received continuous venous infusion of heparin immediately after surgery, in addition to use of elastic stockings and intermittent pneumatic compression (IPC) until patients were ambulatory. Other donors who were classified into the normal group used elastic stockings and IPC with no anticoagulants. The efficacy and safety endpoints were VTE occurrence and bleeding events, respectively.ResultsPS was considerably decreased in 3 candidates and PC was considerably reduced in 1 candidate, and they were excluded for high risk of VTE. Seventeen candidates in the borderline group and 137 in the normal group underwent donor surgery. One donor in the borderline group developed a wound hematoma. Postoperative complications were similar between the 2 groups. None of the donors in either group developed VTE.ConclusionsThrombophilia testing-guided VTE prophylaxis is safe and may contribute to reduced VTE risk in donors, although further investigations are warranted to assess the necessity of thrombophilia testing prior to surgery among living donors.

Randomized controlled Phase III study comparing hepatic arterial infusion with systemic chemotherapy after curative resection for liver metastasis of colorectal carcinoma: JFMC 29–0003

The feasibility and efficacy of adjuvant hepatic arterial infusion (HAI) in preventing the development of liver metastases in patients with advanced colon carcinoma have not been validated. The aim of this randomized controlled study was to compare the feasibility of HAI and the protective effect against liver metastasis after curative resection to those of systemic chemotherapy. Between July 2000 and June 2003, 91 patients were enrolled. Patients were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary endpoint was overall survival (OS). In the WHF group, the cumulative failure rate of hepatic arterial catheterization was 16.7% at 6 months. The occurrence of grade 3 adverse events was comparable between the groups. The 5-year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164). CVI tended to show a protective effect against liver metastasis regarding the 5-year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P = 0.037). HAI therapy has a certain protective effect against liver metastasis after curative resection in patients with colorectal cancer. However, this therapy did not contribute to any marked improvement in their overall survival.

A Single Center Phase II Study of Continuous Infusion of Low-dose 5- fluorouracil for Heavily Pretreated Patients With Metastatic Colorectal Cancer

Objective: Many patients with metastatic colorectal cancer (MCRC) cannot afford the targeted therapy in China. There is no standard treatment when these patients whose tumors relapsed following the first- and second- line chemotherapy. The goal of the present study is to evaluate the efficacy and safety of continuous intravenous infusion (CIV) of low-dose 5-fluorouracil5-FUfor heavily pretreated patients with MCRC. Methods: Twenty-three heavily pretreated patients with MCRC received 5-FU 200 mg/m2 per day as CIV for more than 30 days. Efficacy and safety was evaluated after one cycle of chemotherapy. Results: No patient achieved complete response (CR), 2 patients partial response (PR), 8 patients stable disease (SD), and 13 patients progression disease (PD). Response rate (RR) was 8.7%, disease control rateCR+PR+SD was 43.5%Toxicity was mild. Conclusion: This study showed that continuous venous infusion of low-dose 5-fluorouracil was moderately active and well tolerated in heavily pretreated patients with MCRC. Keywords: Low-dose 5-fluorouracil, continuous intravenous infusion, metastatic colorectal cancer.

Very low levels of H2S in the blood are needed to affect the medullary respiratory neurons and the arterial chemoreceptors in‐vivo

Endogenous H2S has been proposed to be involved in the generation of breathing by the brainstem respiratory neurons (RN) and to transduce the effects of hypoxemia in the arterial chemoreceptors (CB). However, H2S at concentrations which should inhibit the cytochrome C oxidase (CCO) activity, i.e. above 30 μM, have been used in‐vitro to stimulate the CB (30–100 μM) or to affect the RN (200 μM). We determined the concentration of H2S dissolved in the arterial blood able to stimulate the CB and to stop breathing in 8 spontaneously‐breathing anesthetized rats. H2S partial pressure (PaH2S) and gaseous concentrations were determined in the arterial blood from alveolar PH2S during continuous venous infusion of NaHS. This approach overcomes most of the issues of other techniques that directly measure H2S dissolved in the blood. A stimulation of breathing occurred for a PaH2S of 0.007±0.003 mmHg, corresponding to a concentration of gaseous and total dissolved H2S of at most 0.63±0.31 μM and 1.89±0.93 μM. A rapid reduction in breathing occurred at a PaH2S of 0.042±0.020 mmHg, gaseous H2S of 3.68±1.72 μM, and total dissolved H2S of 11.04±5.16 μM. H2S affects the CB and RN in‐vivo via mechanisms independent of CCO. Whether these low levels of dissolved H2S are low enough to be compatible with the levels of H2S endogenously produced remains to be determined. Support provided by NIH grant 1R21NS080788–01.

Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m(2) per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m(2) per day, Monday to Friday, plus irinotecan, 50 mg/m(2) once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm2. High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.

Concurrent Chemoradiotherapy in the Treatment of Locally Recurrent Rectal Cancer

Long course concurrent chemoradiotherapy provides potential tumor downstaging. When local recurrent rectal cancer without distant metastases is diagnosed, a potentially curative resection can be performed. The aim of this study was to assess the outcome of concurrent chemoradiotherapy in treating isolated local recurrent rectal cancer. Patients (n=102) with isolated local recurrent rectal cancer within the pelvis were scheduled for concurrent chemoradiotherapy, consisting of pelvic irradiation with a total dose of 50.4 Gy in 28 fractions. Chemotherapy was administered concurrently and included 85 mg/m2 oxaliplatin by venous infusion over 2 h on day 1, followed by 1,200 mg*m-2*day-1 of continuous venous infusion for 2 days. This regimen was repeated every 2 weeks for 6 cycles. The overall survival rate, responses, disease-free interval and toxicities were assessed. A total of 96 patients completed planned concurrent chemoradiation. Complete clinical responses were found in 13 of the 96 patients (14%), partial responses in 59 (61%), stable disease in 21 (22%) and disease progression in 3 (3%). The overall survival and disease-free survival rates in all the 96 patients were 45% and 14%, respectively. The treatment of locally recurrent rectal cancer is complicated. Concurrent chemoradiation can increase disease-free survival and overall survival by increasing complete resection rate of locally recurrent tumors and even complete response of the tumors. Ongoing treatment strategies aim to enhance response rates and to accurately assess the extent of local recurrent tumor response to concurrent chemoradiation.

The efficacy of continuous infusion of low dose dexmedetomidine for postoperative patients recovering in general wards

The efficacy of continuous infusion of low dose dexmedetomidine for postoperative patients recovering in general wards

A case of spontaneous rupture of a uterine superficial varicose vein in midgestation

A 25-year-old gravida two, nulliparous pregnant woman complained of a sudden onset of severe pain in the right lateral abdominal area and went to hospital at 28 weeks and 5 days' gestation. Since cyclic uterine contractions were observed, a diagnosis of preterm labor was made and tocolysis was carried out by the continuous venous infusion of ritodorine. She was transferred to Hamamatsu University Hospital and an emergency cesarean section was carried out due to non-reassuring fetal status. A hemoperitoneum of 850 mL was observed in the peritoneal cavity and an immature male baby weighing 1140 g was born. There was bleeding from a ruptured superficial varicose vein in the right lateral portion of the uterus, which was stopped by compression and the attachment of oxidized cellulose cotton. The clinical management and differential diagnosis were discussed.

Effect of Infused Norepinephrine Dosage on Pressure Ulcers in Perianesthesia Care Unit Patients: A Pilot Study

To determine whether treatment with moderate-high dose norepinephrine is a contributory cause increasing the risk of pressure ulcer development in critical postoperative, mechanically ventilated, hyperglycemic patients. A pilot clinical cohort study was conducted in a PACU in a tertiary hospital. A convenience sample of 16 hyperglycemic patients undergoing mechanical ventilation with at least 24 hours' stay in the PACU were divided into two groups of eight according to dosage of norepinephrine infusion at any moment during the days monitored. One group received ≥ 2.5 mg/hour, and the other received <2.5 mg/hour. The dose of norepinephrine administered by continuous venous infusion and the occurrence of stage II pressure ulcers were recorded. The proportion of patients with pressure ulcers in the group receiving moderate-high dose of norepinephrine was 50% compared with 0% in the low-dose group (P = .038). The odds ratio for daily average norepinephrine administered (mg/hour) was 2.21 (95% CI = 1.27 to +infinite); exact P = .0049. The odds ratio for daily average norepinephrine administered adjusting for weight (mg/kg/hour) was 3.05 (95% CI = 1.299 to +infinite); exact P = .0016. Moderate-high dose norepinephrine is a contributory cause that significantly increases the risk of pressure ulcer development in certain short-stay PACU patients.

Correlation between basal bilirubin levels and survival in advanced colorectal carcinoma treated with CPT-11-based chemotherapy: A study of the Gruppo Oncologico Italia Meridionale (G.O.I.M.)

BackgroundThis study was carried out to evaluate total basal bilirubin levels as a predictive factor for survival and toxicity in patients with advanced colorectal carcinoma treated with CTP-11-based regimens. Patients and methodsThe analysis was carried out on a data base including 287 patients affected by advanced colorectal carcinoma all treated with CPT-11 plus bolus and continuous venous infusion intravenous folinic acid and 5-fluorouracil on a biweekly schedule (FOLFIRI regimen). Patients were divided into four groups according to basal bilirubin levels as follows: <0.49mg/dl; >0.50 and <0.99mg/dl; >1.00 and <1.49mg/dl; >1.50mg/dl. Analysis of overall median survival and time-to-progression were correlated to performance status at entry, volume of liver metastases, and carcinoembrionary antigen. ResultsGlobal statistical analysis showed that bilirubin levels were strongly correlated with time-to-progression and overall survival in a statistically significant fashion (p<0.0001). The size of liver metastases represents the only study parameter which is correlated to basal bilirubin levels in a statistically significant fashion. Neutropaenia and diarrhoea were also correlated to baseline bilirubin levels in a statistically significant manner (p=0.001). ConclusionsData reported in this study support the observation that basal bilirubin levels are a biomarker able to predict, at least in part, the clinical efficacy and toxicity of CPT-11-based chemotherapy in patients with advanced colorectal carcinoma.

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: A prospective randomized trial

Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.

Chemoradiation With Concomitant Boost Followed by Radical Surgery in Locally Advanced Cervical Cancer: A Dose-Escalation Study

Aim of this study is to evaluate the feasibility of an accelerated fractionation radiotherapy by concomitant boost in locally advanced cervical cancer patients, to explore the maximum tolerated dose (MTD) of radiation through a dose-escalation scheme, and to verify if increasing the radiation dose would result in a higher rate of pathologic complete response. During the first and the last week of treatment, a combination of cisplatin (20 mg/mq/d, IV, days 1-4) and 5-fluorouracil (1 g/mq/d, continuous venous infusion, days 1-4) was administered. The dose escalation of external radiotherapy was delivered on the primary tumor, using the concomitant boost technique (CB, 90 cGy per fraction), delivering 3 different dose levels: (1) 1 weekly boost for a total dose of 4320 cGy; (2) 2 weekly boosts, total dose 4680 cGy; (3) 3 weekly boosts, total dose of 5040 cGy. Eighteen patients were submitted to a radiochemotherapeutic schedule of 3960 cGy in 22 fractions on pelvic lymph nodal stations. The MTD of radiation was not reached, being the only toxicities registered neutropenia G3 (n = 4), thrombocytopenia G3 (n = 1), stomatitis G3 (n = 1), diarrhea G3 (n = 2) easily managed. Six weeks after the end of radiochemotherapy, 17 patients were submitted to radical surgery, and are therefore evaluable for pathologic response. Among them, 15 complete remissions (88.2%, including 3 microscopical partial response), 1 partial response (5.9%), and 1 progression (5.9%) have been observed. These results demonstrate, even if in a small study, that this regimen of concurrent chemoradiation followed by radical surgery is well tolerated.

Postoperative Radiotherapy of Glioblastoma Multiforme

Different factors influence glioblastoma patients' prognosis. The aim of this retrospective, explorative analysis was to define the role of recent treatment strategies and to examine the value of different prognostic factors. A total of 110 patients was analyzed. Complete resection, partial resection, and biopsy was accomplished in 69, 22, and 19 patients, respectively. 56 patients received conventionally fractionated radiotherapy with a median total dose of 60 Gy, 2 Gy daily. 54 patients received hyperfractionated accelerated radiotherapy with a median total dose of 54 Gy, 2 × 1.8 Gy daily. 20 patients had concomitant temozolomide (50–75 mg/m2/d), and 20 patients concomitant topotecan (0.5 mg/m2 as continuous venous infusion over 21 days). 37 patients received temozolomide as salvage therapy. Median overall (OS) and disease-free survival (DFS) were 8.7 and 4.8 months. After complete resection, partial resection, and biopsy, OS was 9.5, 8.5, and 5.5 months, respectively. OS was 8.5, 13.8, and 8.2 months for radiotherapy alone, concomitant temozolomide, and concomitant topotecan, respectively. Hazard ratio was 0.29 (OS; p = 0.002) and 0.32 (DFS; p = 0.003) for concomitant temozolomide compared to radiotherapy alone. Topotecan led to an increased toxicity. With 9.7 months for conventionally fractionated radiotherapy and 8.1 months for hyperfractionated radiotherapy, OS differed significantly (p = 0.003, log-rank test). OS in patients with RPA (recursive partitioning analysis) score III, IV, V, and VI was 14.1, 10, 9.5, and 5.8 months (p = 0.003, log-rank test). In the univariate (p = 0.0001, log-rank test) and multivariate analysis (p = 0.002, Cox regression), salvage temozolomide led to a statistically significant survival benefit (10.6 vs. 7.7 months). Concomitant topotecan or the use of hyperfractionated radiotherapy did not show to be superior in outcome in this retrospective analysis. Topotecan led to an increased toxicity. An attempt at complete resection is justified. Temozolomide should be integrated in therapy initially. As salvage therapy, temozolomide is also effective.

Relationship between 5‐fluorouracil exposure and outcome in patients receiving continuous venous infusion with or without concomitant radiotherapy

Toxicity and response are correlated with plasma 5-fluorouracil (5-FU) concentration in patients treated with 5-FU at a dose of 1000 mg m(-2) day(-1). Head and neck cancer patients are treated with various therapeutic regimens, including chemotherapy with 5-FU at a dose of 600 mg m(-2) day(-1) with radiotherapy. We investigated the plasma concentration-effect relationship for this regimen, with the aim of developing recommendations for dose adjustment. Patients received 5-FU at doses of 600 or 1000 mg m(-2) day(-1), as a continuous infusion over 4 or 5 days, with or without radiotherapy for the 600 mg m(-2) day(-1) regimen. The area under the curve (AUC) for 5-FU concentration was estimated, based on a single morning blood sample taken each day during treatment. AUC values were compared between patients with and without toxicity. This simplified method for AUC estimation was compared with the standard two-samples-per-day method in an independent group of 50 patients. Forty-six patients, corresponding to 115 courses, were included in this prospective study. Considerable interindividual variability in estimated AUC was observed for both doses. Grade 3-4 toxicity occurred in 10 and 21% of patients given doses of 600 and 1000 mg m(-2) day(-1), respectively. Ths study confirmed the relationship between plasma 5-FU concentration and toxicity previously reported for 1000 mg m(-2) day(-1), but found no such relationship for the 600 mg m(-2) day(-1) regimen with concomitant radiotherapy. Our results do not support the use of therapeutic drug monitoring to improve tolerance for the 600 mg m(-2) day(-1) regimen with concomitant radiotherapy. A simplified method is proposed for 5-FU monitoring for the 1000 mg m(-2) day(-1) regimen.

Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: a comparative study with remifentanil in gynecologic videolaparoscopic surgery

Study Objective To evaluate the capacity of dexmedetomidine (DEX), an α 2 adrenergic agonist drug, as a substitute for remifentanil (REM), a potent opioid, in total intravenous anesthesia (TIVA), in patient undergoing gynecologic videolaparoscopy. Design Randomized, single-blinded study. Setting University-affiliated hospital. Patients 30 ASA physical status I and II women, patients (22-56 yrs), scheduled for gynecologic videolaparoscopy. Interventions Patients were anesthetized with DEX or REM in continuous venous infusion, associated with propofol, in a target-controlled infusion. Measurements Heart rate, mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma glucose, and cortisol were determined before anesthetic induction, 5 minutes after tracheal intubations and 30 minutes after initial surgical incision. Extubation and orientation times, and postanesthesia care unit (PACU) discharge times were noted. Main Results Blood cortisol levels were higher in the DEX group than in the REM group at 30minutes after surgical incision. Cortisol levels decreased as a function of time in the REM group, whereas intheDEX group they decreased in the second sample and returned to basal levels at 30minutes. Hyperglycemia was higher in DEX than in REM during the second and third sample collection. However, glucose increased as a function of time in both groups. Analysis of MBP and DBP indicated adecrease in blood pressure at 5 minutes after tracheal intubations in both groups. At 30minutes afterincision, MBP and DBP returned to basal levels in the DEX group, whereas the variables were significantly lower in the REM group. There were significant differences between groups for systolic blood pressure and heart rate at 5 and 30 minutes after incision with a greater decrease in REM. The extubation and orientation times were significantly increased in the DEX group, when compared with those of the REM group. There were no differences in postanesthesia care unit discharge times between groups. Conclusions Dexmedetomidine was a clinically effective drug as a REM substitute in TIVA, during minimally invasive video gynecologic surgical procedures; however, patients anesthetized with DEX showed a more prolonged recovery time for some parameters such as orientation and extubation times.

Mitomycin-C/5-Fluorouracil/Leucovorin and Hyperfractionated Radiation Therapy for Rectal Carcinoma: A Phase II Study with Long-Term Follow-up

Purpose Preoperative chemotherapy followed by surgery and adjuvant chemotherapy is a standard treatment for most patients with rectal cancer. We aimed to determine efficacy and tolerability of preoperative mitomycin, fluorouracil (5-FU), and leucovorin (LV) concurrent with hyperfractionated radiation therapy (RT) followed by surgery and adjuvant chemotherapy. Patients and Methods Patients with clinical stage II/III disease were treated with mitomycin 10 mg/m 2 on day 1, continuous venous infusion 5-FU 600 mg/m 2 per day for 96 hours, and oral LV 25 mg every 6 hours on days 1–5. All patients received concurrent RT in fractions of 150 cGy twice daily beginning on day 1. Unfixed tumors received 3000 cGy, whereas fixed tumors received a dose of 4500 cGy. Patients then underwent resection and postoperative adjuvant chemotherapy with oral LV and continuous venous infusion 5-FU 600 mg/m 2 per day on days 1–5 on a 28-day cycle for 6 cycles. Primary endpoints were to determine the rate of pathologic response and downstaging, long-term locoregional control, progression-free survival, and overall survival. Results Between the years 1993 and 2000, 83 patients were enrolled. Eighteen patients (31%) were downstaged. Six patients (7%) had pathologic complete response. Median follow-up was 62 months with a 5-year overall survival of 71%. Local control rate was 96%. Treatment was well tolerated with stomatitis, diarrhea, and radiation proctitis being the most common toxicities. Conclusion This regimen is effective in the treatment of rectal carcinoma. The favorable toxicity profile of mitomycin and hyperfractionated RT allows these strategies to be utilized with the newer chemotherapies for this disease.

5-Fluorouracil and Weekly Oxaliplatin Combined with Radiotherapy for Locally Advanced Rectal Cancer: Surgical Complications and Long-term Results

We undertook this study to evaluate early surgical complications and long-term results after preoperative radiotherapy and chemotherapy (RCT) using 5-fluorouracil (5-FU) and oxaliplatin (OXA) for rectal cancer. Forty six TNM stage II-III rectal cancer patients were studied, who were given preoperative RT (50.4 Gy/28 fractions) combined with 5-FU (200-225 mg/m(2)/day by continuous venous infusion) and weekly OXA (25-60 mg/m(2)). Major complications and reoperations were recorded overall, whereas outcome analyses were performed only for patients who received the recommended regimen dosage. Forty three patients (M:F, 25:18; median age 59 years) were available for analysis. All patients received the planned RT dose. There were no postoperative deaths; seven patients had early major surgical complications, four requiring re-operation. One additional patient had a second surgical procedure due to a duodenal fistula complicating the resection of an aortic aneurysm performed concomitantly with rectal cancer surgery. At a median follow-up of 49 months, two of the 23 patients treated at the recommended doses developed recurrence (one local, and one local and distant), and two died of cancer progression. Following the Kaplan-Meier method, the estimated 5-year overall and disease-free survival rates were 92 and 89%, respectively. The preoperative RCT regimen used in the present study incurs a low rate of recurrence with an acceptable surgical morbidity.