Volumetric bone mineral density of the spine predicts mortality in African-American men with type 2 diabetes.

The study showed that in African-American men with type 2 diabetes mellitus (T2D), vertebral volumetric bone mineral density (vBMD) predicts all-cause mortality, independent of other risk factors for death. INTRODUCTION: Compared to European Americans, African Americans have lower rates of osteoporosis and higher rates of T2D. The relationships between BMD and fractures with mortality are unknown in this population. The aim of this study was to determine relationships between vertebral fractures and vertebral vBMD and mortality in African Americans with T2D. METHODS: Associations between vertebral fractures and vBMD with all-cause mortality were examined in 675 participants with T2D (391 women and 284 men) in the African American-Diabetes Heart Study (AA-DHS). Lumbar and thoracic vBMD were measured using quantitative computed tomography (QCT). Vertebral fractures were assessed on sagittal CT images. Associations of vertebral fractures and vBMD with all-cause mortality were determined in sex-stratified analyses and in the full sample. Covariates in a minimally adjusted model included age, sex, BMI, smoking, and alcohol use; the full model was adjusted for those variables plus cardiovascular disease, hypertension, coronary artery calcified plaque, hormone replacement therapy (women), African ancestry proportion, and eGFR. RESULTS: After mean 7.6 ± 1.8-year follow-up, 59 (15.1%) of women and 58 (20.4%) of men died. In men, vBMD was inversely associated with mortality in the fully adjusted model: lumbar hazard ratio (HR) per standard deviation (SD) = 0.70 (95% CI 0.52-0.95, p = 0.02) and thoracic HR per SD = 0.71 (95% CI 0.54-0.92, p = 0.01). Only trends toward association between vBMD and mortality were observed in the combined sample of men and women, as significant associations were absent in women. Vertebral fractures were not associated with mortality in either sex. CONCLUSIONS: Lower vBMD was associated with increased all-cause mortality in African-American men with T2D, independent of other risk factors for mortality including subclinical atherosclerosis.

Intravenous dexamethasone fails to prolong psoas compartment block when assessed by objective pinprick sensory testing: a prospective, randomised, dose-dependent, placebo-controlled equivalency trial.

BACKGROUND: Recent studies have concluded that i.v. dexamethasone can prolong the duration of peripheral nerve blockade. We hypothesized that a 4 mg dose would equally prolong the duration of psoas compartment blocks (PCBs) when compared with 8 mg, and that both doses would prolong the duration when compared with placebo. METHODS: This was a prospective, randomized, placebo-controlled, dose-dependent, equivalency trial with 115 patients undergoing total hip arthroplasty. The patients received a PCB. Subsequently, 15 patients received i.v. normal saline (placebo), 50 patients received i.v. dexamethasone 4 mg, and 50 patients received i.v. dexamethasone 8 mg. The primary outcome was the duration in hours of PCB, determined by serial pinprick assessments. Secondary outcomes included pain scores, time to first analgesic, and opioid consumption. An intention-to-treat-analysis (ITA) and per-protocol analysis (PPA) were performed. RESULTS: The ITA showed that block duration in the 4 and 8 mg groups was equivalent [mean (standard deviation), 18.5 h (8.0) vs 18.1 h (7.1)]. However, neither group differed from placebo [19.6 h (6.7), (4 mg vs placebo), P=0.97; (8 mg vs placebo), P=0.77)]. Postoperative pain scores and opioid consumption were not different between groups. Time to first analgesic was not different between the 4 and 8 mg groups, or the 4 mg and placebo groups. The 8 mg group, however, had a longer time to first analgesic (median of 533 vs 432 min, P=0.047) when compared with placebo, although the significance was not observed in the PPA (P=0.058). CONCLUSIONS: I.V. dexamethasone did not prolong PCB when duration was objectively assessed, or decrease total opioid consumption. However, dexamethasone 8 mg prolonged the time to first analgesic. CLINICAL TRIAL REGISTRATION: NCT 02464176.

The impact of sickle cell trait on glycated haemoglobin in diabetes mellitus.

AIMS: To determine the effect of sickle cell trait on measurement of glycated haemoglobin (HbA(1c)) in African American patients with diabetes mellitus. METHODS: This is a retrospective study including 885 outpatients who underwent HbA(1c) testing. Medical record review and sickle cell trait determinations based on the HbA(1c) assay were performed in African American participants. The relationship between HbA(1c) and serum glucose measurements was analysed. RESULTS: Data were obtained from 385 AA (109 with SCT, 22 with haemoglobin C trait and 254 without haemoglobinopathy) and 500 European American patients. In a model created through multivariate repeated-effects regression, the relationship between HbA(1c) and simultaneous serum glucose did not differ between African American subjects with and without the sickle cell trait, but differed between African American subjects without the sickle cell trait and European Americans (P = 0.0002). CONCLUSIONS: Sickle cell trait does not impact the relationship between HbA(1c) and serum glucose concentration. In addition, it does not appear to account for ethnic difference in this relationship between African Americans and whites.

Is age-dependent, ketamine-induced apoptosis in the rat somatosensory cortex influenced by temperature?

General anesthetics have long been thought to be relatively safe but recent clinical studies have revealed that exposure of very young children (4 years or less) to agents that act by blocking the N-methyl-D-aspartate receptor (NMDAR) can lead to cognitive deficits as they mature. In rodent and non-human primate studies, blockade of this receptor during the perinatal period leads to a number of molecular, cellular and behavioral pathologies. Despite the overwhelming evidence from such studies, doubt remains as to their clinical relevance. A key issue is whether the primary injury (apoptotic cell death) is specific to receptor blockade or due to non-specific, patho-physiological changes. Principal to this argument is that loss of core body temperature following NMDAR blockade could explain why injury is observed hours later. We therefore examined the neurotoxicity of the general anesthetic ketamine in P7, P14 and P21 rats while monitoring core body temperature. We found that, at P7, ketamine induced the pro-apoptotic enzyme activated caspase-3 in a dose-dependent manner. As expected, injury was greatly diminished by P14 and absent by P21. However, contrary to expectations, we found that core body temperature was not a factor in determining injury. Our data imply that injury is directly related to receptor blockade and is unlikely to be overcome by artificially changing core body temperature.

Ethnic variation in the correlation between random serum glucose concentration and glycated haemoglobin.

AIMS: To determine if the relationship between serum glucose concentration and glycated haemoglobin is different between African-Americans and whites. METHODS: Retrospective cross-sectional study comparing the association between glycated haemoglobin and serum glucose levels, based upon ethnicity. Two databases were evaluated: (i) 4215 African-American and 6359 white outpatients who had simultaneous glycated haemoglobin, random serum glucose and creatinine concentration measurements between 2000 and 2007 at the North Carolina Baptist Hospital and (ii) 1021 white and 312 African-American Diabetes Heart Study (DHS) participants. RESULTS: In North Carolina Baptist Hospital clinic attendees, a given glycated haemoglobin was associated with higher serum glucose concentrations in African-Americans compared with whites. In a multivariate model with glycated haemoglobin as the outcome variable, racial differences remained significant after adjustment for serum glucose, age, gender and kidney function. For individuals with a serum glucose between 5.6 and 8.3 mmol/l, the glucose : glycated haemoglobin ratio was 1.03 +/- 0.16 mmol/l/% in white individuals and 0.99 +/- 0.17 mmol/l/% in African-Americans (P < 0.0001). For a glycated haemoglobin value of 7.0%, there was a 0.98-mmol/l difference in predicted serum glucose concentration in 50-year-old African-American men, relative to white. Results were replicated in the DHS, where in a best-fit linear model, after adjustment for glucose, African-American race was a significant predictor of glycated haemoglobin (P < 0.0001). CONCLUSIONS: African-Americans have higher glycated haemoglobin values at given serum glucose concentrations relative to whites. This finding may contribute to the observed difference in glycated haemoglobin values reported between these race groups.

Comparison of glycated albumin and hemoglobin A(1c) levels in diabetic subjects on hemodialysis.

Glycated albumin is thought to more accurately reflect glycemic control in diabetic hemodialysis patients than hemoglobin A(1c) because of shortened red cell survival. To test this, glycated hemoglobin and albumin levels were measured in blood samples collected from 307 diabetic subjects of whom 258 were on hemodialysis and 49 were without overt renal disease. In diabetic subjects with renal disease, relative to those without, the mean serum glucose and glycated albumin concentrations were significantly higher while hemoglobin A(1c) tended to be lower. The glycated albumin to hemoglobin A(1c) ratio was significantly increased in dialysis patients compared with the controls. Hemoglobin A(1c) was positively associated with hemoglobin and negatively associated with the erythropoietin dose in hemodialysis patients, whereas these factors and serum albumin did not significantly impact glycated albumin levels. Using best-fit multivariate models, dialysis status significantly impacted hemoglobin A(1c) levels without a significant effect on glycated albumin. Our results show that in diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.

Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in type 1 diabetic patients.

AIMS/HYPOTHESIS: Altered glucose transporter expression has been implicated in the pathogenesis of diabetic nephropathy. There is increasing evidence that genetic factors convey risk of, or protection from, diabetic nephropathy and that the behaviour of cultured skin fibroblasts from type 1 diabetic patients may reflect these genetic influences. This study aimed to compare GLUT1 mRNA expression levels in skin fibroblasts from type 1 diabetic patients with either rapid ("fast-track", n=25) or slow ("slow-track", n=25) development of diabetic nephropathy and from non-diabetic normal control subjects (controls, n=25). METHODS: Skin fibroblasts were cultured in Dulbecco's Modified Eagle's Medium with 25 mmol/l glucose for 36 h. Total RNA was isolated, and GLUT1 mRNA levels were estimated by microarray analysis and RT-PCR. RESULTS: Levels of GLUT1 mRNA expression in skin fibroblasts from "slow-track" patients were greater than those from "fast-track" patients (p=0.02), as initially detected by microarray. GLUT1 mRNA expression levels were confirmed by RT-PCR to be higher in skin fibroblasts from "slow-track" patients (4.59+/-2.04) than in those from "fast-track" patients (3.34+/-1.2, p=0.02), and were also higher than in skin fibroblasts from control subjects (3.52+/-1.66, p=0.03). There was no statistically significant difference between levels of expression in the "fast-track" patients and the control subjects. CONCLUSIONS/INTERPRETATION: This finding is consistent with the presence of cellular protection factors against diabetic nephropathy in the "slow-track" patients. These factors could be associated with the regulation of the GLUT1 pathway and may be genetically determined.

Prognostic markers in node-negative breast cancer: a prospective study.

BACKGROUND: Despite years of research, it is still unclear which women with node-negative (N-) breast cancer will need adjuvant chemotherapy and which women are being treated unnecessarily. Our goal was to determine which factors best predicted disease free survival (DFS) or cancer-specific overall survival (OS) and, therefore, select the correct patients for treatment. A total of 11 parameters were measured: estrogen receptor (ER), progesterone receptor (PR), age, race, ploidy status, %G0/G1 (% non-DNA synthesis), %S (% S-phase), cathepsin D status, size, stage, and histologic grade. RESULTS: In this prospective study, we followed 556 N- patients diagnosed between 1991 and 1996. The tumors were 56% ER+, 51% PR+, 30% diploid, with a mean %S of 8.9%. The level of cathepsin D ranged from 0.50 to 155 pmol/mg of protein with a mean of 42.9 pmol/mg of protein. There were 87 recurrences (16%) and 72 cancer deaths (13%), with a median follow-up of 7.8 years. Ploidy status (p = 0.01), S-phase activity (p = 0.003), G1 phase activity (p = 0.02) and age (p = 0.01) were able to significantly predict DFS in a univariate manner. All of the measurable factors were significant or borderline significant in predicting OS in a univariate manner except for age, race, and ER status. In multivariate analysis with S-phase included, it was the only remaining factor in DFS and OS; with S-phase excluded, age and ploidy status remained as factors for DFS in stepwise regression, while PR, size, and cathepsin D were the remaining factors that predicted cancer-specific OS. The effect of adjuvant treatment on prognosis was also analyzed. CONCLUSIONS: Both biochemical and clinical parameters have the potential to predict prognosis for N- breast cancer. In this large prospective clinical trial, with a median follow-up of 7.8 years, no individual marker adequately predicted the prognosis for an individual patient. %S activity was the best independent marker, but only 77% of the tumors provided this value. Subset analysis provided improved prognostication, but there were limits to its utility. These data represents a definitive study starting in 1991 and ending in 2002.

Performance of commercial laying hens when six percent corn oil is added to the diet at various ages and with different levels of tryptophan and protein.

Three experiments were conducted to evaluate the use of corn oil in the diet of commercial layers as a method of increasing egg weight. In the first experiment, the performance of commercial layers receiving 6% added corn oil beginning at 18 to 30 wk at 2-wk intervals was evaluated. In the second experiment, comparisons were made between performance of young and old commercial layers when 6% corn oil was added to the diet. The third experiment was conducted to evaluate the effects upon commercial layers when 6% corn oil was added to diets varying in Trp content. In experiment 1, egg weights increased during the first 2 wk that corn oil was added to the diet. During this time, the intake of Trp was greater than or equal to the hen requirements. However, during the last 2 wk of the experiment, when Trp intakes were low, egg weights decreased when corn oil was added to the diet. In experiment 2, egg weights from young and old hens increased during the first 2 wk after corn oil was added to the diet. During the last 2 wk, egg weights from young hens decreased, whereas egg weights from old hens increased. In experiment 3, egg weight was not affected when the diet contained 0.166 or 0.176% Trp. However, egg weights significantly increased when corn oil was added to the diet containing 0.193% Trp. The data in these experiments indicate that the diet of a laying hen must contain a high level of Trp to get an increase in egg weight from the addition of corn oil to the diet. Also the need for other amino acids must be met. Therefore, the hen eats to meet her energy requirement for maximum egg production, and her amino acid intake determines the egg weight.

Threonine requirement of commercial laying hens fed a corn-soybean meal diet.

Two experiments were conducted with Hy-Line W36 hens to evaluate their Thr requirement in a corn-soybean meal diet. Eight experimental diets were used in Experiment 1 with graded levels of Thr: 0.53,0.50, 0.48, 0.45, 0.42, 0.40, 0.37, and 0.35%. Seven experimental diets were used in Experiment 2 with graded levels of Thr: 0.58, 0.53, 0.50, 0.48, 0.45, 0.42, and 0.40%. Supplemental amino acids (AA) were added to all diets to ensure that Thr was the first-limiting AA. Egg production (EP), egg mass (EM), and daily Thr intake were significantly increased with increasing dietary Thr levels. Broken-line regression indicated a daily Thr requirement of 439.0 and 462.1 mg per hen per d in Experiment 1 and of 393.9 and 447.1 mg per hen per d in Experiment 2 for EP and EM, respectively. The Thr requirements to produce 1 g of EM were 8.76 and 9.44 mg in Experiments 1 and 2, respectively.

Betaine does not improve performance of laying hens when the diet contains adequate choline.

An experiment was conducted with Hy-Line W36 hens to determine possible benefits from adding betaine to the diet of commercial laying hens. There was no benefit from the substitution of betaine for choline as measured by egg production, egg weight, egg content, or weight gain.

Re-evaluation of the isoleucine requirement of the commercial layer.

An experiment was conducted with Hy-Line W36 hens to re-evaluate their Ile requirements from a corn-soybean meal diet. Eight experimental diets were fed with Ile levels of 0.60, 0.57, 0.54, 0.51, 0.48, 0.45, 0.42, and 0.39%. Supplemental amino acids (AA) were added to ensure that ILe was the first-limiting AA. Increasing levels of Ile above 0.51% significantly increased egg production (EP), egg weight (EW), and egg mass (EM). Egg production, EW, and EM decreased each time the Ile content of the diet was decreased. Feed consumption (FC) and energy intake were not significantly decreased until the diet contained 0.45% Ile, and, at this time, BW was significantly reduced. Broken-line regression indicated a daily Ile requirement of 449.8, 497.0, and 469.0 mg/d for EP, EW, and EM, respectively, which indicated a requirement of 9.30 mg Ile/g EM.

Prospective trial for the treatment of malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare and often rapidly fatal disease with median survival of 5 to 12 months for untreated cases and 16 months reported after multimodality treatment. We report a prospective clinical treatment study using cytoreductive surgery combined with intraoperative intraperitoneal heated chemotherapy (IPHC) perfusion using mitomycin C for MPM. Twelve patients (11 male with a mean age 51 years) were treated. Seven patients presented with bulky disease and seven with ascites. All underwent exploratory laparotomy with histologically confirmed diagnosis of MPM. Surgical debulking as feasible was performed. Complete gross tumor removal was possible in only one patient. Cytoreduction was followed by a 2-hour closed low-volume IPHC using mitomycin C. One patient died 50 days postoperatively from complications relating to small bowel perforation. Hematologic toxicity of the procedure was minimal. Ascites was controlled in all patients and permanently in 86 per cent of patients presenting with ascites. To date median survival is 34.2 months with median follow-up of 45.2 months. One patient was re-explored for ventral hernia 2 years post-IPHC, had negative peritoneal biopsies, and remains disease-free at 5 years. Given the dismal prognosis associated with MPM the results of treatment with cytoreductive surgery combined with IPHC perfusion are encouraging. The rarity of MPM makes appropriately powered prospective randomized trials unlikely. Therefore, we now offer this approach off protocol; however, further study of this combined modality therapy is warranted.

Farmworker reports of pesticide safety and sanitation in the work environment.

BACKGROUND: Migrant and seasonal farmworkers are at risk for occupational illnesses from pesticide exposure, and the effectiveness of pesticide safety regulations has not been evaluated. It is important to learn from farmworker safety experiences to develop effective measures to improve agricultural workplace safety. METHODS: Formative research included in-depth interviews with farmworkers, farmers, extension agents, and health care providers. Survey research included interviews with 270 minority farmworkers during 1998, and 293 during 1999. RESULTS: Farmworkers and farmers hold different beliefs concerning pesticide safety which affect sanitation practices. Farmworkers report in survey data that farmers do not adhere to regulations mandating training and basic sanitation facilities. CONCLUSIONS: Several points of intervention are available to improve pesticide safety and sanitation. Additional regulation by itself is not an advantageous starting point. The emphasis for intervention must include educating farmers as well as farmworkers.

Birth cohort evidence of population influences on blood pressure in the United States, 1887-1994.

PURPOSE: Mean blood pressure (BP) has declined in the U.S. for several decades. It is unknown to what extent this decline was due to treatment of persons with recognized high BP or to population-wide influences on BP. Treatment would shift only the highest values lower, whereas, population-wide influences on BP would shift the entire distribution downward. METHODS: We examined changes in the distributions of systolic and diastolic BP (SBP, DBP) across birth cohorts born between 1887 and 1975 in 52,646 individuals examined in the National Health (and Nutrition) Examination Surveys between 1960 and 1994. The BP distributions were estimated as functions of age and birth-year to examine changes between birth cohorts. We postulated that the age-adjusted 10th, 50th and 90th percentiles of SBP and DBP had decreased in more recent versus earlier birth cohorts. RESULTS: The series of birth cohorts exhibited successively lower SBP and DBP at low, middle and high percentiles. In general, the 10th percentile of SBP decreased approximately 1.19 mmHg per decade of birth-year, whereas the 50th percentile decreased 2.40 mmHg per decade, and the 90th percentile decreased 4.62 mmHg per decade. A similar pattern of results was seen for DBP. CONCLUSIONS: The entire distribution of both SBP and DBP shifted downward. The downward shifts at the 50th percentile and below unequivocally demonstrate a strong prevention effect in the U.S. population during the period 1887 through 1975. This epidemiologic analysis indicates that population-wide influences can alter favorably the distribution of BP throughout the whole population.

Evaluation of valine requirement of the commercial layer using a corn-soybean meal basal diet.

An experiment was conducted with Hy-Line W-36 hens to evaluate the Val requirement in a corn-soybean meal diet. Eight experimental diets were fed with Val levels of 0.700, 0.665, 0.630, 0.595, 0.560, and 0.525%. A positive control (0.765% Val) was fed. Egg production (EP) was increased by addition of Val to 0.630%. Egg weight (EW) was increased by addition of Val to 0.655%. Broken-line regression indicated a daily Val requirement of 592.5, 677.7, and 619.0 mg/hen per d for EP, EW, and egg contents (EC), respectively. This requirement was 13.1 mg/g of EC.

Quality of life after intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal carcinomatosis.

AIMS: This study assessed the functional status and quality of life (QOL) of patients with disseminated peritoneal cancer (DPC) before and after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (IPHC). METHODS: Patients with confirmed or suspected diagnosis of gastro-intestinal cancer including stomach, pancreas, hepatobiliary and colorectal cancer with peritoneal implants were enrolled in the study. Sixty-four patients completed the Functional Assessment of Cancer Therapy-Colon (FACT-C) scale and several other instruments at baseline. Forty-eight, 40, 39 and 31 patients were assessed at approximately 2 weeks post-surgery, and 3, 6 and 12 months respectively. RESULTS: There was a significant overall effect on the physical (P=0.0025), emotional (P<0.0001) and functional well-being (P=0.0044) subscales and the FACT-C (P=0.0076). Physical and functional well-being scores decreased at post-surgery follow-up and increased relative to baseline at 3, 6 and 12 months. Nineteen per cent, 46%, 59% and 74% of patients resumed greater than 50% of their normal activities post-operatively at 3, 6 and 12 months respectively. A percentage of patients reported depressive symptoms: baseline (28%), post-operatively (33%), 3 months (23%), 6 months (21%) and 12 months (29%). CONCLUSIONS: Cytoreductive surgery followed by IPHC was well tolerated. Most patients returned to baseline or better levels of functioning within 3 months post-treatment.

Bronchoscopy training: current fellows' experiences and some concerns for the future.

OBJECTIVES: To determine current pulmonary fellows' perspectives about their bronchoscopy training. DESIGN: Survey of 59 pulmonary fellows selected by training program directors to represent their institutions. SETTING: "Hands-on" symposium at the CHEST 1998 annual meeting, Toronto, Canada. RESULTS: Fellows reported a mean (+/- SD) of 2.4+/- 0.7 years of training, estimated they had performed 77.7+/-34 bronchoscopies per year, and had generally high estimates of their bronchoscopy proficiency and training. Proficiency estimates correlated with number of procedures cited (r = 0.43, p = 0.001) or level of fellowship training (r = 0.40, p = 0.002). Proficiency ratings (r = 0.63, p = 0.0001) and procedure numbers (r = 0.45, p-0. 0004) correlated with program quality ratings. Approaches to bronchoscopy instruction varied, and most often consisted of one-to-one instruction by faculty (92.5%), lecture-based instruction (74.6%), and case discussions (72.9%). Use of bronchoscopy lectures (p = 0.008) or videos (p = 0.057) were associated with higher self-estimates of proficiency, whereas use of lectures (p = 0.002), a bronchoscopy text (p = 0.009), and one-on-one instruction (p = 0.05) were associated with more highly ranked programs. Major components of training varied among programs. Although most fellows had received instruction encompassed in basic bronchoscopy, fewer had experience with bronchoscopic intubation (71.2%), transbronchial needle aspiration (72.9%), quantitative bacterial culture (64.4%), stent placement (27.1%), laser photocoagulation (25.4%), or cryotherapy (6.8%). Components of bronchoscopy experiences correlated with fellows' estimates of bronchoscopy proficiency and program quality. CONCLUSIONS: Approaches to bronchoscopy instruction and the components of bronchoscopy experiences vary considerably among institutions and are associated with pulmonary fellows' perceptions of bronchoscopy proficiency and training program quality. Definition of an optimum bronchoscopy curriculum remains necessary.

Evaluation of the isoleucine requirement of the commercial layer in a corn-soybean meal diet.

An experiment was conducted with Hy-Line W36 hens to evaluate their Ile requirement in a corn-soybean meal diet. Five experimental diets were fed with Ile levels of 0.61, 0.58, 0.55, 0.52, and 0.49%. Supplemental amino acids (AA) were added to ensure that Ile was the first-limiting AA. Two diets with 0.55 and 0.52% Ile were also fed with higher levels of supplemental AA. A positive control (0.67% Ile) with only Met supplementation was fed, which had previously been shown to support maximum performance. All levels of Ile addition significantly increased egg production (EP), egg weight (EW), and egg contents (EC). Broken-line regression indicated a daily Ile requirement of 589.2, 601.2, and 601.4 mg per day for EP, EW, and EC, respectively, which indicated a requirement of 12.6 mg Ile per gram of EC.

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of gastrointestinal origin.

No standard effective treatment exists for peritoneal carcinomatosis of gastrointestinal origin. The pharmacokinetic advantage of intraperitoneal chemotherapy and the synergy of heat and certain anticancer agents have prompted researchers to investigate intraperitoneal hyperthermic chemotherapy in treating disseminated peritoneal cancers. We have conducted a large Phase II trial to determine the safety and efficacy of aggressive cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC) in treating peritoneal carcinomatosis of gastrointestinal origin. Patients with disseminated peritoneal carcinomatosis of gastrointestinal origin with or without malignant ascites were eligible. After aggressive surgical debulking, patients were administered a 2-hour heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. The major response variable monitored was overall survival. Patients were assessed for toxicity after IPHC administration using the National Cancer Institute Common Toxicity Criteria. Eighty-four patients with peritoneal carcinomatosis of gastrointestinal origin were evaluated for survival and toxicity (colon, n = 38; appendix, n = 22; stomach, n = 19; other gastrointestinal, n = 5). Thirty-nine (46%) patients had malignant ascites at the time of therapy. The operative mortality (30-day) was 6 per cent. Hematologic toxicity was the most common toxicity but was of mild to moderate severity (7 and 4% of patients had grade 3/4 white blood cell or platelet toxicity, respectively). The overall median survival was 14.3 months. The median survival of patients with peritoneal carcinomatosis of appendiceal, colorectal, and gastric origins were 31.1+, 14.6, and 10.1 months, respectively. Significant differences in median survival were seen in patients without and with malignant ascites (27.7 vs 7.6 months; P = 0.0004) and R0/R1 (complete gross tumor resection) versus R2 (gross residual tumor) surgical resection status (28.5+ vs 10.8 months, P = 0.0002). These data suggest that aggressive cytoreductive surgery with IPHC using mitomycin C is safe and effective in treating peritoneal carcinomatosis of gastrointestinal origin. Additional studies and broader applications of this treatment are encouraged.