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Biomedical subjects

A D Stephens

Publications and source records attributed to A D Stephens.

At least 19 recordsLinked to original sources
PubMed2000

Hemodynamic and cardiac function parameters during heated intraoperative intraperitoneal chemotherapy using the open "coliseum technique".

BACKGROUND: Heated intraoperative intraperitoneal chemotherapy achieves high peritoneal concentrations with limited systemic absorption and has become an important tool in the management of patients with peritoneal carcinomatosis from low-grade malignancies such as pseudomyxoma peritonei and in selected cases of high-grade tumors such as colon adenocarcinoma. When the closed abdomen technique is used, its perioperative toxicity seems to be related to the hemodynamic and cardiac function changes associated with increased body temperature and increased intra-abdominal pressure. METHODS: Hemodynamic and cardiac function variables during heated intraoperative intraperitoneal chemotherapy, using an open abdomen "coliseum technique," were measured in 15 patients with the use of a noninvasive esophageal Doppler monitor. RESULTS: The hemodynamic and cardiac function changes were characterized by an increased heart rate, increased cardiac output and decreased systemic vascular resistance associated with an increased body temperature, and decreased effective circulating volume with the urinary output tending to decrease as the therapy progressed. CONCLUSION: Heated intraoperative intraperitoneal chemotherapy with the open abdomen coliseum technique induces a hyperdynamic circulatory state with an increased intravenous fluid requirement and avoids changes because of increased intra-abdominal pressure. Hemodynamic and cardiac stability, as documented by normal blood pressure and adequate urinary output, can be achieved by liberal intravenous fluids, titrated to frequent urinary output determination.

Adult↗
PubMed1999

Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the coliseum technique.

BACKGROUND: Peritoneal carcinomatosis from gastrointestinal cancers is a fatal diagnosis without special combined surgical and chemotherapy interventions. Guidelines for cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) by using the Coliseum technique have been developed to treat patients with peritoneal carcinomatosis and other peritoneal surface malignancies. The purpose of this study was to analyze the morbidity and mortality of patients undergoing cytoreductive surgery and HIIC by using mitomycin C. METHODS: Data were prospectively recorded on 183 patients who underwent 200 cytoreductive surgeries with HIIC between November 1994 and June 1998. Seventeen of the 183 patients returned for a second-look surgery plus HIIC. All HIIC administrations occurred after cytoreduction and used continuous manual separation of intra-abdominal structures to optimize drug and heat distribution. Origins of the tumors were as follows: appendix (150 patients), colon (20 patients), stomach (7 patients), pancreas (2 patients), small bowel (1 patient), rectum (1 patient), gallbladder (1 patient), and peritoneal papillary serous carcinoma (1 patient). Morbidity was organized into 20 categories that were graded 0 to IV by the National Cancer Institute's Common Toxicity Criteria. In an attempt to identify patient characteristics that may predispose to complications, each morbidity variable was analyzed for an association with the 25 clinical variables recorded. RESULTS: Combined grade III/IV morbidity was 27.0%. Complications observed included the following: peripancreatitis (6.0%), fistula (4.5%), postoperative bleeding (4.5%), and hematological toxicity (4.0%). Morbidity was statistically linked with the following clinical variables: duration of surgery (P < .0001), the number of peritonectomy procedures and resections (P < .0001), and the number of suture lines (P = .0078). No HIIC variables were statistically associated with the presence of grade III or grade IV morbidity. Treatment-related mortality was 1.5%. CONCLUSIONS: HIIC may be applied to select patients with peritoneal carcinomatosis from gastrointestinal malignancies with 27.0% major morbidity and 1.5% treatment-related mortality. The frequency of complications was associated with the extent of the surgical procedure and not with variables associated with the delivery of heated intraoperative intraperitoneal chemotherapy. The technique has shown an acceptable frequency of adverse events to be tested in phase III adjuvant trials.

Adult↗
PubMed1997

The use of automated HPLC to detect and quantitate haemoglobins.

The introduction of automation for haemoglobinopathy screening is an important advance in technology for haematology laboratories. This paper evaluates the utility of an automated HPLC instrument, the Bio-Rad 'Variant' for the detection and quantitation of the normal haemoglobins (Hb A, A2 and F) and the common abnormal haemoglobins (Hb S, C, DPunjab, E, OArab and Lepore) which need to be evaluated in laboratories undertaking carrier and/or neonatal screening for sickle cell and thalassaemia. The instrument only uses a small amount of whole blood (5 microliters), a 3 mm disc from a Guthrie spot may also be used for analysis of samples from neonates. It uses a 100 place automatic sampler with a cycle time of 6.5 min for adult samples (using the 'Beta Thalassaemia Short' reagent pack) and 3 min for neonatal samples. The automatic sampler also allows samples to be analysed 'out of hours'. A 'STAT'; position allows urgent samples to be analysed before, or during, a routine analytical run. All reagents, other consumables and application notes are provided by the suppliers. Other types of reagent packs, such as the 'Sickle Cell Short' for neonatal screening were not assessed during this study.

Adult↗
PubMed1996

Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinoma has been regarded as a uniformly lethal clinical entity. A treatment plan combining cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy (HIIC) was devised and tested to treat such patients. The purpose of this study was to evaluate the morbidity and mortality associated with this treatment approach. METHODS: Sixty patients with peritoneal carcinomatosis from adenocarcinoma of the colon or appendix were included in the study. Extensive cytoreductive surgery was combined with heated intraperitoneal mitomycin in an intraoperative lavage technique followed by one cycle of early postoperative intraperitoneal 5-fluorouracil. Eleven clinical variables were selected and statistically correlated with morbidity and mortality. RESULTS: Twenty-five complications occurred in 21 patients (morbidity = 35%). Morbidity related to gastrointestinal function included anastomotic leak (n=6), bowel perforations (n=5), bile leak (n=3), and pancreatitis (n=2). Four patients presented with severe hematologic toxicity (Grade 3 or 4). There were three cases of postoperative bleeding, one case of abdominal wound dehiscence, and one case of pulmonary embolism. Morbidity was significantly associated with three clinical factors: male sex, high intraabdominal temperature during HIIC, and duration of the surgical procedure. Enteral complications (bowel fistula and anastomotic leak) occurred in patients with a significantly higher number of peritonectomy procedures and a significantly longer operation. Three patients died within 8 weeks after the procedure (mortality = 5%). Mortality was significantly associated with age and intraabdominal temperature. CONCLUSIONS: Cytoreductive surgery combined with HIIC is associated with a 35% morbidity rate and a 5% mortality rate. Extensive surgery (duration and number of peritonectomy procedures) and high intraabdominal temperature represent the major risk factors for postoperative morbidity and mortality of patients treated with this new therapeutic approach.

Adult↗
PubMed1996

Intraoperative hyperthermic lavage with cisplatin for peritoneal carcinomatosis and sarcomatosis.

Intraoperative hyperthermic lavage with cisplatin was studied in 8 patients with peritoneal carcinomatosis and sarcomatosis. A dose of 50 mg/m2 of cisplatin used for 2 hours with an intraperitoneal temperature of 41 degrees to 43 degrees C was used. Pharmacokinetic studies showed that cisplatin left the abdomen and pelvis by simple diffusion with a half life of 48 minutes in the peritoneal fluid. Eighty-six percent of the drug was absorbed into the plasma within 2 hours but only 6.9% was excreted into the urine. The area under the curve ratio for peritoneal fluid to plasma was 6.9. The quantity of cisplatin in tissue from the abdomen or pelvis was extremely variable. It was 1.85-10.28 micrograms cisplatin/g tumor and < 0.57-7.90 micrograms/g normal tissue. Comparison of pharmacologic parameters of hyperthermic to normothermic cisplatin administration showed no significant differences.

Antineoplastic Agents↗
PubMed1996

Surgically directed chemotherapy: heated intraperitoneal lavage with mitomycin C.

This chapter reported the pharmacokinetics and the toxicities of mitomycin-c (MMC) when administered as a hyperthermic intraperitoneal lavage after surgical resection of advanced primary or recurrent gastrointestinal cancer. Pharmacologic studies were performed in 10 patients and all adverse reactions were recorded in 20 patients. These 20 patients had advanced gastrointestinal malignancies with peritoneal carcinomatosis and underwent cytoreductive surgery prior to intraperitoneal lavage. Heated (42 degrees C) intraperitoneal mitomycin C was used in a lavage technique with 30 mg/3 1 of drug for 2 hours. The fluid was distributed throughout the abdominal cavity by vigorous external massage of the abdominal wall. This resulted in approximately 70 percent (21 mg) drug absorption from the perfusate. Urine output of MMC averaged 2.5 mg during the 2 hour procedure. Median peak blood levels of 0.25 micrograms/ml (range 0.11-0.41 micrograms/ml) were observed at 45-60 minutes into the procedure. Morbidity was low and was mainly related to the surgical procedures (prolonged ileus, postoperative fistulas) with mild to moderate drug-related myelosuppression. This new method of delivery of MMC and 5-FU should be explored in phase II clinical trials.

Adult↗
PubMed1996

Safety constiderations in the use of intraoperative intraperitoneal chemotherapy.

The clinical significance of occupational exposure to antineoplastic agents is controversial. Accrued evidence does not seem to indicate mutagenicity, carcinogenicity, and tertogenicity when exposure is limited by proper precautions. However, medical surveillance of personnel continually exposed to these cytotoxic agents will aid in early detection of any problems should they occur. Because the current fiscal milieu constantly emphasizes cost containment, true prevention means an intense worker education program. Personnel continually exposed to these cytotoxic agents should have scheduled health checkups twice a year, and exposure frequency should be reported to the employee's personal physician.

Antineoplastic Agents↗
PubMed1996

Hyperthermic intraoperative intraperitoneal chemotherapy safety considerations.

Perioperative staff members encounter many occupational exposure hazards in the workplace. Cytotoxic agent exposure is a relatively new hazard that perioperative staff members are experiencing as more surgeons use hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) to treat patients with abdominopelvic cavity malignancies. Routes of exposure include inhalation, ingestion, injection, and skin contact. The National Cancer Institute, the Occupational Safety and Health Administration, and the Joint Commission on Accreditation of Healthcare Organizations provide guidelines for the safe administration and handling of cytotoxic agents. Institutions in which cytotoxic agents are administered should use these guidelines to develop policies, procedures, and educational programs to protect surgical patients and perioperative staff members.

Abdominal Neoplasms↗
PubMed1995

Pharmacokinetic studies of intraaortic stop-flow infusion with 14C-labeled mitomycin C.

This pharmacokinetic study attempted to improve the exposure of gastrointestinal tract tissues to chemotherapy by increasing the transit time of a first pass of a drug through the vascular system. Bolus infusion of 9 mg mitomycin (MMC) mixed with 1 mg of MMC labeled by 50 microCi of 14C was performed in 18 mongrel dogs. Pharmacokinetics of MMC in peripheral, portal, and aortic blood were studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted a control group. In 15 dogs MMC was infused intraaortically with the catheter's tip at the level of the celiac and superior mesenteric artery. Vascular flow was controlled in four different ways for 30 min: Type I-Type IV. In Type IV the abdominal aorta and vena cava inferior were occluded after surgical exclusion of all nongastrointestinal branches of aorta. Blood samples were obtained during a 90-min period. After solubilizing the samples, 14C-labeled MMC activity was counted by a scintillation counter. For stop-flow infusion Type I, II, III, and IV, area under the curve (AUC) ratios for portal blood versus systemic circulation were 1.6:1, 2.9:1, 2.9:1, and 8.8:1, respectively (statistically significant for Types II, III, and IV). The highest value of AUC, peak MMC concentration, and lowest clearance in portal blood were achieved in SFI Type IV. Exposure to MMC was the greatest with SFI Type IV, making this type of aortic stop-flow infusion the most favorable mode of drug administration from a pharmacokinetic perspective.

Animals↗
PubMed1995

Cancer recurrence following laparoscopic colectomy. Report of two patients treated with heated intraperitoneal chemotherapy.

PURPOSE: Use of laparoscopic techniques for resection of colon and rectal cancer has raised considerable controversy. There is increasing concern that wound recurrence and peritoneal dissemination may represent a potentially fatal complication of this technique. METHODS: The surgical literature was reviewed, and clinical course of two patients is presented. RESULTS: Our two patients had tumor recurrence in the laparoscopy port sites within one year after laparoscopic assisted colectomy for Dukes B adenocarcinoma of the colon. At laparotomy, diffuse peritoneal carcinomatosis without lymph node or liver metastases were found in both patients. They were treated by surgical resection of recurrent disease combined with heated intraoperative intraperitoneal mitomycin C chemotherapy and five days of early postoperative intraperitoneal 5-fluorouracil. These patients are clinically free of disease at 1.5 years after treatment of peritoneal implants. CONCLUSIONS: Cancer recurrence in abdominal wall incisions after laparoscopic colectomy has been reported in an increasing number of patients. It is possible that this technique should be abandoned. Cytoreductive surgery combined with intraperitoneal chemotherapy may represent the most adequate treatment of recurrent cancer that occurs following laparoscopic colectomy.

Adenocarcinoma↗
PubMed1995

Intraaortic stop-flow infusion: pharmacokinetic feasibility study of regional chemotherapy for unresectable gastrointestinal cancers.

BACKGROUND: This study attempted to increase the exposure of gastrointestinal tract tissues to chemotherapy by prolonging the first pass of intraaortically administered drug by temporary occlusion of vascular structures. METHODS: Bolus infusion of 14C-labeled mitomycin C (MMC) mixed with unlabeled MMC was performed in dogs. Distribution of MMC in gastrointestinal tract tissues was studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted the control group. Vascular flow was controlled in four ways for 30 min: type I--stop-flow infusion (SFI) with clamping of the abdominal aorta above the celiac and below inferior mesenteric artery; type II--with additional clamping of the inferior vena cava above the diaphragm; type III with additional clamping of the portal vein in the hepatoduodenal ligament; and type IV--with surgical exclusion of nongastrointestinal branches of the aorta in addition to type II clamping. RESULTS: Type II and IV produced a 3-10-fold increase in exposure to MMC of major gastrointestinal tissues as compared with intravenous infusion. Area under the curve ratios with type IV were most prominent in the following tissues: stomach, pancreas, liver, and mesenteric lymph node. CONCLUSION: Access of MMC to several gastrointestinal tissues was increased through SFI. Type IV infusion was the most effective. Tissue exposure to MMC was especially advantageous for stomach, pancreas, liver, and mesenteric lymph node.

Animals↗
PubMed1993

False-positive lymph nodes by radioimmunoguided surgery: report of a patient and analysis of the problem.

Preoperative administration of radiolabeled monoclonal antibody allows radioimmunoguided surgery with hand-held intraoperative detection devices. From a theoretical perspective, this technology may offer more knowledgable patient management and more complete resection of intra-abdominal cancer. False-positive examinations may seriously jeopardize the widespread application of this apparatus. Our experience with a patient with false-positive lymph nodes following administration of 125I-labeled B72.3 monoclonal antibody is reported. After careful histopathological analysis of five nodes thought to be false-positive for cystadenocarcinoma, one lymph node was found to have a minute nidus of cancer. The cause of false-positive radioimmunoguided tests and their implications for the clinical use of this tool is discussed. We interpreted our data to suggest that tumor antigen-monoclonal antibody complexes processed in reactive lymph nodes, anatomically draining the malignant tissue, may cause false-positive tests.

Adult↗
PubMed1992

Enhanced platelet reactivity and hypercoagulability in the steady state of sickle cell anaemia.

A prospective controlled study was undertaken to investigate the haemostatic and coagulation status of 18 adult subjects in the steady state of sickle cell anaemia (SCA), using a relatively new in vitro technique. Shear induced haemostasis, whole blood dynamic coagulation, and spontaneous thrombolysis were measured using nonanticoagulated blood. As expected, the haemoglobin levels were significantly lower and platelet counts significantly higher in subjects with SCA compared with controls. Haemostasis and coagulation were significantly enhanced in SCA. No correlation was found between the raised platelet count and enhanced haemostasis or the reduced haemoglobin and hypercoagulation, respectively. Hyperactivity of the haemostatic system may have a pathogenic role in vaso-occlusive microthrombotic events and in the leg ulcers, both of which occur frequently in SCA.

Adolescent↗
PubMed1989

Cystinuria and its treatment: 25 years experience at St. Bartholomew's Hospital.

Cystinuria is an inherited condition affecting the active transport of the diamino acids cystine, ornithine, lysine and arginine across the renal tubule and the small intestine. The only clinical effect is the production of urinary tract stones and if these can be prevented the affected individuals can lead a normal life. In many people cystine stones can be dissolved and new stone formation prevented by a high fluid intake, but if this does not succeed regular treatment with penicillamine will do so. Although many side-effects have been described with penicillamine treatment it is rare for them to be severe enough to prevent its use in patients with cystinuria. Since the clinical effects of cystinuria can be prevented by either a high fluid intake or by penicillamine it is important to make the diagnosis in affected individuals as soon as possible and cystinuria should therefore be considered in all people (regardless of age) who form urinary stones.

Cystinuria↗