Biomedical subjects

D F Devereux

Publications and source records attributed to D F Devereux.

At least 19 recordsLinked to original sources

PubMed1992

Experience with high-dose radiation therapy and the intestinal sling procedure in patients with rectal carcinoma.

BACKGROUND: Surgery for Dukes' Stage B2 or C rectal carcinoma has a locoregional recurrence rate of 15-67%; this rate is significantly reduced when postoperative radiation therapy (RT) is given. However, RT contributes to radiation-associated small bowel injury in a dose-dependent manner. METHODS: Polyglycolic acid mesh used as an intestinal sling is able to keep the small bowel out of the pelvis during RT, thereby preventing radiation-associated small bowel injury. RESULTS: The authors reviewed the perioperative experiences and acute toxic effects of RT in 53 patients in whom the polyglycolic sling was placed from May 1985 through May 1990 during laparotomy for rectal malignancies (47 primary and 6 recurrent). There were 26 men and 27 women whose ages ranged from 34 to 88 years (mean, 64.7 years). Mild postoperative ileus occurred in most patients, and one patient had an anastomotic leak with a pelvic abscess. Bowel displacement from RT portals was confirmed using radiologic contrast studies. Forty-three patients with primary tumors have completed postoperative RT, and a mean of 5174 cGy has been administered. CONCLUSIONS: After 1-6 years of follow-up (mean, 2.1 years), eight patients have died of systemic disease. There were no cases of radiation-associated small bowel injury and only two cases of pelvic recurrence from primary rectal adenocarcinoma (5%).

Adult↗

PubMed1992

Identification of a human tumor-derived lipolysis-promoting factor.

Our previous studies have demonstrated the production and release of a tumor-derived factor that promoted lipolysis in normal adipocytes. We further demonstrated that this in vitro lipolysis was correlated with the in vivo loss of total carcass lipids induced by the presence of the same tumor. This study identified and isolated this "lipolysis-promoting" factor (LPF), released into the extracellular environment (conditioned media) by the human A375 melanoma cell line, which appears to be responsible for the previously demonstrated induction of in vitro and in vivo lipolytic activity. Unlike previously described non-tumor-derived molecules, such as tumor necrosis factor-alpha/cachectin, which have been implicated in cancer cachexia, the LPF induces alterations in lipid metabolism similar to those observed in cancer patients. The biochemical nature of human tumor-derived LPF appears to be a heat-stable molecule with an apparent molecular weight of approximately 6000. The lipolysis-promoting activity was trichloroacetic acid precipitable, but not precipitable with protamine sulfate or extractable with chloroform:methanol. Its activity appears to be resistant to enzymatic treatments with protease K, trypsin, Pronase, RNase, and DNase, as well as to periodate oxidation. Immunochemically, LPF appears to be distinct from tumor necrosis factor-alpha/cachectin. Furthermore, in contrast to the mechanism of action of tumor necrosis factor-alpha/cachectin, the mechanism of "lipolysis promotion" by LPF appears to be by the induction of cellular lipase activity.

Adipose Tissue↗

PubMed1992

Treatment of hepatic metastases from colorectal origin.

Currently, chemotherapy for hepatic metastatic disease is palliative at best. However, successful resection of hepatic metastatic deposits from colorectal origin demonstrates a five-year survival, approaching 60 percent in selected cases.

Clinical Protocols↗

PubMed1991

The effects of doxorubicin and mitoxantrone on wound healing.

The goal of the present study was to determine whether mitoxantrone would impair wound healing to a similar degree as doxorubicin when given in equally cytotoxic doses. On day 0, male Fischer rats were wounded and treated with 5% dextrose (control), 6 mg/kg doxorubicin, or 1.2 or 2.4 mg/kg mitoxantrone. On day 5, WBCs for the doxorubicin group and the group that had been treated with 1.2 mg/kg mitoxantrone were 33% and 43% lower than control values, respectively. All rats that had been given 2.4 mg/kg mitoxantrone died within 1 week of being wounded due to drug toxicity. On day 21, wound-breaking strength (WBS) analysis was performed: two skin specimens were taken from each dorsal skin incision perpendicular to the scar axis and were subjected to wound disruption (grams of force) by uniaxial extension. The WBS analysis indicated significant differences between the doxorubicin treated group (1183 +/- 96 g) and the control group (2422 +/- 247 g). However, no significant difference was found between the group that had been given 1.2 mg/kg mitoxantrone (2140 +/- 191 g) and control animals. Thus, mitoxantrone seems to exert myelosuppressive effects similar to those displayed by doxorubicin, but the former drug results in significantly less impairment of wound healing in the rat model.

Animals↗

PubMed1991

Peritoneal leukocyte response following placement of polyglycolic acid intestinal sling in patients with rectal carcinoma.

The intestinal sling procedure has been used successfully without the observance of pelvic infections. This procedure involves the implantation of polyglycolic acid (PGA) mesh to hold the bowel out of the pelvis to prevent radiation enteritis. We previously showed that PGA mesh has no intrinsic bactericidal activity. Since phagocytic leukocytes produce reactive oxygen intermediates during respiratory burst that are associated with oxygen-dependent bactericidal activity, we examined peritoneal cell types and their respiratory burst activity isolated from patients with biopsy-confirmed rectal carcinoma who underwent the intestinal sling procedure (N = 12) compared with patients who did not (N = 13). There was no significant difference in the cell types within the peritoneal cavity over the 7-day postoperative period examined. However, there was a significant increase in the ability of leukocytes isolated from mesh patients to produce hydrogen peroxide in the absence of an exogenous stimulus (P less than 0.05), as measured by flow cytometric quantitation of oxidation of the hydroperoxide-sensitive dye, 2',7'-dichlorofluorescin diacetate (DCFH-DA). Despite the higher endogenous DCFH oxidation by leukocytes from mesh patients, the cells retained the ability to oxidize DCFH following treatment with a membrane-active stimulant for respiratory burst activity, 12-O-tetradecanoyl-phorbol-13-acetate. These observations suggest that PGA mesh used for the intestinal sling procedure stimulates the respiratory burst activity of peritoneal leukocytes during the postoperative period in which bacterial proliferation and colonization occur. The stimulation of reactive oxygen intermediates involved in oxygen-dependent bactericidal activity by PGA mesh may be one of the mechanisms underlying the lack of infections observed with the use of PGA mesh in contaminated settings.

Bacterial Infections↗

PubMed1991

Induction of leukocyte activation by meshes surgically implanted in the peritoneal cavity.

The search for surgical prosthetics that do not act to promote infection has been frustrating. However, recent experience with the implantation of polyglycolic acid mesh (PGA) used as an intestinal sling has been associated with a lack of pelvic infections. To examine the basis for these observations, 1 x 1-cm pieces of biomaterials were sewn onto the peritoneal cavity of rats. The biomaterials examined included PGA mesh, a composite mesh composed of a permanent nonabsorbable Novafil inner layer coated with a PGA outer layer, polyvinyl alcohol sponge, and silicon elastomer. Biomaterials were removed at postoperative days 1, 2, 8, and 14, and examined for bacteriostatic and bactericidal activity by standard techniques. Mesh adherent leukocytes were evaluated for their ability to oxidize dichlorofluorescein diacetate (DCFH-DA), which is fluorescent in the presence of intracellular hydrogen peroxide produced by both polymorphonuclear cells and monocytes. PGA and the composite mesh had no intrinsic bacteriostatic or bactericidal activity. However, adherent leukocytes were induced to oxidize DCFH at levels 10-fold and 5-fold, respectively, by postoperative day 14, compared with earlier time points and other biomaterials. The ability of these PGA meshes to stimulate respiratory bursts by peritoneal cells may partly be responsible for the lack of infections associated with their use.

Animals↗

PubMed1990

The effect of interleukin-2 administration on wound healing in adriamycin-treated rats.

Adriamycin (doxorubicin hydrochloride), an effective chemotherapeutic drug, is also a potent inhibitor of wound healing. Conversely, certain polypeptide growth factors are capable of stimulating fibroblasts to secrete collagen, thus enhancing wound healing. The purpose of this study was to determine if interleukin-2 (IL-2), a T-cell growth factor, could reverse the wound healing deficit caused by Adriamycin. Adriamycin treatment caused a significant decrease in wound-breaking strength (P less than 0.005). IL-2 administration increased wound-breaking strength in Adriamycin-treated animals (2126 g vs 1549 g, P less than 0.005). In control animals, IL-2 did not increase wound-breaking strength significantly (2708 g vs 2608 g, P greater than 0.1). Histologically, wounds from Adriamycin-treated animals were less cellular, demonstrated less collagen in the dermis, and a lesser degree of capillary ingrowth. The number of fibroblasts in the dermal layer was increased in animals receiving IL-2. Control rats gained an average of 1.4% of their original body weight, while Adriamycin-treated rats lost an average of 19% of their original body weight (P less than 0.0005). IL-2 administration did not influence weight loss or gain. Hematologically, animals receiving Adriamycin had lower hemoglobin and hematocrit values and higher platelet counts. There were no differences in total white blood cell counts; however, animals receiving Adriamycin showed a predominance of polymorphonuclear leukocytes and a relative decrease in lymphocytes. Animals receiving IL-2 demonstrated a significant eosinophilia. (1) Adriamycin impairs normal wound healing. (2) Interleukin-2 administration improves the wound healing impairment caused by Adriamycin. (3) Interleukin-2 appears to increase infiltration of inflammatory cells, fibroblasts, and capillaries into the wound, which may account for the observed increase in wound breaking strength.

Animals↗

PubMed1990

Diagnosis and management of dysplastic nevus syndrome and early melanoma.

Malignant melanoma may arise de novo as well as in association with pre-existing dysplastic nevi. The latter serve as markers, since people who have them are at a higher risk for the development of malignant melanoma than is the general population. Patients with the syndrome should be examined carefully, including the scalp and eyes, every three to six months. Suspicious nevi should be photographed and biopsied, and a family history taken. Excision of dysplastic nevi may be indicated in patients with a positive family history for malignant melanoma, due to the high risk of developing a cutaneous melanoma. We need to educate patients regarding the need for continued follow-up, self-examination, and avoidance of sun exposure.

Dysplastic Nevus Syndrome↗

PubMed1990

Effects of method of hemostasis on wound-infection rate.

Adequate hemostasis is important in preventing postoperative wound infection. This study compared four methods of hemostasis: specific pinpoint vessel electrocautery (SPC), specific vessel ligation with 4-0 vicryl (SVL), nonspecific electrocautery of vessel plus excessive surrounding tissue (NSC), and nonspecific ligation of vessel and excessive surrounding tissue with 4-0 vicryl (NSL), on the rate of wound infection in rabbits that were contaminated with 10(6) Staphylococcus aureus. There was no statistical significant increase in the rate of wound sepsis when electrocautery was used in a fashion producing minimal nonviable tissue compared to specific vessel ligation. Electrocautery use for specific vessel hemostasis does not result in a higher wound infection rate in contaminated wounds.

Animals↗

PubMed1989

The safe and effective use of postoperative radiation therapy in modified Astler Coller Stage C3 rectal cancer.

Locoregional recurrence in patients with Stage C3 (adjacent organ invasion) rectal carcinoma approaches 100% when surgery is not followed by adjuvant radiation therapy. The advent of the intestinal sling procedure (use of an absorbable polyglycolic acid mesh to suspend the small bowel out of the pelvis) has allowed tumoricidal doses (5000 cGy) of radiation therapy to be delivered to the pelvis without incurring radiation associated small bowel injury (RASBI). This surgical technique has allowed us to readdress the question, "what is the effectiveness of postoperative radiation therapy when tumoricidal doses can be safely administered to patients with Stage C3 rectal cancer?" Nineteen consecutive patients with Stage C3 rectal carcinoma underwent resective procedures and simultaneous use of the intestinal sling procedure. Postoperatively, all patients underwent contrast simulation studies that documented the small bowel above the sacral promentory. Tumoricidal doses ranging from 5200 to 5800 cGy (mean, 5600 cGy) were administered in fractionated doses. No patient demonstrated obstruction, infection, nausea, vomiting, cramps, diarrhea, or acute RASBI. There have been two locoregional recurrences in a mean follow-up period of 33 months (range, 12 to 54 months) in patients evaluated by physical examination, carcinoembryonic antigen (CEA) levels, computed axial tomography (CAT) scans, endoscopy, and reoperation or autopsy (P = 0.01). There have been ten distant recurrences (eight liver, one brain, and one lung). Three patients were reoperated on to rule out recurrence at 16, 17, and 24 months. All mesh was resorbed and there were no adhesions and no recurrent tumor. When the intestinal sling procedure is used, tumoricidal doses of radiation therapy can be safely administered without incurring RASBI. Postoperative high-dose radiation therapy can suppress locoregional recurrences in Stage C3 rectal carcinomas over and above what would be expected.

Aged↗

PubMed1989

Melanoma-pigmented lesion center.

Early diagnosis of cutaneous malignant melanoma is of critical importance as thin lesions equate with increased survival. Detection has been made easier by the development of a computer-programmed, high-resolution camera capable of detecting changes in surface area as well as low-level color changes, which are associated with radial (noninvasive) growth.

Cell Transformation, Neoplastic↗

PubMed1988

Efficacy of an absorbable mesh in keeping the small bowel out of the human pelvis following surgery.

Patients with pelvic malignancies frequently require postoperative radiation therapy either as adjunctive or palliative treatment. Tumoricidal doses, however, are frequently associated with small-bowel damage. Animal experiments demonstrated tolerance to high-dose radiation therapy and protection from radiation enteritis by use of an absorbable polymer polyglycolic acid (PGA) that is used as an intestinal sling to elevate the small bowel away from the operated site. Sixty patients (42 with rectal carcinomas and 18 with gynecologic malignancies) underwent surgical treatment that included the intestinal sling procedure. Postoperative radiation was begun within three weeks following surgery and patients received a mean approximating 5500 rads in fractionated doses. A mean follow-up time of 28 months has not revealed a single case of radiation enteritis (by either contrast studies or physiologic studies) or PGA mesh-related complications. The authors believe that this surgical technique should be employed in patients who may require postoperative radiation treatment for pelvic malignancy.

Combined Modality Therapy↗

PubMed1988

New surgical method to prevent pelvic radiation enteropathy.

Pelvic radiation doses exceeding 4,000-4,500 cGy are known to be associated with acute and chronic radiation enteropathy. This same radiation dose is, at the same time, only moderately effective in the elimination of microscopic malignancy, let alone gross clinical disease. Numerous medical and surgical attempts to minimize this complication have been uniformly unsuccessful. With the availability of a new synthetic, absorbable, polyglycolic acid mesh, an intestinal sling surgical procedure has been devised to exclude the small bowel from the pelvis and subsequent radiation fields. Twenty-five patients have been treated by this new technique with only one complication presenting as a fungal infection. Small-bowel barium contrast studies in 16 patients referred for postoperative radiation demonstrated 13 satisfactory exclusions of the small bowel from the translateral pelvic irradiation field. In 16 evaluable patients, three had unsatisfactory exclusion two of which were due to technical error. This has permitted high-dose (5,500-6,500 cGy) radiotherapy to the critical treatment volume without posttreatment complication. Mean follow-up time is 14.8 months. Several patients have been reexplored demonstrating complete absorption of the mesh without fibrinous adhesions or other foreign body reaction. It is concluded that this new technique of small bowel exclusion will permit the routine delivery of much higher doses of radiation in patients requiring improved local-regional control of their pelvic cancers and without morbidity from radiation-associated small bowel injury.

Aged↗

PubMed1987

Pyloric exclusion. Suture material of choice.

Pyloric exclusion was first reported in 1977 as a temporary method of providing duodenal decompression in an attempt to protect the duodenum in the early postoperative period during the healing phase, followed by the return of normal gastrointestinal transit. It has been adopted by several trauma centers across the country as part of their armamentarium for managing moderate to severe duodenal injuries. Most series report using a polyglycolic acid (PGA) suture in performing the exclusion, anticipating a 3- to 4-week interval before pyloric patency is re-established. A comparison of polypropylene (PP), polyglycolic acid (PGA), and polydioxanone (PDS) sutures in the dog model suggests, however, that only PDS reliably accomplishes this goal. The low (approximately 5-10%) but finite incidence of fistula formation reported with pyloric exclusion using PGA may be improved by using PDS instead.

Animals↗

PubMed1987

Successful treatment of stages IIIa and IIIb carcinoma of the breast by mastectomy in the elderly high risk patient using local anesthesia.

Modified radical mastectomy has served as the standard surgical treatment for patients with operable carcinoma of the breast. Recent data suggest that lumpectomy combined with radiation therapy is adequate treatment for smaller carcinomas of the breast. However, large carcinomas of the breast may still require a modified radical mastectomy for adequate local treatment or until lesser procedures are proved sufficient. This study was done to describe the use of local anesthesia and modified radical mastectomy (with sparing of the pectoralis minor muscle) in 17 patients who were considered a poor risk for general anesthesia and had Stages IIIa and IIIb carcinomas of the breast. Patient acceptance was excellent in 14, moderate in two and poor in one patient. Blood loss never exceeded 75 milliliters and a mean of 120 milligrams of Xylocaine (lidocaine) was used. No apparent central nervous system toxicity was observed. Mean time on the surgical service was 2.7 days. Modified radical mastectomy can be successfully accomplished in patients considered a "poor risk" for general anesthesia and with locally advanced carcinoma of the breast using local anesthesia with minimal blood loss and excellent patient acceptance.

Aged↗

PubMed1987

Effects of retinoic acid on lipolytic activity of tumor cells.

Tumor-producing substances that promote lipolysis in vitro may also account for fat mobilization in cachectic cancer patients. Cachexia might improve if this lipolytic action of cancer cells could be halted. This study examined the lipolytic activities of media from four tumor cell lines after treatment with retinoic acid (RA), a cell differentiation inducer. An in vitro adipocyte bioassay measured lipolysis. All four tumor cell lines were intrinsically lipolytic, with elevated baseline lipolytic activities relative to fibroblast-conditioned controls (128% to 287% of control, p less than 0.05). After a 2-week exposure to RA in culture medium followed by 3 days of continued growth in fresh medium, two of four cell lines (both rat prostatic adenocarcinomas) showed significantly reduced lipolytic activities (16% and 61% of corresponding untreated controls, p less than 0.05). These reductions in lipolytic activity after RA treatment were not generalized phenomena; nor were they simply caused by cell differentiation, as the other cell lines (human malignant melanoma and human ovarian teratocarcinoma) showed no reductions despite evidence of cell differentiation. No effect on lipolytic activity was seen after only a 24-hour exposure to RA. We conclude that RA can affect the lipolytic activity of certain tumor cells in vitro, perhaps by influencing tumor-producing lipolytic factor(s).

Adenocarcinoma↗

PubMed1987

Protection from radiation enteritis by an absorbable polyglycolic acid mesh sling.

Patients with malignant tumors of the pelvis who cannot be cured surgically often are treated with radiation after surgery. A devastating side effect of this treatment is radiation-associated small bowel injury (RASBI). The purpose of this study was to test the hypothesis that removal of the small bowel from the radiation field would protect it against RASBI. Twenty cebus monkeys underwent low anterior resection. In 10 animals an absorbable polyglycolic acid (PGA) mesh was sewn circumferentially around the interior of the abdominal cavity as a supporting apron, which prevented the small bowel's descent into the pelvis. The other 10 monkeys did not receive the mesh. All animals received 2000 rads by linear acceleration in a single dose. Twenty-four-hour stool fat, serum vitamin B12, and other serum values were obtained during the study. Animals were sacrificed after 1, 2, 3, 6, and 12 months, and the small bowel and rectum were examined histologically in a blind manner. Two monkeys who did not undergo surgery, or exposure to radiation served as controls. At all sacrifice periods, the animals with PGA mesh slings demonstrated normal small bowel function and histologic structure. Animals without mesh slings had abnormal stool and blood values at 1 month, and by 2 months all had died of small bowel necrosis. The animals that received the slings had no evidence of infection or obstruction, and by 6 months all evidence of the mesh was gone. Support of the small bowel out of the pelvis by an absorbable PGA mesh sling protects against RASBI and is without apparent complications.

Animals↗

PubMed1987

Effects of tumor bearing and removal on blood levels of lipids, lipolytic activity, and glycerol and on carcass weight in the rat.

In this animal model we investigated the effects of sarcoma bearing and complete or incomplete tumor excision on blood levels of lipids, lipolytic activity, and glycerol and on carcass weight. We also sought causes that could account for the apparent increase in lipid mobilization. Tumor-bearing (TB) rats had depleted retroperitoneal fat stores, elevated blood triglycerides and cholesterol, and normal thyroid, hepatic, and renal function during tumor bearing. Catecholamine, growth hormone, and glucagon levels were not different between TB and nontumor-bearing (NTB) groups. Serum lipolytic activity and glycerol levels, which were elevated during tumor bearing, returned to NTB levels after complete tumor excision, along with restoration of retroperitoneal fat depots and carcass weight. The elevated serum lipolytic activity of animals that had tumors only incompletely excised rose significantly higher after the tumor regrew; this was accompanied by a failure to regain carcass weight. Previous work has shown that elevated lipolytic activity can also be demonstrated in culture media conditioned by growth of certain animal or human tumor cell lines in cell culture, free of host influences. This suggests that the actual tumor cell and not the host may be at least partly responsible for the lipid derangements seen in this model.

Animals↗