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Biomedical subjects

W P Reed

Publications and source records attributed to W P Reed.

At least 19 recordsLinked to original sources

Laparoscopic screening of surgical candidates with pancreatic cancer or liver tumors.

BACKGROUND: Patients with colorectal or pancreatic cancers may have peritoneal implants which are too small to be detected by current radiologic imaging techniques. Since such implants often preclude surgical removal of the primary tumor or isolated metastasis, their detection prior to open abdominal exploration may spare patients the morbidity of a large abdominal incision when there is no benefit to resection and lifespan is limited. METHODS: In the past 30 months, patients with pancreatic cancer, hepatoma, or isolated colorectal cancer metastases, who were candidates for surgical resection on the basis of standard radiologic scans, were examined with the laparoscope through a 10-mm periumbilical incision prior to undertaking open abdominal exploration. If unexpected implants were noted, biopsy was obtained through a 5-mm port placed through a convenient site. RESULTS: Since January 1993, 11 patients with pancreatic carcinoma, three patients with primary hepatic malignancies, and 12 patients with isolated metastases from colorectal cancers have undergone laparoscopic examination prior to celiotomy. Eight of these patients had unexpected peritoneal or liver involvement which precluded resection. Laparoscopy was successful in detecting disease in six such patients (75%). CONCLUSION: Although adding 20-30 min to the operative time when unrevealing, laparoscopy provided an effective way to avoid celiotomy in patients with carcinomatosis.

Colorectal Neoplasms

[10 year results of preoperative radiotherapy in treatment of rectal carcinoma].

BACKGROUND: We have previously reported improvements in survival and disease-free survival at five years using preoperative radiation in the treatment of rectal cancer. The current update was undertaken to determine if these favorable results were durable with longer follow-up. METHODS: Patients found to have resectable rectal cancer between 1972 and 1979 were treated with 40-45 Gy of preoperative radiation (40 patients) or resection alone (109 patients). Follow-up information beyond five years was obtained from the Tumor Registry, physician contact and a survey of the National Death Index. Of the 149 patients followed for five years, 144 were evaluable at ten years. RESULTS: After a median follow-up of 125 months, survival of the irradiated patients was significantly better than that of controls (77 versus 57% at 5 years and 74 versus 41% at 10 years, p = 0.0044). Disease-free survival of those patients whose resection margins were free was also superior for the irradiated group (85 versus 59% at 5 years and 80 versus 45% at 10 years, p = 0.0045). CONCLUSIONS: The results show that the survival advantage for 40 to 45 Gy preoperative radiation in the treatment of rectal cancer persist at 10 years follow-up.

Cobalt Radioisotopes

The influence of local tumor ulceration on the effectiveness of endocavitary radiation for patients with early rectal carcinoma.

BACKGROUND: Endocavitary radiation therapy is an alternative to surgical therapy for some early rectal carcinomas. Careful patient selection is necessary to ensure good results. The purpose of this study was to examine the authors' experience with endocavitary radiation at their institution from 1984 to 1991 to determine which factors were associated with treatment failure to provide for better future patient selection. METHODS: Thirty-two patients with carcinoma of the rectum, not apparently involving the muscle wall, underwent 75-120 Gy of endocavitary radiation as potentially curative therapy. Treatment was given as a series of 2-4 doses of 30 Gy at three weekly intervals. Twenty-two patients had polypoid tumors, 5 sessile, and 5 ulcerated. RESULTS: After a mean follow-up of 43 months (range, 6-103 months), 4 of 5 patients (80%) with ulcerated tumors developed local recurrences, compared with only 4 of 27 (15%) with sessile or polypoid lesions. Not only was the incidence of local recurrence greater for patients with ulcerated tumors (P = 0.009), but the time to recurrence was shorter also (P = 0.0001). Tumor size, anterior or posterior location, and dose of radiation received did not affect the rate of recurrence. CONCLUSIONS: These results indicate that superficial polypoid and sessile rectal tumors can be managed successfully with endocavitary radiation. Ulcerating tumors are likely to recur locally within a short time and therefore should be considered for surgical treatment initially.

Aged

Streptococcal adherence to Langerhans cells: a possible step in the pathogenesis of streptococcal pharyngitis.

Group A streptococci are nonmotile and have no structures that would enable them to penetrate submucosally into the pharynx. We have postulated that they adhere to host pharyngeal mucosal cells called Langerhans cells that are motile and could transport them into deeper tissues. We used a microscopic assay to assess the adherence of streptococci to cells from normal pharyngeal scrapings after the cells and bacteria were incubated in vitro. Langerhans cells were identified by immunofluorescent staining for the CD1a antigen. Nonstaining cells were considered to be keratinocytes. Of the 2279 cells examined from 9 subjects, 92.6% were keratinocytes and 7.4% were Langerhans cells. Only 1.8% of the 2111 keratinocytes had > 50 bacteria attached in this assay, while 76.2% of the 168 Langerhans cells had > 50 attached bacteria. Thus, under the conditions of this study, group A streptococci adhere preferentially to Langerhans cells from the pharynx. Adherence to these motile cells may provide a mechanism through which pathogenic streptococci may be transported into submucosal tissues.

Adult

Evaluation of gastrointestinal hemorrhage in patients with neurofibromatosis.

Over a 3-year period, two patients with neurofibromatosis were referred to our medical center for evaluation of repeated episodes of melena. Upper endoscopy was unrevealing in each case, as was colonoscopy. Arteriography during active hemorrhage was helpful in localizing the source of bleeding in one patient but not in the other. The source of bleeding in each patient was obvious at surgical exploration. Large neurofibromas protruded from the serosal surface of a short region of jejunum in both cases and an additional segment of ileum in one case. Hemorrhage had occurred as a result of erosion of mucosa stretched over these tumors. Local resection of the involved segments produced long-term control of the hemorrhage. Since these tumors were grossly visible on the serosal surface of the involved intestinal segments, laparoscopic evaluation could have been used to hasten diagnosis in each case.

Adult

Preceptored introduction of laparoscopic techniques for cholecystectomy into a large university-affiliated medical center.

Faced with the task of introducing laparoscopic techniques for cholecystectomy into the practice of a large department composed of individuals with varied backgrounds and experience, our surgical staff decided to grant provisional provileges to five surgeons, two from the full-time faculty and three from the community, who had completed a formal course in laparoscopic cholecystectomy. These five surgeons agreed to assist one another through 10 cases a piece before performing any procedures on their own or serving as preceptors for additional surgeons. Other surgeons could obtain credentials for this procedure by satisfying the same course criteria and receiving assistance from one of the five original surgeons during their first 10 cases. In the 14 months after September 1990, 250 laparoscopic cholecystectomies were performed by 19 different attending surgeons at our hospital. One death from hemorrhage (0.4%) and two bile duct injuries (0.8%) occurred in these patients. One of the bile duct injuries occurred after conversion to open cholecystectomy, as did the hemorrhage, which was from a vessel within the parenchyma of the gallbladder bed which rebled even after temporary control through open ligature technique. The second bile duct injury, the result of injudicious application of hemoclips for hemostasis, was minor in degree and the only injury to occur in a procedure conducted exclusively through the laparoscope. This experience demonstrates that laparoscopic techniques can be safely introduced into an environment involving multiple surgeons by adherence to a careful protocol of preceptored assistance.

Academic Medical Centers

Hickman catheters in association with intensive cancer chemotherapy.

Hickman catheters were the major venous access devices utilized at the University of Maryland Cancer Center from November 1978 to 1987. This study provided an opportunity to standardize insertion technique, to manage catheter-related activities and daily maintenance procedures in order to examine the progression of Hickman-catheter-related problems, to identify those factors that may minimize them, and to develop guidelines for the management and prevention of complications and malfunctions. In all, 690 Hickman catheters (368 double lumens) were placed in patients with acute leukemia and other cancers: 401 catheters were placed in patients with leukemia; 269 were placed during neutropenia; and 230 at platelet counts of < 50,000/microliters. Two surgeons inserted 490 catheters, and the remaining 200 were placed by a group of rotating surgeons. All catheters were placed with the intention that they would remain in place as long as clinically necessary. Total Hickman catheter days were 134273. Infectious complications included exit site infections (160), tunnel infections (46) and bacteremias (397). There were 438 instances of noninfectious complications including thrombosis, lack of function, catheter migration, fracture and hemorrhage. Recommendations for prevention and treatment of Hickman-catheter-related complications include the development of a select group committed to placement, daily maintenance and management of problems; prompt removal of catheters with Candida sp. fungemia and bacteremia due to Bacillus sp. or a bacteremia that persists for > 48 h after initiation of appropriate antibiotics, tunnel infections or Hickman-catheter-associated thrombosis. The majority of bacteremias and exit site infections can be effectively treated with antibiotics and local care.

Acute Disease

Neutrophil responses to intravascular pneumococcal sonicate.

Leukopenia and pulmonary leukostasis are prominent features in patients succumbing to pneumococcal (PNC) infections. We examined mechanisms involved in recruitment of polymorphonuclear neutrophils (PMNs) into pulmonary capillaries and alveolae after PNC sonicate injection. We showed that by 15 min postinjection, PMN chemotactic activity was found in bronchoalveolar lavage (BAL) fluids and increased with time until the end point of the study at 90 min. Accompanying the increased chemotactic activity in BAL fluids was a decrease in circulating PMNs more pronounced in the femoral artery (FA) than the pulmonary artery (PA). Superoxide anion (O2-) production by peripheral PMNs was depressed following PNC sonicate injection, and comparison of FA and PA showed that FA PMNs produced less O2- than PA PMNs. PA PMNs also showed enhanced random migration when compared to the depressed random migration of FA PMNs. This study demonstrated that an intravascular challenge of PNC sonicate was associated with increased chemotactic activity for PMNs in BAL fluid. Fewer PMNs and altered PMN function resulted from passage through the pulmonary microvasculature after PNC sonicate injection.

Animals

Hip disarticulation for recurrent vulvar cancer in the groin.

A patient with squamous cell carcinoma of the vulva treated with a radical vulvectomy and bilateral inguinal and femoral lymphadenectomies utilizing separate groin incisions, subsequently developed a recurrence in the skin bridge between the vulvar and groin excisions. Following groin irradiation with chemosensitization, the tumor progressed to involve the superior public ramus and femoral vessels. A left hip disarticulation and resection of a portion of the superior pubic ramus was performed. The patient has been free of disease for 3 years. The advantages of this procedure over a hemipelvectomy include shorter operative time, reduced blood loss, better fascial closure of the abdomen, and the creation of a stump which is more amendable to prosthetic fitting.

Carcinoma, Squamous Cell

Differences in blood group B-specific mucinase activity between virulent and avirulent Shigella flexneri 2a strains.

Based on our previous findings we postulate that the production of blood group B-degrading mucinase by Shigella flexneri 2a is related to virulence. The virulent S. flexneri 2a strain M4243 produced a blood group B mucinase which decreased the blood group B reactivity of germ-free mouse mucins by a factor of 16 and the B reactivity of human saliva by a factor of 32. Avirulent S. flexneri 2a B-1, serologically similar, but not genetically identical to the M4243 strain, failed to degrade the blood group reactivity. The mucin-degrading ability of S. flexneri 2a M4243 harboring a large virulence-conferring 140 MDa plasmid was then compared with a genetically similar large plasmid-free avirulent S. flexneri 2a M4243A1. Virulent S. flexneri M4243 grew in human salivary mucins while the genetically identical avirulent M4243A1 did not. Supernatant of virulent M4243 culture decreased the blood B reactivity of salivary mucins by a factor of 32 while the avirulent M4243a1 had no effect. Eleven of 12 colonies of the transconjugant hybrid Escherichia coli K12 (7300-1-5) containing the shigella PWR 110 plasmid and chromosomal markers decreased the blood group B reactivity by a factor of 4-32, and two of four colonies of the E. coli strain 7262 containing only the plasmid reduced the B reactivity by a factor of 4-16. These findings suggest that blood group B-specific mucinase production may be related to S. flexneri virulence.

ABO Blood-Group System

Intravenous access devices for supportive care of patients with cancer.

Reliable long-term venous access is crucial as a pathway for the delivery of many current chemotherapeutic agents, as well as for the supportive measures needed to sustain patients during their recovery from the toxic effects of these drugs. Many access devices are now available, but all carry the risk of infection, thrombosis, and complications related to their insertion. Recent advances in technology and the use of antibiotics and anticoagulants offer the opportunity to reduce the rate of many of these complications.

Antineoplastic Agents

The accuracy of malignant diagnoses established by fine needle aspiration cytologic procedures of mammary masses.

Fine needle aspiration cytologic studies are being used with increasing frequency to diagnose carcinoma of the breast. To determine whether or not a diagnosis of carcinoma established by cytologic examination is sufficiently accurate to proceed to treatment without tissue confirmation, we have examined our results in a series of 109 patients who had 111 aspiration cytologic procedures followed by open biopsy between January 1985 and June 1987. From this group, 39 specimens were read as malignant and 19 were read as suspicious. Thirty-eight of 39 specimens with positive readings were from lesions that proved to be malignant on subsequent open biopsy. Seventeen of 19 suspicious specimens were also from malignant lesions. Three of 17 specimens that were inadequate and nine of 36 negative specimens were from lesions that were later shown to be malignant. Our single false-positive result occurred on cells that had been air dried during preparation in the early months of experience with this technique at our institution. Re-evaluated later in our series, the same specimen was called suspicious rather than malignant. We conclude that a positive reading on fine needle aspiration is highly accurate. The positive predictive value should be 100 per cent, once experience is gained in preparing and interpreting the material. Open biopsy is necessary for inadequate, negative or suspicious specimens to exclude a malignant lesion if the clinical or mammographic findings are consistent with carcinoma.

Adolescent

Correlation between mammography and the pathology of nonpalpable breast lesions.

One hundred consecutive needle localization biopsies were performed for nonpalpable breast lesions discovered on low-dose mammography of asymptomatic women between June, 1984, and August, 1986. Malignant disease was found on 21 biopsies. Four were carcinoma in situ, and 17 were infiltrating carcinomas. Only three of the infiltrating carcinomas had metastasized to regional nodes, as confirmed by subsequent axillary dissection. Two of these metastatic tumors involved two nodes and the third only one. The findings on the remaining 79 biopsies were benign. Forty-eight mammograms were read as "benign"; all (100%) were benign pathologically. Thirty-one mammograms were considered "malignant"; 19 (61%) were malignant pathologically. Only two of the 21 mammograms given "suspicious" interpretations were malignant. Microcalcifications correlated with malignancy only 30% of the time (12/42).

Adult

Ovarian carcinoma metastatic to breast: a case report and review of the literature.

Breast metastasis from ovarian carcinoma is a rare event, with only 26 cases being previously reported in the English literature. The twenty-seventh such case is presented herein, and the literature on this topic is reviewed. Metastases to the breast from the ovary signal widespread metastases and generally herald a rapid deterioration and death. Although rare, it is important that metastatic cancer to the breast be differentiated from primary breast carcinoma as both the treatment and prognosis differ significantly.

Adult

Use of frozen section analysis in the treatment of basal cell carcinoma.

Frozen section margin verification has been used in the treatment of basal cell carcinoma at our institution for the past 13 years. A review of the last 450 cases has shown frozen section to be most helpful in treating recurrent tumors where microscopic tumor foci extend beyond clinical margins in 45% of cases. Frozen section analysis may be of value in selected patients with primary tumors, but its routine use is not indicated for the majority of these lesions, since complete excision is possible without relying on frozen section in 90% of cases.

Basal Cell Carcinoma

Responses of isolated pulmonary arteries to the C5a anaphylatoxin.

The anaphylatoxin C5a possesses spasmogenic activity in smooth muscle tissues. In this study, we examined the effect of C5a on isolated rabbit pulmonary artery (PA) ring segments under a variety of experimental conditions. C5a (1-100 nM) caused transient constriction of PA at resting tension. C5a-induced PA constriction was not affected by the histamine H1-receptor antagonist pyrilamine (1 microM) but was significantly decreased by the cyclooxygenase inhibitor indomethacin (1 microM). Disruption of the endothelial layer of the vessel had no effect on C5a activity in resting PA. PA, which had been preconstricted with norepinephrine (5 microM), exhibited a different response to C5a than PA at resting tension, however. C5a (1-10 nM) induced a biphasic response in preconstricted PA, initially causing further constriction followed by a greater degree of relaxation resulting in an overall decrease in PA tension. All responses of preconstricted PA to C5a were completely eliminated by indomethacin and significantly depressed by endothelial disruption. These data indicate that C5a interacts directly with isolated rabbit PA, but the nature of the PA response to this peptide depends on several variables including the presence or absence of active PA tension and cyclooxygenase metabolites, and the presence of intact endothelium.

Anaphylatoxins

Pentoxifylline relaxes isolated pulmonary arteries after preconstriction with norepinephrine.

Pentoxifylline (PTX) is a methylxanthine derivative which improves systemic microvascular flow and tissue oxygen delivery, presumably through actions on platelet aggregation and erythrocyte deformability. Although PTX also improves pulmonary vascular flow, recent evidence suggests that part of this improvement may be due to pulmonary vasodilation. To evaluate these effects we studied isolated rabbit lobar pulmonary artery (PA) ring segments to determine if PTX had direct effects on PA tissues and whether these effects could be modulated pharmacologically or by endothelial disruption. PTX had no effect on PA at resting tension. However, if the PA tension was actively increased by norepinephrine (5 microM), subsequent PTX application caused concentration-dependent PA relaxation. Relaxation occurred promptly and was maximal within 45-60 s. The threshold PTX concentration necessary for relaxation was 1 microM. PTX-induced relaxation was not affected by pretreatment with the cyclo-oxygenase inhibitor indomethacin (1 microM). Endothelial disruption by gentle rubbing of the intimal PA surface abolished relaxation of preconstricted PA by acetylcholine, but had no effect on relaxation by PTX. Although PA at resting tension displayed no response to PTX, PA constriction by norepinephrine in the presence of PTX concentrations greater than 10 microM was significantly decreased. These data indicate that PTX has direct actions on isolated rabbit PA which are not blocked by indomethacin nor require the presence of intact endothelium. Furthermore, PTX can suppress norepinephrine-induced constriction of isolated PA.

Animals

Venous access devices utilized in association with intensive cancer chemotherapy.

Consistent and reliable venous access is a major component of the management of patients with cancer undergoing chemotherapy. Venous access devices such as the long-term right atrial catheter and the subcutaneous port have become a major aspect of the supportive care of such individuals, with resultant advantages which have improved their quality of life. Yet, the occurrence of infectious and non-infectious complications restricts the usefulness of these devices and warrants a standardized approach to device placement, patient education and the management of such complications. Infectious complications, including exit site and tunnel infections, as well as bacteremias requiring catheter removal occur at a rate of approximately two episodes for every 1000 catheter days, while non-infectious complications occur more frequently. Uniform patient education and catheter care, as well as placement by a single consistent surgeon will decrease the frequency of complications, improve the longevity and function of these venous access devices, while minimizing the associated morbidity.

Antineoplastic Agents