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Biomedical subjects

S R Evans

Publications and source records attributed to S R Evans.

At least 55 records · Page 3Linked to original sources

The effect of extracellular calcium on colonocytes: evidence for differential responsiveness based upon degree of cell differentiation.

Calcium supplementation decreases the incidence of colon cancer in animal models and may prevent colon cancer in man. Potential mechanisms include binding of mitogens and direct effects of calcium on colonic epithelial cells. In this study, the effects of extracellular calcium on epithelial cell growth and differentiation were studied in three colon carcinoma and two colonic adenoma cell lines. The characteristics studied included morphology, cell cycle kinetics, [Ca2+]IC (intracellular calcium concentration), proliferation, and expression of differentiation markers such as carcinoembryonic antigen (CEA) and alkaline phosphatase (AP). Sodium butyrate (NaB) and 1,25-dihydroxyvitamin D3 were used as controls in the latter three assays as these two agents are known differentiating agents. Alteration of [Ca+2]EC (extracellular calcium concentration) did not affect carcinoembryonic antigen (CEA) or alkaline phosphatase (AP) expression. NaB enhanced the expression of AP three-fold and CEA five-fold. This effect was augmented by increasing [Ca2+]EC. The exposure of cells to 1,25-(OH)2-Vitamin D3 increased CEA but not AP. [Ca2+]IC increased in response to 1,25-(OH)2-vitamin D3 and NaB but not with variation in [Ca2+]EC. Increased [Ca2+]EC inhibited proliferation of well-differentiated cells, but had no effect on poorly-differentiated cells. Morphological studies showed that extracellular calcium was necessary for normal cell-cell interactions. These studies have demonstrated direct effects of calcium on colonic epithelial cells which may contribute to the protective effects of dietary calcium against colon cancer. Loss of responsiveness to the antiproliferative effects of [Ca2+]EC with de-differentiation suggests that calcium supplementation may be most beneficial prior to the development of neoplastic changes in colonic epithelium.

Alkaline Phosphatase↗

Radical treatment of locally recurrent gastric cancer.

Locally recurrent gastric cancer develops in 45 per cent of resected patients. This study assessed the impact of an aggressive search for recurrence after radical operations and the use of reoperative and adjuvant therapy in this setting. From 1983 to 1990, 75 patients were explored for regionally recurrent gastric cancer. Resection was possible in 40 (53.5%), and palliative bypass was possible in 19 (25.3%); exploration only was performed in 16 (21.4%). Among resectable patients, gastrectomy was performed in 22 (55%) and gastrectomy with adjacent organ resection in 18 (45%) with an overall operative mortality of 15% (6 patients). Mean duration of life after bypass was 3.1 months; after exploration 4.5 months. Fifteen (40.6%) were not candidates for radiation or chemotherapy, 13 (31.2%) received preoperative radiotherapy (20 Gy), and 12 (28.2%) received postoperative systemic chemotherapy. Two-year survival after radical treatment was as follows: surgery alone 20%; radiotherapy and surgery 31.3%; surgery and chemotherapy 66.4%. These preliminary results indicate that re-excision benefits selected patients with recurrent gastric cancer. Patients receiving radiotherapy and chemotherapy tended toward improved survival.

Adult↗

Growth inhibition of HT-29 human colon cancer cells by analogues of 1,25-dihydroxyvitamin D3.

The use of 1,25-dihydroxyvitamin D3 as an antiproliferative agent in the treatment of cancer is limited by its hypercalcemic effects. Analogues with equivalent or greater antiproliferative activities but smaller hypercalcemic effects have been developed. The antiproliferative effects of 1,25-dihydroxyvitamin D3 and four analogues were studied in HT-29 and SW620 human colon cancer cell lines, moderate and low expressors of the vitamin D receptor, respectively. HT-29 is a primary, moderately differentiated, cell line, while SW620 is metastatic and poorly differentiated. Growth curve studies, proliferation assays, and clonogenic assays were used to assess the antiproliferative effects of 1,25-dihydroxyvitamin D3, 1,25-dihydroxy-16-ene-23-yne-D3, 1,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne-D3, 1,25-dihydroxy-16,23E-diene-26,27-hexafluoro-D3, and 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3. Growth of HT-29 cells was significantly inhibited by all four analogues at 10(-8) M (P < 0.05). Analogues 1,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne-D3, 1,25-dihydroxy-16,23E-diene-26,27-hexafluoro-D3, and 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3 were 2 times as potent as analogue 1,25-dihydroxy-16-ene-23-yne-D3 and 1,25-dihydroxyvitamin D3. SW620 cells did not show any growth inhibition with any of the compounds tested. The affinities of the three most potent analogues for the vitamin D receptor were similar to that of 1,25-dihydroxyvitamin D3, while that of analogue 1,25-dihydroxy-16-ene-23-yne-D3 was lower. These results demonstrate that, as in leukemic cells, analogues of 1,25-dihydroxyvitamin D3 are potent antiproliferative agents in colon cancer cells and this activity is most likely mediated through the vitamin D receptor.

Alkaline Phosphatase↗

Vitamin D receptors in breast cancer cells.

1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.

Adenocarcinoma↗

Effect of mitomycin C, verapamil, and hyperthermia on human gastric adenocarcinoma.

The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of mitomycin C (MMC), used at different concentrations, in inhibiting the growth of human gastric adenocarcinoma (AGS) cells. Combined verapamil and hyperthermia treatment resulted in a significant decrease in cell count by 72.2% as compared with the control value. Verapamil drastically enhanced the growth-inhibitory activity of MMC at high concentration against AGS cells by 67.5% and had no effect at intermediate and low concentrations. Hyperthermia did not enhance the effect of MMC on AGS cells. The modalities analyzed in this study require further investigation and may have potential for in vivo studies on gastric cancer therapy in the near future.

Adenocarcinoma↗

Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma.

In order to devitalize maximally tumour tissue and improve the prognosis of gastric cancer patients, a method employing preoperative intensive radiotherapy with local hyperthermia as adjuvant treatment was evaluated. In order to estimate the effectiveness of preoperative intensive radiation and radiation with local microwave hyperthermia in radical gastric cancer treatment, 293 patients were randomized into three respective treatment groups: surgery alone, surgery preceded by preoperative radiation; and surgery followed by preoperative radiation and hyperthermia. Preoperative radiation therapy to a total dose of 20 Gy in four 5 Gy fractions did not improve 3- or 5-year survival in gastric cancer patients in comparison with surgery alone. Local hyperthermia in combination with radiation therapy followed by surgery produced a significant improvement in 3-year survival of 22.1% (from 35.5 +/- 4.9% to 57.6 +/- 6.3%, P < 0.05) and 5-year survival of 21.3% (from 30.1 +/- 4.7 to 51.4 +/- 6.6%, P < 0.05). In unresectable gastric cancer patients, radiation therapy and radiation therapy with hyperthermia both increase mean survival. In conclusion; intensive preoperative radiation therapy in total dose 20 Gy plus local microwave hyperthermia significantly improved 3- and 5-year survival in comparison with surgery alone. Further development and evaluation of equipment to produce reliable and safe delivery systems for hyperthermia is needed.

Adult↗

Antitumour activity of 5-fluorouracil, verapamil and hyperthermia against human gastric adenocarcinoma cell (AGS) in vitro.

The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of 5-fluorouracil (5-FU), used at different concentrations, in inhibiting the growth of gastric adenocarcinoma cells. Combined verapamil and hyperthermia treatment showed a significant decrease in cell count when compared to control (72.2%), hyperthermia alone (68.4%), or verapamil alone (65%). At a high concentration of 5-FU (50 micrograms/ml), verapamil and hyperthermia had an additive growth inhibitory effect over a 4-day period when compared to control. A combination of 5-FU at low concentration (0.5 microgram/ml) with verapamil significantly suppressed growth by 31.2% in comparison to control--with this effect being independent of the duration of treatment. The modalities analysed in this study require further investigation and have potential for clinical applicability to gastric cancer therapy in the future.

Adenocarcinoma↗

Ectopic breast cancer: case report and literature review.

Ectopic breast tissue includes both supernumerary and aberrant breast tissue. The incidence of supernumerary tissue has been reported as high as 6% depending on the ethnic group studied. The incidence of aberrant breast tissue remains unknown. The development of malignancy within these anomalies is rare. In the following paper, the case report of a patient with an ectopic breast cancer and a second primary cancer of the left anatomic breast is described. A review of the world literature on ectopic breast cancer follows. Specific characteristics of ectopic breast cancer are defined and recommendations for management are made.

Breast↗

Primary lymphoma of the appendix. Case report and review of the literature.

Malignant lymphomas comprise 1-4% of the malignant neoplasms of the gastrointestinal tract, but appendiceal lymphomas are exceedingly rare. Herein is presented a case of a well differentiated lymphocytic lymphoma of the appendix found incidentally at hernia repair. Forty-six cases of appendiceal lymphoma have been reported since 1898 with a mean patient age of 25.7 years. Thirty-one patients presented with right lower quadrant pain, and a mass was an incidental finding in five. Of the 46 cases, follow-up was possible in 28. There were four deaths within 30 days of the operation and five deaths within 1 year. Although extensive follow-up is limited, there have been only two reported deaths secondary to primary appendiceal lymphoma since 1945 and these two cases are discussed in detail. Based on this extensive review, appropriate recommendations are made.

Aged↗

The clinical impact of risk factor analysis and prophylaxis on pulmonary embolism.

Pulmonary emboli cause 50,000 deaths annually despite recognized risk factors and methods of prophylaxis. To determine the impact of risk factor analysis and the use of prophylaxis, a retrospective chart review of patients suffering pulmonary embolism (PE) at Georgetown University Hospital was performed. During a fifty-month period, 25,000 surgical and 36,000 nonsurgical admissions included 171 cases of PE. The incidence of PE among surgical patients was 0.24% (n = 61) and was 0.30% (n = 110) among nonsurgical patients as confirmed in 82% by pulmonary angiography or high-probability ventilation/perfusion scans. PE prophylaxis included pneumatic stockings, low-dose heparin, combination low-dose heparin/stockings, and coumarin. However, prophylactic measures were absent in 23% of the surgical and in all the nonsurgical patients suffering PE. On the basis of established criteria (SVS/ISCVS), 57% of surgical patients suffering PE were considered at high risk as compared with 13% of nonsurgical patients. Conversely, 54% of nonsurgical patients suffering a PE were considered to be at low risk. Standard treatment modalities were instituted after nonfatal PE: anticoagulation (61%), inferior vena cava filter (14%), and anticoagulation/filter (6%). While risk factor analysis identifies high-risk surgical patients, it may be less effective in identifying nonsurgical patients at increased risk for PE.

Adult↗

Three-dimensional models of the abdominal vasculature based on helical CT: usefulness in patients with pancreatic neoplasms.

Three-dimensional (3D) rendering of helical (spiral) CT data is used increasingly to show abnormalities of the vascular system [1]. Abdominal applications have focused mainly on the arterial system, but the portal venous system also can be depicted effectively with this technique. In patients with pancreaticobiliary neoplasms, axial display of helical CT images generally allows accurate staging of the lesion [2, 3]. Many surgeons, however, continue to request arteriography to specifically look for evidence of vascular encasement that would preclude surgery or vascular anomalies that would alter the surgical approach [4, 5]. The purpose of this essay is to illustrate the value of 3D rendering of CT data in providing useful information for surgical planning and showing the extent of vascular involvement by tumor.

Abdomen↗

1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition.

The antiproliferative action of 1,25-dihydroxyvitamin D3 in osteosarcoma, breast carcinoma, and colon carcinoma cell lines has been described. In this study, the level of vitamin D receptor was analyzed in a panel of colon adenoma and adenocarcinoma cell lines and the receptor level was correlated with the response to treatment with 1,25-dihydroxyvitamin D3. Ribonuclease protection and ligand-binding assays quantitated the level of vitamin D receptor mRNA expression and the level of functional receptors, respectively. The more well-differentiated cell lines, such as VACO 330, showed higher levels of vitamin D receptor than less-differentiated cell lines, such as SW620. Proliferation assay, clonogenic assay, and growth curve study in HT29 and SW620 cell lines assessed the antiproliferative effect of 1,25-dihydroxyvitamin D3 at concentrations ranging from 10(-11) to 10(-6) M. HT29 showed significant (P < 0.05) growth inhibition at 10(-9) to 10(-6) M concentrations, but growth of SW620 remained unchanged. The amount of vitamin D receptor in 12 malignant colonic tumors was compared with that of adjacent normal tissue, and in 9 cases, the tumor expressed a lower vitamin D receptor level. Our results suggest that the level of vitamin D receptor correlates with the degree of differentiation in human colon cancer cell lines and may serve as a useful biological marker in predicting clinical outcome in patients.

Adenoma↗

Laparoscopic cholecystectomy. Postoperative sonographic findings.

Seventeen consecutive patients undergoing elective laparoscopic cholecystectomy (LC) were serially evaluated with transabdominal ultrasound before, one day after, and six days after LC to document what, if any, changes occur in the surgical bed and surrounding parenchyma. The most common postoperative finding was focal sonolucency in the hepatic parenchyma adjacent to the gallbladder fossa in six (35%) of 17 patients. Five patients (29%) had postoperative fluid collections in the gallbladder fossa; in four of these five, it was technically difficult to dissect the gallbladder from the liver at the time of original surgery. In one patient the fluid resolved by the sixth postoperative day. It persisted in the remaining four. Two patients had transient ductal dilation and one had pneumobilia. Shadowing and ring-down artifact was identified in 12 patients due to surgical clips in the triangle of Calot. Because gallbladder fossa fluid may persist up to six days after uncomplicated laparoscopic cholecystectomy, caution should be used before attaching significance to isolated imaging findings. Clinical judgement remains the best means of selecting which patients need additional evaluation.

Abdomen↗

Obstructive uropathy secondary to massive inguinoscrotal bladder herniation.

The bladder is partially involved in 1 to 4% of all inguinal hernias. However, few cases of massive inguinoscrotal herniation of the bladder have been described, all of which have involved unilateral hydronephrosis. We report on a 45-year-old man with incomplete voiding and massively enlarged right scrotum along with elevated creatinine who was found to have massive inguinoscrotal herniation. Preoperative computerized tomography showed bilateral hydronephrosis. Herniorrhaphy was successfully done through an inguinal incision. The left kidney regained normal function with a decrease in creatinine levels. This case is atypical because of the presence of massive inguinoscrotal herniation with bilateral hydronephrosis. Computerized tomography has proved to be a valuable tool in diagnosing such cases. Surgical repair and reduction of hernia can be accomplished through an inguinal incision.

Genital Diseases, Male↗

Laparoscopic cholecystectomy: intraoperative ultrasound of the extrahepatic biliary tree and the natural history of postoperative transabdominal ultrasound findings.

Laparoscopic cholecystectomy (LC) has been rapidly embraced as an alternative to conventional open cholecystectomy (OC). While LC is less invasive than OC, it is still a surgical procedure with potential complications such as retained bile duct stones, iatrogenic injury to the bile duct with or without bile leak, hemorrhage, intestinal injury, and abscess formation. This article discusses the feasibility of intraoperative transmural ultrasound of the extrahepatic biliary tree with a 6.2 French catheter-based ultrasound probe and reviews the natural history of postoperative changes in the liver and gallbladder bed with conventional transabdominal ultrasound.

Abdomen↗

Acute appendicitis and the use of intraperitoneal cultures.

We reviewed the charts of 200 patients with a preoperative diagnosis of acute appendicitis (AA) to evaluate the influence and use of intraoperative culture results on patient management and antibiotic selection. Cultures were obtained in 66 percent of patients; 16 percent of the cultures in patients with AA yielded positive results versus 88 percent of cultures in patients with perforated or gangrenous appendicitis (complicated appendicitis [CA]) and in nine patients, positive cultures were used to adjust antibiotic therapy. Patients with CA who had antibiotic changes based on culture results had a complication rate of 25 percent versus a 29 percent rate for this group as a whole. We conclude that intraoperative cultures in patients with AA are rarely positive and do not influence antibiotic therapy or patient management. In CA, antibiotic changes based on culture results do not seem to alter patient outcome. Surgeons tend to rely on the proved efficacy of empiric antibiotic therapy and other basic surgical principles to afford the best outcome for their patients. The routine practice of obtaining peritoneal cultures in patients operated upon for AA and CA should be abandoned.

Acute Disease↗

Identifying the low-risk patient with penetrating colonic injury for selective use of primary repair.

As the mortality rate for penetrating colonic injuries approaches zero, emphasis has shifted toward reducing associated morbidity. This study was done to identify patients at low risk for colon-related extensive morbidity after primary repair of a penetrating colonic injury. The records of 100 consecutive patients admitted to the District of Columbia General Hospital (DCGH) between 1984 to 1990, surviving more than 24 hours after full-thickness penetrating colonic injuries, were retrospectively reviewed. Data collection included mechanism, management and anatomic location of the colonic injury. Severity of injury was evaluated by the Trauma Score (TS), Penetrating Abdominal Trauma Index (PATI), Flint Colon Injury Score (FCIS), time in the operating room, blood transfused during the first 24 hours and presence of preoperative shock (systolic blood pressure less than 90 millimeters of mercury). Mechanism of injury included 97 gunshot wounds and three stab wounds. Fifty-seven patients had primary repair (17 having resection and anastomosis) and 43 had colostomy. The anatomic location of injury was right colon in 37, transverse colon in 27, left colon in 35 and multiple sites (two) in one patient. In this series, only two patients had colon-related extensive morbidity--a parastomal hernia and wound dehiscence, both requiring operative intervention. There were no instances of intraperitoneal abscess formation. One patient died from overwhelming pneumonia after segmental resection of the colon with primary anastomosis. The literature reports a 12 to 42 percent colon-related morbidity rate in patients sustaining penetrating colonic injuries. This series from DCGH represents the lowest colon-related extensive morbidity and mortality rates reported to date in any substantial series of penetrating abdominal trauma. We attribute the 2 percent extensive morbidity rate to high TS (mean of 15.7), low PATI (mean of 24.2), low FCIS (mean of 1.9) and few associated intra-abdominal injuries (59 percent of patients with less than two). We have identified a group of patients with full-thickness penetrating injuries to the colon, few associated intra-abdominal injuries, high TS, low PATI and low FCIS who can be managed safely and judiciously by primary repair without undue morbidity and mortality.

Colon↗