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Biomedical subjects

R V Lord

Publications and source records attributed to R V Lord.

At least 37 records · Page 2Linked to original sources
PubMed2000

Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia.

OBJECTIVE: To compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers. SUMMARY BACKGROUND DATA: The p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level. METHODS: DNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n = 19), cardia (esophagogastric junction, n = 12), or subcardia (n = 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with single-strand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor. RESULTS: p53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar. CONCLUSIONS: Adenocarcinomas of the esophagus and cardia have a similar frequency and spectrum of p53 gene mutations, suggesting that these tumors have a common pathogenesis. Patients with mutations are younger, have signs of more advanced disease, and have a poorer prognosis than patients without mutations.

Adenocarcinoma↗
PubMed2000

Optimal treatment for localized esophageal cancer still uncertain.

These articles both report the results of multi-institutional, randomized, phase 3 trials for the treatment of patients with localized (T1-3 N0-1 M0) esophageal squamous cell carcinoma (SCC) or esophageal adenocarcinoma. Both studies were initiated and coordinated by the Radiation Therapy Oncology Group (RTOG) but included patients enrolled by other study groups as well. Cooper et al. report late follow-up results for the RTOG 85-01 trial that was conducted between 1986 and 1990. This trial randomized patients to either radiation therapy (RT) alone (RT, 64 Gy in 32 fractions over 6.4 wk, n = 62) or combined RT and chemotherapy (50 Gy in 25 fractions over 5 wk, plus cisplatin 75 mg/m2 i.v. on first day of wk 1, 5, 8, and 11, and continuous infusion fluorouracil (5FU) 1 g/m2 per day on the first 4 days of the same weeks, n = 61). Most (82%) of the patients had SCC. Eight percent of the cohort randomly assigned to combined modality therapy experienced acute life-threatening toxic effects, and an additional 2% died as a direct consequence of treatment. The randomized trial was halted in 1990 when an interim analysis found a highly significant difference in survival favoring the combined therapy group, after which 73 consecutive patients were enrolled into a nonrandomized study offering only the combined therapy regimen. At 5-yr of follow-up, the overall survival rate for the combined therapy group in the randomized study was 26% (95% CI, 15-37%) compared with 0% for RT alone. In the nonrandomized study, the 5-yr overall survival rate was 14% (95% CI, 6-23%). The histopathological type of tumor did not significantly influence survival. Cooper et al. now report that 22% of the randomized combined modality group survived at least 8 yr after treatment, and that there were no deaths caused by esophageal cancer after 5 yr post-treatment. The study reported by Kelsen et al. included 440 patients with esophageal adenocarcinoma (n = 236) or SCC (n = 204) randomized to either preoperative chemotherapy plus esophagectomy or to esophagectomy alone. The chemotherapy regimen consisted of three cycles of preoperative cisplatin and 5FU and two cycles after operation for responding patients. Doses were higher than those used in the RTOG 85-01 trial. Although radiation therapy was not part of the treatment plan, it could be given in some circumstances. There was no significant difference in median survival (14.9 months for chemotherapy plus surgery compared with 16.1 months for surgery alone), and there were also no significant differences in 1-yr, 2-yr, 3-yr, or disease-free survival rates. There were no significant differences in survival between patients with adenocarcinoma and those with SCC. A clinical response to chemotherapy, as assessed by barium contrast radiography, was found in 19% of patients who received chemotherapy. A complete pathological response was found in 2.5% of patients. There was no significant increase in operative complications in the chemotherapy treated group.

Adenocarcinoma↗
PubMed1999

Endoscopic grading of the gastroesophageal valve in patients with symptoms of gastroesophageal reflux disease (GERD).

BACKGROUND: It has been suggested that endoscopic grading of the gastroesophageal flap valve is a good predictor of the reflux status. METHODS: To test this hypothesis, 268 symptomatic patients underwent endoscopic grading of the gastroesophageal valve using Hill's classification, with grades I through IV. Esophageal acid exposure, lower esophageal sphincter characteristics, and the degree of esophageal mucosal injury were compared among the groups. RESULTS: The prevalence of a mechanically defective sphincter, abnormal esophageal acid exposure, erosive esophagitis, and Barrett's esophagus increased with increasing alteration of the gastroesophageal valve. The presence of a grade IV valve indicated increased esophageal acid exposure in 75% of patients. As a predictor, this is similar to lower esophageal sphincter pressure but not as good as the presence of esophageal mucosal injury. CONCLUSIONS: Endoscopic grading of the gastroesophageal valve provides useful information about the reflux status but is less useful as an indicator of gastroesophageal reflux disease (GERD) than the presence of esophageal mucosal injury.

Adolescent↗
PubMed1998

Cholecystectomy in cardiothoracic organ transplant recipients.

OBJECTIVES: To assess the risks associated with cholelithiasis and cholecystectomy in cardiothoracic organ transplant recipients at this hospital and to identify any differences with potential causal significance between the group with known gallstones and the transplant recipient group as a whole. DESIGN: Medical records survey. SETTING: Tertiary care university hospital. PATIENTS: Six hundred forty-five patients had cardiothoracic organ transplantation at this hospital between February 1, 1984, and May 31, 1996. Gallstones were detected in 37 (5.7%) of these patients and 32 patients underwent cholecystectomy, of which 29 operations were performed primarily for symptomatic gallstone disease. All cholecystectomies were performed after transplantation. MAIN OUTCOME MEASURES: Mortality, morbidity, postoperative biliary disease. RESULTS: Patients with gallstones were significantly older than the transplant patient group as a whole (Student t test, P=.001); they were more likely to be female (chi2 test, P=.05); and they had a higher body mass index (t test, P=.001). There were no significant differences in the maximum serum bilirubin level during the transplantation admission, incidence of diabetes mellitus, cholestyramine use, or cyclosporine dosage during the first 12 months after transplantation. Cholecystectomy was performed after a median 5-month symptomatic period, mostly by the minilaparotomy method. Forty-five percent of cholecystectomies were urgent or semi-urgent. One patient died of lung infection on the second postoperative day. The median postoperative stay was 3 days. At a median 33 months' follow-up, 4 patients have had further biliary problems (2 patients with common bile duct stones, 1 patient with intrahepatic stones, and 1 patient with biliary dyskinesia). Four other patients with asymptomatic gallstones who did not receive cholecystectomy have remained asymptomatic for between 15 and 67 months. CONCLUSIONS: Cholecystectomy by the minilaparotomy or laparoscopic methods, with routine operative cholangiography, is the preferred treatment for symptomatic gallstones in cardiothoracic organ transplant recipients. Although the optimum management of asymptomatic gallstones in these patients remains unclear, our favorable experience with a policy of reserving cholecystectomy for symptomatic cases seems noteworthy.

Adolescent↗
PubMed1998

Splenectomy for HIV-related immune thrombocytopenia: comparison with results of splenectomy for non-HIV immune thrombocytopenic purpura.

OBJECTIVE: To determine the effectiveness and safety of splenectomy for patients with human immunodeficiency virus (HIV)-related immune thrombocytopenia, using the results of splenectomy for patients with non-HIV immune thrombocytopenic purpura as a control group for comparison. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PATIENTS: Fourteen patients who underwent splenectomy for symptomatic, medically refractory HIV-related immune thrombocytopenia at this hospital from 1988 to 1997. During the same period, 20 patients had splenectomy for treatment of non-HIV immune thrombocytopenic purpura. INTERVENTION: Splenectomy. MAIN OUTCOME MEASURES: Platelet response, need for postsplenectomy medical therapy, progression of HIV disease, and complications. RESULTS: All patients with HIV-related thrombocytopenia had a complete early platelet response to splenectomy, with an elevation of the platelet count to greater than 100X10(9)/L. After a median follow-up of 26.5 months, all but 1 patient had a sustained complete remission with no need for medical therapy for thrombocytopenia. Splenectomy was more effective in the HIV-related thrombocytopenia group than in the non-HIV immune thrombocytopenic purpura group, with significantly higher platelet counts at 1 week and 1 month after splenectomy in the HIV group (t test, P=.02 and P=.009, respectively). There were significantly fewer patients needing medical therapy for thrombocytopenia after splenectomy in the HIV group (chi2 test, P=.02). There were no remarkable short- or long-term complications in the patients with HIV infection, including no overwhelming postsplenectomy infections. Three patients have died, and 2 patients have developed AIDS since operation. CONCLUSIONS: Splenectomy is effective treatment for patients with symptomatic HIV-related thrombocytopenia that is resistant to medical therapy. The effectiveness of this treatment suggests that the predominant mechanism of thrombocytopenia in HIV-infected patients is increased destruction of platelets because of platelet-associated immunoproteins.

Adolescent↗
PubMed1998

Incidence of deep vein thrombosis after laparoscopic vs minilaparotomy cholecystectomy.

OBJECTIVES: To determine the frequency of deep vein thrombosis (DVT) associated with minimally invasive cholecystectomy and to determine, using minilaparotomy cholecystectomy as a control operation, the influence of the laparoscopic pneumoperitoneum on DVT formation. DESIGN: Prospective nonrandomized control trial. SETTING: Tertiary care university hospital. PATIENTS: One hundred consecutive patients intended to undergo either laparoscopic cholecystectomy (59 patients) or minilaparotomy cholecystectomy (41 patients) with either of 2 surgeons were prospectively enrolled between April 1996 and April 1997. The minilaparotomy cholecystectomy group served as controls to isolate the effect of the pneumoperitoneum. Patient details, operative details, and any thromboembolic or bleeding complications were recorded. The same thromboprophylaxis regimen was prescribed for each group; namely, preoperative and postoperative subcutaneous low-molecular-weight heparin (LMWH), graduated compression stockings, and intraoperative intermittent calf compression. INTERVENTION: Minimally invasive cholecystectomy. MAIN OUTCOME MEASURE: Frequency of DVT. Bilateral lower limb venous color duplex scanning was used to detect DVT. Scans were performed on 3 occasions: (1) preoperatively on admission to hospital, (2) on the first postoperative day, and (3) between 2 and 4 weeks postoperatively. RESULTS: Three patients in the laparoscopic group and 2 patients in the minilaparotomy group underwent conversion to conventional open cholecystectomy. There were no significant differences between patients in the 2 groups for age, sex, body mass index, preoperative white blood cell count, platelet count, prothrombin time, or activated partial thromboplastin time. There were no significant differences between the 2 groups for elective vs emergency operations, public hospital vs private hospital admissions, or consultant vs resident surgeon. Macroscopic gallbladder pathology grades for both groups were not significantly different, and there was no significant difference in the duration of postoperative hospital stay. Operative cholangiography was performed in a significantly larger proportion of laparoscopic cases (86% vs 66% in the minilaparotomy group; chi(2) test, P=.002), and the duration of anesthesia was significantly longer for the laparoscopic operation (118 minutes vs 98 minutes; t test, P=.05). Ninety-seven patients received preoperative LMWH and all patients received graduated compression stockings, intraoperative intermittent calf compression, and postoperative LMWH. Two of the 100 patients had postoperative DVT, 1 after laparoscopic cholecystectomy and 1 after minilaparotomy cholecystectomy. Both DVTs were detected by duplex examination on the first postoperative day. The DVT found after laparoscopic cholecystectomy was in 1 of the 3 patients who did not receive preoperative LMWH. There were no DVTs in any of the 40 patients who had an additional duplex scan between 2 and 4 weeks after operation. CONCLUSIONS: Despite the theoretical risk of thromboembolic disease due to use of the laparoscopic pneumoperitoneum, the frequency of DVT after either laparoscopic cholecystectomy or minilaparotomy cholecystectomy is low if adequate thromboprophylaxis is provided.

Cholecystectomy, Laparoscopic↗
PubMed1998

Rising incidence of oesophageal adenocarcinoma in men in Australia.

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982-1993 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance (P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall.

Adenocarcinoma↗
PubMed1997

Anorectal surgery in patients infected with human immunodeficiency virus: factors associated with delayed wound healing.

OBJECTIVE: A review of all anorectal operations in patients infected with human immunodeficiency virus (HIV) was performed to assess the incidence, variety, and clinical course of anorectal disease in these patients and to identify factors influencing wound healing. SUMMARY BACKGROUND DATA: Anorectal disease is the most common indication for surgical intervention in patients infected with HIV. The cause and management of HIV-related anorectal conditions, which differ significantly from non-HIV-related diseases, are not clear. There also is considerable variation in the reported results of surgical procedures, including wound healing. St. Vincent's Hospital, Sydney, is situated in an area with the highest concentration of individuals infected with HIV in Australia. METHODS: The medical records of all identified patients infected with HIV who had an anorectal operation at St. Vincent's General Hospital between January 1, 1988, and January 31, 1995, were reviewed retrospectively. Logistic regression, Mann-Whitney U test, and Fisher's exact tests were used for analysis. RESULTS: One thousand five hundred two patients with acquired immune deficiency syndrome (AIDS), equivalent to 26.8% of all known patients with AIDS in Australia at this time, were admitted to this hospital during the 7-year period. One hundred one patients infected with HIV underwent 161 anorectal operations. All patients were male homosexuals (98 patients, 97%) or bisexuals (3 patients, 3%), with intravenous drug use an additional risk factor in 5 patients (5%). Thirty-seven percent of patients had more than one operation. Seventy-two percent of patients were Centers for Disease Control (CDC) group 4 (AIDS) at operation, 27% were group 2, 1% was group 3, and none were group 1. Accurate information about wound healing was available for 74% of first operations, and univariate and multivariate logistic analyses of these showed that when the CD4+ T-lymphocyte count was <50 cells/ microL, healing was significantly retarded (p = 0.016). The Centers for Disease Control group, patient age, and serum albumin were not significant predictors of wound healing. The interval between HIV diagnosis and operation was not associated with impaired wound healing, but recognition of AIDS more than 1 year before operation was associated with significantly better wound healing compared with those in whom AIDS developed within the year before operation (p = 0.025). In the patients for whom accurate wound healing information was available, only 40% had healed their wounds by 3 months after operation. Wound healing was worst for patients with chronic fissures, only 16% of whom had healed their wounds at 3 months. The wound healing rate was worse for repeat operations than for first operations. Ten percent of patients had anorectal malignancies, none of which were diagnosed clinically before or during operation. CONCLUSIONS: Wound healing is a significant problem after anorectal operations in patients infected with HIV, especially when the CD4 count is <50/microL. Although there seems to be little or no benefit from more invasive operations in some cases, thorough examination with adequate biopsies is required in all cases. The best management of anorectal disease in patients infected with HIV still is unclear.

Adult↗
PubMed1997

Gastric cancer in the bypassed segment after operation for morbid obesity.

A case is reported in which two separate adenocarcinomas were detected in the bypassed distal stomach 13 years after gastric stapling with loop gastro-enterostomy was performed for the treatment of morbid obesity. Retrograde endoscopy via the afferent loop was used to establish the diagnosis. Although gastritis and metaplasia have been described in the bypassed stomach, only one case of carcinoma in this area has previously been reported.

Adenocarcinoma↗