A case of Creutzfeldt-Jakob disease (CJD) started with monoparesis of the left arm

PURPOSE: This study was undertaken to evaluate the potential metabolic complications of 1.5 percent glycine irrigating solution during endoscopic transanal resection (ETAR) of rectal tumors. METHODS: Thirteen consecutive frail patients (mean age, 81 (range, 57-91) years) undergoing 18 ETAR were prospectively studied from July 1993 to January 1995. Indications for ETAR included palliation of advanced rectal cancer (12 patients) and an extensive villous tumor (1 patient). A 27-French two-way Iglesias resectoscope was used. Packed cell volume, blood glucose, and serum concentrations of sodium, potassium, and creatinine were measured before, during (at 45 minutes), and after (at 6 and 24 hours) ETAR. Plasma concentration of glycine and hemoglobin levels were both measured preoperatively and at 45 minutes and 24 hours, respectively. Variables studied included resection time, volume and rate of irrigating fluid, height of irrigating fluid bag above operating table, resectate weight, occurrence of intraperitoneal and extraperitoneal perforation, blood loss, and clinical symptoms. RESULTS: Two patients were excluded. Mean operating time was 456 minutes. A mean of 192.3 liters of irrigant was infused into the rectum. Mean irrigation rate was 43,330 ml/minutes. Mean height of irrigating fluid bag was 692 cm. Extraperitoneal perforation occurred in two patients. Blood loss exceeded 200 ml in four patients, one of whom complained of nausea (operating time, 110 minutes). Mean rise in p-glycine at 45 minutes (10,028 mol/l; 387 percent of preoperative values) was significant (P = 0.006). Changes in packed cell volume, b-hemoglobin, b-glucose, s-sodium, and s-creatinine levels were not significant. There was significant correlation between p-glycine and s-creatinine levels at six hours (P = 0.033), between p-glycine levels and fall in s-sodium at 24 hours (P = 0.037), and between levels of b-hemoglobin and packed cell volume at 24 hours (P = 0.0004). There was a positive linear correlation between p-glycine and operating time (r = 0.7; P = 0.0026) and between p-glycine and volume of irrigating fluid (r = 0.5; P = 0.0386). CONCLUSIONS: Operating time best predicts increase of p-glycine in ETAR.     

Circumferential margin involvement after mesorectal excision of rectal cancer with curative intent. Predictor of survival but not local recurrence?

PURPOSE: This study examines the prognostic significance of circumferential margin involvement by tumor in resected specimens after potentially curative rectal cancer surgery. METHODS: During an eight-year period, all patients with rectal cancer were prospectively audited. For tumors of the middle and lower thirds of the rectum, a total mesorectal excision was performed; for tumor of the upper third, mesorectal excision proceeded at least 5 cm distal to the primary tumor. Resected specimens were subjected to careful histologic assessment, and patients undergoing curative procedures were entered into a surveillance program to detect both local and distant recurrence. RESULTS: Of 218 patients in the cohort, 9 had no resection, 14 underwent local excision, 1 had pre-operative radiotherapy, and 42 patients (20 percent) had palliative resections and were excluded from further analysis. This left 152 patients having a curative resection, of whom 20 (13 percent) had tumor within 1 mm of the circumferential margin. After follow-up until death or a median period of 41 months, recurrent disease was seen in 24 percent of patients with a negative margin and 50 percent with a positive margin. Both disease-free survival and mortality were significantly related to margin involvement (log-rank, P = 0.01 and P = 0.005, respectively). Local recurrence, however, was not significantly different in the two groups (11 and 15 percent, respectively; log-rank, P = 0.38). CONCLUSIONS: When mesorectal excision is performed, circumferential margin involvement is more an indicator of advance disease than inadequate local surgery. Patients with an involved margin may die from distant disease before local recurrence becomes apparent.     

Purification and characterization of a cytotoxin from Enterobacter cloacae

OBJECTIVE: To document our evolving surgical management of colonoscopic perforation and examine factors crucial to the improvement of patient care. DESIGN: We conducted a computer-based retrospective analysis of medical records (1980 through 1995). MATERIAL AND METHODS: Among 57,028 colonoscopic procedures performed, 43 patients (0.075%, or 1 perforation in 1,333 procedures) had a colonic perforation. Two additional patients were treated after colonoscopy performed elsewhere. The outcomes analyzed included surgical morbidity and mortality. RESULTS: Twenty-six women and 19 men who ranged in age from 28 to 85 years (median, 69) were treated for colonic perforation. More than 80% of perforations occurred during the latter half of the study period because of the increased volume of colonoscopic procedures (8 perforations among 12,581 examinations from 1980 through 1987 versus 35 perforations among 44,447 colonoscopies from 1988 through 1995). Emergency laparotomy was performed in 42 patients (93%). Perforations occurred throughout the colon: right side = 10; transverse = 9; and left side = 23. Three patients without evidence of peritoneal irritation fared well with nonoperative management. Most patients underwent primary repair or limited resection in conjunction with end-to-end anastomosis. In 14 patients (33%), an ostomy was created. One patient underwent laparotomy without further treatment. Intra-abdominal contamination ranged from none (31%) to local soiling (48%) to diffusely feculent (21%). Postoperative complications occurred in 12 patients and were associated with older age (P = 0.01), large perforations (P = 0.03), and prior hospitalization (P = 0.04). No postoperative deaths occurred. CONCLUSION: Despite a consistently low risk of colonic perforation, the increasing use of colonoscopy in our practice has resulted in an increased number of iatrogenic colonic perforations. In order to minimize morbidity and mortality, prompt operative intervention is the best strategy in most patients. Non-operative management is warranted in carefully selected patients without peritoneal irritation.     

Long-term follow-up of a prospective randomized study of endoscopic versus surgical treatment of bile duct calculi in patients with gallbladder in situ

Eighty-three patients with bile duct calculi were entered in a prospective randomized study of endoscopic sphincterotomy (ES) and stone removal (group 1) versus surgery alone (group 2), and were followed for more than 5 years. In group 1 endoscopic stone clearance was successful in 35 of 39 patients. Thirteen patients subsequently had cholecystectomy with (n = 7) or without (n = 6) biliary symptoms and one had a cholecystostomy for acute cholecystitis. Two patients have had mild biliary colic or pancreatitis. Two patients died from gallbladder carcinoma after 9 days and 18 months. In group 2 bile duct stones were cleared surgically in 37 of 41 patients. Late complications occurred in two patients (incisional hernia and recurrent stone). One patient with gallbladder carcinoma was cured and another died after 16 months. Early major and minor complications occurred in three and four respectively of 39 patients in group 1, and in three and six respectively of 41 patients in group 2. There were no deaths. During follow-up the total morbidity rate reached 28 percent (11 of 39) and 5 percent (two of 41) (P = 0.005) and the non-biliary related mortality rate was 31 percent (12 of 39) and 10 percent (four of 41) (P = 0.02) in groups 1 and 2 respectively. Nine patients in group 1 and two in group 2 died from heart disease (P = 0.02). Total hospital stay was 2-42 (median 13) days and 6-36 (median 16) days in groups 1 and 2 respectively (P not significant). Endoscopic and surgical treatment of bile duct calculi in middle-aged and elderly patients with gallbladder in situ are equally effective in the long term. However, the significantly increased mortality rate from heart disease in patients treated endoscopically compared with those treated surgically might speak in favour of operation.     

Writing in aphasia rehabilitation: cursive vs manuscript

An analysis of 100 patients sustaining multiple injury and pancreatic trauma was completed. Sixteen patients with penetrating injury died within the first 24 hours, 14 of whom died intraoperatively from major hepatic and/or retroperitoneal venous injury. Eighty-four patients survived long enough to permit evaluation of treatment. There was no statistically significant relationship between mode (p = 0.3) or anatomic area (p = 0.5) of injury and death. However, death was more common in the presence of duct injury (p less than 0.0001). Thirty-nine patients were determined to have duct injury and 45 did not. These two groups were equivalent, with the exception of a higher incidence of concomitant bowel injury (p less than 0.05) in those with duct violation. Combined sump and Penrose drainage was found to be adequate treatment of both proximal and distal nonductal injury with no significant difference in mortality or morbidity rates (p = 0.5). Resection of distal ductal injuries as opposed to drainage alone resulted in significantly lower morbidity and mortality rates (p less than 0.05), comparable to those of drained nonductal injuries. No conclusions could be made relevant to proximal duct injuries, except that drainage alone is inadequate. Seventeen (20 percent) of the 84 patients evaluated died. Pancreatic related mortality rate was 17 percent (14 patients). Two of 23 patients with blunt injury (9 percent) and 12 of 61 patients with penetrating injury (20 percent died). Gram-negative sepsis (82 percent) was the most common cause of death (p less than 0.01), and sepsis was correlated with the presence of pancreatic duct (p less than 0.0001) and bowel (p less than 0.001) injury.     

A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group

BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.     

Abdominal wound tumor recurrence after open and laparoscopic-assisted splenectomy in a murine model

PURPOSE: The cause of abdominal wall tumor recurrences after laparoscopic surgery for cancer remains unknown. A recent study from our laboratory using a murine splenic tumor model suggests that poor surgical technique (i.e., crushing of the tumor) and not the CO2 pneumoperitoneum is responsible for port wound tumors. However, in that experiment no actual laparoscopic procedure or manipulation was performed. The purpose of the current study was to determine the rate of abdominal wound tumors after laparoscopic-assisted splenectomy performed via a CO2 pneumoperitoneum vs. open splenectomy using the mouse splenic tumor model. METHODS: To establish splenic tumors, female BALB/c mice (N=72) were given subcapsular splenic injections of a 0.1-ml suspension containing 10(5) C-26 colon adenocarcinoma cells via a left flank incision at the initial procedure. Eight days later, animals were randomized into one of two groups: 1) laparoscopic-assisted splenectomy, or 2) open splenectomy. Laparoscopic-assisted splenectomy animals had three laparoscopic ports placed and then underwent laparoscopic mobilization of the spleen under a CO2 pneumoperitoneum followed by extracorporeal splenectomy via a subcostal incision. Group 2 animals underwent open splenectomy via a subcostal incision after three port incisions were made in the same locations as for laparoscopic-assisted splenectomy mice. The incision was closed after 20 minutes in both groups. Ten days later, the mice were killed and inspected for abdominal wall tumor implants. The experiment was performed via two separate trials. RESULTS: When results of the two trials were combined, there was no significant difference in the incidence of animals in each group with at least 1 port tumor (open, 21 percent; laparoscopic-assisted splenectomy, 33 percent; P=0.14). However, the overall incidence of port site tumors (number of ports with tumors/total number of ports for each group) was significantly higher in the laparoscopic-assisted splenectomy group than in the open group (20 vs. 7 percent; P=0.01). The subcostal incisional tumor recurrence rate was also higher in the laparoscopic-assisted splenectomy group (50 vs. 21 percent; P=0.02). as was the perioperative mortality rate (21 vs. 7 percent; P=0.08). Results of the two individual trials were also considered separately. The incidence of port wound tumors decreased significantly from the first to the second laparoscopic-assisted splenectomy trial (36 vs. 9 percent; P=0.003), although the incidence of tumors at the subcostal incision and the mortality rate for the two laparoscopic-assisted splenectomy group trials were not significantly different. The open group tumor incidences did not change from trial to trial. CONCLUSIONS: Overall, significantly more port and incisional tumors were noted in the laparoscopic-assisted group. Although not statistically significant, mortality rate of the laparoscopic-assisted group was higher than the open group. The reasons for these findings are unclear. Laparoscopic mobilization was quite difficult and required excessive splenic manipulation, which may have liberated tumor cells from the primary tumor and facilitated port tumor formation. With increased experience, less manipulation was required to complete mobilization. Of note, the incidence of port tumors in the laparoscopic-assisted splenectomy group decreased significantly from the first to the second trials; therefore, it is possible that surgical technique is a factor in port tumor formation. However, the persistently high tumor incidence at the subcostal incision site argues against the hypothesis that the second trial's laparoscopic mobilizations were less traumatic. The CO2 pneumoperitoneum may also be a factor. Further studies are warranted to clarify these issues.     

Fusaricidin A, a new depsipeptide antibiotic produced by Bacillus polymyxa KT-8. Taxonomy, fermentation, isolation, structure elucidation and biological activity

PURPOSE: This study was designed to examine variations in operative mortality among surgical specialists who perform colorectal surgery. METHODS: Mortality rates were compared between six board-certified colorectal surgeons and 33 other institutional surgeons using comparable colorectal procedure codes and a validated database indicating patient severity of illness. Thirty-five ICD-9-CM procedure codes were used to identify 2,805 patients who underwent colorectal surgery as their principal procedure between July 1986 and April 1994. Atlas, a state-legislated outcome database, was used by the hospital's Quality Assurance Department to rank the Admission Severity Group (ASG) of 1,753 patients from January 1989 to April 1994 (higher ASG, 0 to 4, indicates increasing medical instability). RESULTS: Colorectal surgeons had an eight-year mean in-hospital mortality rate of 1.4 percent compared with 7.3 percent by other institutional surgeons (P = 0.0001). There was a significantly lower mortality rate for colorectal surgeons compared with other institutional surgeons in ASG 2 (0.8 and 3.8 percent, respectively; P = 0.026) and ASG 3 (5.7 and 16.4 percent, respectively; P = 0.001). CONCLUSIONS: Board-certified colorectal surgeons had a lower in-hospital mortality rate than other institutional surgeons as patients' severity of illness increased.     

Rifabutin versus placebo in combination with three drugs in the treatment of nontuberculous mycobacterial infection in patients with AIDS

OBJECTIVE: Most endoscopic perforations of the colon occur in the rectosigmoid area and are thought to be secondary to direct injury from the endoscopic instrument. The aim of this study was to describe the mechanisms of injury and clinical outcome of endoscopic perforation involving the cecum. METHODS: Retrospective review of 6684 consecutive colonoscopic procedures performed at a university hospital over a 7-yr period. RESULTS: Colonoscopy was complicated by perforation in 0.22%. Five of the 15 perforations occurred in the cecum. The mean age of these five patients was 79.6 +/- 17.7 yr (mean +/- SD). Indications for the procedure were bleeding (n = 4) and suspected obstructing cecal mass (n = 1). Abnormal endoscopic findings included diverticulosis, vascular malformations, cecal ulcer/inflammation, mass, and polyps. Perforation was directly attributable to an ancillary procedure (three routine biopsies, one electrocautery) in the cecal area in four patients, and cecal pathology (inflammation, ulceration) was a contributing risk factor in three patients. Mortality was 80%. In contrast, a noncecal perforation usually occurred at the sigmoid region and was associated with technical difficulties, e.g., inability to traverse a stricture or reach the cecum. CONCLUSIONS: Routine forceps biopsy (without electrocautery) is an under-recognized cause of cecal perforation. Ancillary endoscopic interventions in the cecal region should be minimized in elderly patients with evidence of cecal inflammation. Pneumatic injury may be an additional risk factor for cecal perforation in patients with a colonic stricture or a tortuous colon.     

Improved outcome after emergency surgery for cancer of the large intestine

BACKGROUND: Emergency surgery for colorectal cancer has become more aggressive and radical over the past decade. This retrospective review analyses the impact on outcome. METHODS: The results of emergency surgery within 24 h of admission were compared between 1982 and 1987 (77 patients) and 1988 and 1993 (75 patients). Patient and tumour characteristics were similar in both groups. RESULTS: Right colonic obstruction or perforation was treated by primary resection and anastomosis in 11 of 12 patients before 1988 and in all 19 patients thereafter. Primary resection was also the treatment of choice for perforated cancer of the left colon and rectum before 18 of 20) and after (20 of 21) 1988. The rate of primary resection for obstructing cancer of the left colon and rectum increased from 17 of 45 to 30 of 35. One-stage resections for obstructing cancer were performed in ten of 45 and 22 of 35 patients before and after 1988 respectively. The overall mortality rate declined from 14 of 77 to three of 75 after 1988 (P< 0.01). The rate of radical lymphadenectomy rose from six of 46 patients to 42 of 69 after 1988. The 3-year survival rate increased from 50 to 74 per cent (P < 0.05). CONCLUSION: The data support further efforts towards improving the immediate and late outcome of emergency surgery in complicated colorectal cancer.     

Do "America's Best Hospitals" perform better for acute myocardial infarction?

BACKGROUND: "America's Best Hospitals," an influential list published annually by U.S. News and World Report, assesses the quality of hospitals. It is not known whether patients admitted to hospitals ranked at the top in cardiology have lower short-term mortality from acute myocardial infarction than those admitted to other hospitals or whether differences in mortality are explained by differential use of recommended therapies. METHODS: Using data from the Cooperative Cardiovascular Project on 149,177 elderly Medicare beneficiaries with acute myocardial infarction in 1994 or 1995, we examined the care and outcomes of patients admitted to three types of hospitals: those ranked high in cardiology (top-ranked hospitals); hospitals not in the top rank that had on-site facilities for cardiac catheterization, coronary angioplasty, and bypass surgery (similarly equipped hospitals); and the remaining hospitals (non-similarly equipped hospitals). We compared 30-day mortality; the rates of use of aspirin, beta-blockers, and reperfusion; and the relation of differences in rates of therapy to short-term mortality. RESULTS: Admission to a top-ranked hospital was associated with lower adjusted 30-day mortality (odds ratio, 0.87; 95 percent confidence interval, 0.76 to 1.00; P=0.05 for top-ranked hospitals vs. the others). Among patients without contraindications to therapy, top-ranked hospitals had significantly higher rates of use of aspirin (96.2 percent, as compared with 88.6 percent for similarly equipped hospitals and 83.4 percent for non-similarly equipped hospitals; P<0.01) and beta-blockers (75.0 percent vs. 61.8 percent and 58.7 percent, P<0.01), but lower rates of reperfusion therapy (61.0 percent vs. 70.7 percent and 65.6 percent, P=0.03). The survival advantage associated with admission to top-ranked hospitals was less strong after we adjusted for factors including the use of aspirin and beta-blockers (odds ratio, 0.94; 95 percent confidence interval, 0.82 to 1.08; P=0.38). CONCLUSIONS: Admission to a hospital ranked high on the list of "America's Best Hospitals" was associated with lower 30-day mortality among elderly patients with acute myocardial infarction. A substantial portion of the survival advantage may be associated with these hospitals' higher rates of use of aspirin and beta-blocker therapy.     

Neuropathology in the neurosciences. A system in transition

BACKGROUND: Despite the use of warfarin, major systemic embolism remains an important complication in patients with heart-valve replacement. Although the addition of antiplatelet agents has the potential to reduce this complication, their efficacy and safety when given in combination with warfarin are uncertain. METHODS: In a randomized, double-blind, placebo-controlled trial, we assessed the efficacy and safety of adding aspirin (100 mg per day) to warfarin treatment (target international normalized ratio, 3.0 to 4.5) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism. RESULTS: A total of 186 patients were randomly assigned to aspirin and 184 to placebo, and they were followed for up to 4 years (average, 2.5). Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients (1.9 percent per year) and 24 placebo-treated patients (8.5 percent per year) (risk reduction with aspirin, 77 percent; 95 percent confidence interval, 44 to 91 percent; P < 0.001). Major systemic embolism, nonfatal intracranial hemorrhage, or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin (3.9 percent per year) and 28 patients assigned to placebo (9.9 percent per year) (risk reduction, 61 per cent; 95 percent confidence interval, 24 to 80 percent; P = 0.005); major systemic embolism or death from any cause occurred in 13 patients (4.2 percent) and 33 patients (11.7 percent), respectively (risk reduction, 65 percent; 95 percent confidence interval, 33 to 82 percent; P < 0.001); and death from all causes occurred in 9 patients (2.8 percent) and 22 patients (7.4 percent), respectively (risk reduction, 63 percent; 95 percent confidence interval, 19 to 83 percent; P = 0.01). Bleeding occurred in 71 patients in the aspirin group (35.0 percent), as compared with 49 patients in the placebo group (22.0 percent) (increase in risk, 55 percent; 95 percent confidence interval, 8 to 124 percent; P = 0.02); major bleeding occurred in 24 and 19 patients, respectively (increase in risk, 27 percent; 95 percent confidence interval, -30 to 132 percent; P = 0.43). CONCLUSIONS: In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves, the addition of aspirin to warfarin therapy reduced mortality, particularly mortality from vascular causes, together with major systemic embolism. Although there was some increase in bleeding, the risk of the combined treatment was more than offset by the considerable benefit.     

Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma

PURPOSE: Traumatic sphincter disruption frequently is associated with a rectovaginal fistula, but the effect of a persistent sphincter defect on the outcome of rectovaginal fistula repair is poorly documented. We analyzed the outcome of rectovaginal fistula repairs based on preoperative sphincter status. PATIENTS AND METHODS: We identified 52 women who underwent 62 repairs of simple obstetrical rectovaginal fistulas between 1992 and 1995. Fourteen patients (27 percent) had preoperative endoanal ultrasound studies and 25 (48 percent) had anal manometry studies. Follow-up was by mailed questionnaire in 36 patients (69 percent) and by telephone interview in 12 (23 percent), for a total response rate of 92 percent. Median age was 30.5 (range, 18-70) years, and median follow-up was 15 (range, 0.5-123) months. Twenty-five patients (48 percent) complained of varying degrees of fecal incontinence before surgery. There were 27 endorectal advancement flaps and 35 sphincteroplasties (28 with and 8 without levatoroplasty). RESULTS: Success rates were 41 percent with endorectal advancement flaps and 80 percent with sphincteroplasties (96 percent success with and 33 percent without levatoroplasty; P = 0.0001). Endorectal advancement flap was successful in 50 percent of patients with normal sphincter function but in only 33 percent of patients with abnormal sphincter function (P = not significant). For sphincteroplasties, success rates were 73 vs. 84 percent for normal and abnormal sphincter function, respectively (P = not significant). Results were better after sphincteroplasties vs. endorectal advancement flaps in patients with sphincter defects identified by endoanal ultrasound (88 vs. 33 percent; P = not significant) and by manometry (86 vs. 33 percent; P = not significant). Poor results correlated with prior surgery in patients undergoing endorectal advancement flaps (45 percent vs. 25 percent; P = not significant) but not sphincteroplasties (80 vs. 75 percent; P = not significant). CONCLUSIONS: All patients with rectovaginal fistula should undergo preoperative evaluation for occult sphincter defects by endoanal ultrasound or anal manometry or both procedures. Local tissues are inadequate for endorectal advancement flap repairs in patients with sphincter defects and a history of previous repairs. Patients with clinical or anatomic sphincter defects should be treated by sphincteroplasty with levatoroplasty.     

Different prognostic effect of postoperative chemoradiation therapy on diploid and nondiploid high-risk rectal cancers

PURPOSE: DNA ploidy has been shown to play a role in the response to cytotoxic therapy in a variety of malignancies, including breast cancer and melanoma. However, the importance of DNA ploidy in rectal cancer is unknown. The aim of the present study was to determine whether ploidy status might be associated with response to postoperative chemoradiation in TNM Stages II to III rectal cancer. METHODS: This retrospective study analyzed data from 229 patients with TNM Stages II to III rectal cancer who underwent resection between 1979 and 1984. The ploidy status and treatment modalities in relation to outcome were assessed. RESULTS: The recurrence-free ten-year survival rate was 52.2 percent for patients with diploidy and 50.5 percent for patients with nondiploidy (P = 0.99). The ten-year survival rates for patients with diploidy and patients with nondiploidy were 55 and 19 percent (P = 0.016) in the chemoradiation group, and 51 and 60 percent (P = 0.15) in the nonchemoradiation group, respectively. In the chemoradiation group, DNA nondiploidy was associated with an increased recurrence rate (83.3 vs. 50.0 percent; P = 0.001). The interaction between DNA nondiploidy and chemoradiation remained important in predicting outcome in the Cox regression model. Factors independently correlated with a worse outcome included Stage IIIb (relative risk, 2.9; 95 percent confidence interval, 1.7-5; P = 0.0001), perineural invasion (relative risk, 2.5; 95 percent confidence interval, 1.6-4, P = 0.0001), distal tumor (relative risk, 1.7; 95 percent confidence interval, 1.1-2.7, P = 0.014), and nondiploidy with chemoradiation (relative risk, 2.9; 95 percent confidence interval, 1.2-7.2, P = 0.0213). CONCLUSIONS: These findings suggest that DNA nondiploidy is inversely correlated with long-term outcome among patients with high-risk rectal cancer receiving chemoradiation.     

Palliative treatment of malignant esophageal stenosis: experience with plastic versus metal stents

BACKGROUND/AIMS: We report on the palliative treatment of 44 patients with malignant dysphagia by placement of plastic (Celestin tubes, n = 24) vs metal stents (Wall stents, Nitinol stents, Gianturco stents, n = 20). METHODOLOGY: Prior to stent insertion, esophageal stenosis was dilated stepwise to 16 mm (plastic tube) and to 10 mm (metal stent). RESULTS: Stent insertion was technically successful in all cases and led to a reduction of dysphagia. Risk of perforation was comparable in both groups (n = 1 in each group). Most of the plastic stents were placed when the tumor was localized in the proximal part of the esophagus close to the upper esophageal sphincter, when esophageal-bronchial fistula was present and in the risk of fistula development after radiation. During follow-up, tumor ingrowth (TI) and stent migration (SM) were the major complications. Whereas tumor ingrowth predominantly occurred in metal stents (TI after 6 weeks, 45% vs. SM, 10%) that required repeated argon beamer therapy, tube migration and bolus impaction (BI) often occurred in patients with plastic stents (TI, 0% vs. SM, 16%; BI, 4%). CONCLUSIONS: The findings of the study suggest that the decision whether plastic tubes or metal stents used should be taken individually considering tumor localization, axis deviation and the presence of esophago-respiratory fistulas. When stepwise dilation of malignant stenoses is performed carefully, perforation risk appears not to be different between placement of plastic prostheses and metal stents.     

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.     

Effect of reperfusion on biventricular function and survival after right ventricular infarction

BACKGROUND: Although the salutary effects of reperfusion in patients with left ventricular infarction are well documented, the benefits in patients with acute right ventricular infarction are less clear. METHODS: To determine whether primary angioplasty improves right ventricular function and the clinical outcome in patients with right ventricular infarction, we performed echocardiographic studies before and after angioplasty in 53 patients with acute right ventricular infarction. RESULTS: Complete reperfusion, defined as normal flow in the right main coronary artery and its major right ventricular branches, was achieved in 41 patients (77 percent), leading to prompt and striking recovery of right ventricular function (mean [+/-SE] score for free-wall motion, 3.0+/-0.1 at base line and 1.4+/-0.1 at three days; P<0.001). Twelve patients (23 percent) had unsuccessful reperfusion, defined as the failure to restore right ventricular branch flow, with or without patency of the right main coronary artery. Unsuccessful reperfusion was associated with lack of recovery of right ventricular function (score for free-wall motion, 3.2+/-0.2 at base line and 3.0+/-0.9 at three days; P= 0.55), as well as persistent hypotension and low cardiac output (in 83 percent of the patients, vs. 12 percent of those with successful reperfusion; P=0.002) and a high mortality rate (58 percent, vs. 2 percent for those with successful reperfusion; P=0.001). CONCLUSIONS: In patients with right ventricular infarction, complete reperfusion of the right coronary artery by angioplasty results in the dramatic recovery of right ventricular performance and an excellent clinical outcome. In contrast, unsuccessful reperfusion is associated with impaired recovery of right ventricular function, persistent hemodynamic compromise, and a high mortality rate.     

Acetaminophen toxicity in an urban county hospital

BACKGROUND: The prevalence and characteristics of acetaminophen-associated liver injury in hospitalized patients are not well defined. METHODS: We identified patients hospitalized for excessive acetaminophen ingestion at an urban county hospital over a 40-month period (1992 to 1995) and reviewed their medical records to determine the incidence and clinical features of the ingestions and their outcomes. RESULTS: Of the 71 patients studied, 50 were classified as having taken acetaminophen during suicide attempts and 21 as having accidentally poisoned themselves while attempting to relieve pain. The suicidal patients had ingested almost twice as much acetaminophen as those in the accidental-overdose group (median, 20 vs. 12 g; P=0.009). Among the patients for whom data were available, 63 percent of those in the accidental-overdose group and 25 percent of those in the suicidal group had chronic alcohol abuse (P=0.009). The patients in the accidental-overdose group more often had severe liver necrosis (aminotransferase levels, >3500 IU per liter; 52 percent vs. 14 percent; P=0.002), and were more likely to have hepatic coma (33 percent vs. 6 percent, P=0.006). There were four deaths (19 percent) in the accidental-overdose group and one (2 percent) in the suicidal group (P=0.04). Five patients -- three in the accidental-overdose group and two in the suicidal group -- had ingested 4 g of acetaminophen or less. Acetaminophen ingestion accounted for 12 percent of all patients hospitalized with overdoses (71 of 589) and 40 percent of patients with acute liver failure (10 of 25) during the study period. CONCLUSIONS: In an urban county hospital, patients hospitalized with acetaminophen toxicity related to accidental misuse had higher rates of morbidity and mortality than those who attempted suicide, even though the latter had taken more acetaminophen. A higher frequency of chronic alcohol abuse among the patients with accidental overdoses may be one explanation.     

A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. Myocardial Infarction Triage and Intervention Investigators

BACKGROUND: Several relatively small randomized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infarction. These results, however, have not been duplicated other than in investigational trials. METHODS: We compared mortality during hospitalization and long-term mortality, as well as the use of resources, among 1050 patients in a primary-angioplasty group and 2095 patients in a thrombolytic-therapy group. Patients were selected from the Myocardial Infarction Triage and Intervention Project Registry cohort of 12,331 consecutive patients admitted with acute myocardial infarction to 19 Seattle hospitals between 1988 and 1994. Because of the potential for selection bias, several subgroup analyses were performed that included patients eligible for thrombolysis, high-risk patients, and patients in the primary-angioplasty group who were treated at hospitals with high volumes of angioplasty. RESULTS: There was no significant difference in mortality during hospitalization or long-term follow-up between patients in the thrombolytic-therapy group and those in the primary-angioplasty group (mortality during hospitalization, 5.6 percent and 5.5 percent, respectively; P=0.93; adjusted hazard ratio for the risk of death within three years after primary angioplasty, 0.95; 95 percent confidence interval, 0.8 to 1.2). There was also no significant difference in mortality between high-risk subgroups of patients in the two treatment groups. The rates of procedures and costs were lower among patients in the thrombolytic-therapy group both at the time of hospital discharge and after three years of follow-up (30 percent fewer coronary angiograms, 15 percent fewer coronary angioplasties, and 13 percent lower costs after three years of follow-up). CONCLUSIONS: In a community setting, we observed no benefit in terms of either mortality or the use of resources with a strategy of primary angioplasty rather than thrombolytic therapy in a large cohort of patients with acute myocardial infarction.     

Expression of carbohydrate antigen sialyl Le(a): a new functional prognostic factor in gastric cancer

PURPOSE: The prognostic value of the altered expression of carbohydrate antigens sialyl Le(a) (sLe(a)) and sialyl Le(x) (sLe(x)), which have been implicated as functional ligands in heterotypic-cell-adhesion systems in the multistep process of tumor metastasis, were evaluated. PATIENTS AND METHODS: The level of expression of sLe(a) and sLe(x) antigens was examined immunohistochemically in paraffin-embedded tumor samples from 137 patients who underwent resection for gastric cancer. Correlation between the antigens' expression, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. RESULTS: Tumors that were positive for the sLe(a) antigen were significantly more likely to be large (P = .035), to be localized at the proximal third of the stomach (P = .018), to have an infiltrate appearance (P = .013), to have an invasive mode both in depth of invasion (P = .028) and in lymphatic invasion (P = .002), and to be classified as late stage (P = .011) than those that were negative for sLe(a), whereas the sLe(x) antigen status was not correlated with any clinicopathologic factors. The overall survival of patients with an sLe(a)-antigen-positive tumor was significantly poorer than that of those with an sLe(a)-antigen-negative tumor (P = .0001). Survival within each pathologic stage differed also (stage I, P = .030; stage II, P = .046; stage III, P = .026, respectively). A Cox regression analysis with multiple covariates showed that positive sLe(a) antigen status was an independent prognostic factor for a worse outcome in patients with gastric cancer. According to the mode of recurrence, increased sLe(a) antigen expression significantly affected both peritoneal dissemination and liver metastasis. CONCLUSION: Increased expression of the sLe(a) antigen may serve as a potent prognostic indicator for recurrence in patients with gastric cancer. Careful follow-up and intensive therapy are required for patients with an sLe(a)-antigen-positive gastric cancer.