Ruth S. Hassanein

Patterns of failure after curative resection of pancreatic carcinoma

Thirty‐six patients underwent curative resection of a primary pancreatic carcinoma from January 1977 to September 1987; 26 had Whipple resections, seven had total pancreatectomies, and three had distal pancreatectomies. Twenty‐six patients manifested recurrent disease, four died of intercurrent disease, and six were apparently cured. Median survival was 11.5 months with actuarial survival at 2 and 5 years of 32% and 17%, respectively. of the eventual recurrences, 19% were local only (pancreatic bed, regional nodes, adjacent organs, and immediately adjacent peritoneum) and 73% had a component of local failure. All patients failing did so with a component in the intraabdominal cavity. Peritoneal (42%) and hepatic failures (62%) were common. Extraabdominal metastases were documented in only 27%, but never as a sole site. Fourteen patient and tumor characteristics were evaluated for any relationships with failure or survival. No single variable independently predicted for local failure. However, a group of three (age > 60 years, T2 or T3 stage, and location of tumor in the body or tail) was associated with a substantial local failure risk (85% of all patients with local failure). Multivariate analysis showed that low tumor grade (P = 0.002), female sex (P = 0.002), and adjuvant radiation (P = 0.02) were all independent predictors of prolonged survival. Ten patients were treated in an adjacent setting. Those given 55 Gy or greater had improved local control (50% versus 25%) and cure (33% versus none) when compared with patients treated to lower doses. The authors conclude that local failure after curative resection remains a significant problem and further efforts to improve local control are warranted. However, peritoneal and hepatic relapses occur frequently. Thus, adjuvant treatment strategies using wide‐field radiation techniques or intraperitoneal therapy, in combination with local tumor bed irradiation and chemotherapy, should be explored.

Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma

OBJECTIVE:Our goal was a prospective follow-up of Barretts esophagus to determine what clinical, endoscopic, and histological features at the time of initial diagnosis are predictive of the development of Barretts adenocarcinoma or multifocal high-grade dysplasia (HGD).METHODS:Newly diagnosed Barretts esophagus patients were prospectively followed with a standardized endoscopic and bioptic surveillance protocol. Features examined by χ2 and stepwise logistic regression analyses as potential predictors the development of multifocal HGD or adenocarcinoma included age, length of Barretts segment, hiatal hernia size, severity of dysplasia at diagnosis, severity of dysplasia during surveillance, and type of long-term medical treatment.RESULTS:One hundred-eight Barretts patients have had follow-up ranging from 12 months to 101 months (mean ± SD, 39.9 ± 20.8 months), for a total of 361.8 patient-years. Overall, five patients developed multifocal HGD and five developed adenocarcinoma. The incidence of adenocarcinoma as well as multifocal HGD was 1 per 71.9 patient-years. χ2 analysis showed progression to Barretts multifocal HGD/adenocarcinoma was associated with hiatal hernia (p= 0.02), the length of Barretts (p= 0.001), the presence of dysplasia at diagnoses (p < 0.001) or anytime during surveillance (p < 0.001). Stepwise logistic regression analysis revealed progression to multifocal HGD or adenocarcinoma was significantly and independently associated with presence of dysplasia at diagnosis (p < 0.0001) or anytime during follow-up (p < 0.03), hiatal hernia size (p < 0.02, for hernia ≥3 cm), and length of Barretts (p= 0.009, >2 cm).CONCLUSIONS:Endoscopic and histological features of Barretts esophagus patients at initial diagnosis are predictive of risk of progression to cancer.

Amitriptyline in the prophylaxis of migraine: Effectiveness and relationship of antimigraine and antidepressant effects

Amitriptyline was evaluated as a prophylactic antimigraine agent in 110 patients with severe migraine. This agent improved the migraine more than 50 percent in 72 percent of patients and more than 80 percent in 57 percent of patients. Most of the 31 patients with less than 50 percent improvement had virtually no response. Depression, measured with the Zung Self-Rating Depression Scale, was absent in 40 patients, borderline in 53, and moderate to severe in 17. Overall, depression ratings improved minimally with therapy. There was a weak relationship between improvement in depression and improvement in migraine. Subgroups with a stronger correlation of these could not be found. This work suggests that amitriptyline is effective in migraine prophylaxis and that it has a primary effect on migraine that is relatively independent of its antidepressant action.

Vertigo, Motion Sickness and Migraine

SYNOPSIS

Platelet aggregability in migraine.

Employing optical density methods, platelet aggregation in response to 1.275, 1.7, and 3.4 μM adenosine diphosphate was tested in 46 patients with migraine and 46 controls matched by age, sex, and race. The migraine patients demonstrated platelet hyperaggregability when compared with controls, as manifested by a lower threshold forthe platelet-release reaction and increased platelet stickiness following aggregation. There was no correlation of platelet hyperaggregability with the severity of migraine or with the occurrence of migraine-associated neurologic symptoms, suggesting that platelet hyperaggregability is a concomitant feature of the migraine syndrome but not dependent on the occurrence of the actual headache. As platelet hyperaggregability may predispose to development of intravascular platelet aggregates or mural thrombi, the hyperaggregability found here may help explain the increased incidence of stroke and heart attack in migraine patients that has been reported elsewhere.

Risk Stratification of Barrett's Esophagus: Updated Prospective Multivariate Analysis

OBJECTIVES:Prospective evaluation of Barretts esophagus (BE) in order to determine what demographic, endoscopic, and histologic features are predictive of the prevalence and incidence of Barretts high-grade dysplasia (HGD) and adenocarcinoma (Ca).METHODS:Newly diagnosed BE patients were entered into and followed in a standardized surveillance protocol. The following features were examined using either forward, stepwise multiple regression analysis, or Cox proportional hazards to determine their ability to predict the presence of HGD or Ca at index BE diagnosis as well as their ability to predict progression of BE during follow-up: age, race, gender, length of BE in cm, size of a hiatal hernia, severity of dysplasia at index diagnosis as well as during surveillance, gastric Helicobacter pylori infection status, and type of medical acid-reflux treatment.RESULTS:A total of 550 patients were diagnosed with BE over the study period. Stepwise multiple regression analysis showed three factors significantly associated with index diagnosis of HGD or Ca: hiatal hernia (larger size), Barretts length (longer length), and absence of H. pylori infection. Three hundred and twenty-four BE entered the surveillance protocol. Cox proportional hazards models revealed a significant and independent association for five factors predictive of the time to progression of BE: presence of dysplasia at index diagnosis (p < 0.001), severity of dysplasia during surveillance (p < 0.001), length of Barretts epithelium (p = 0.012), size of hiatal hernia (p = 0.006), and gastric H. pylori infection status (p = 0.023).CONCLUSIONS:Endoscopic and histologic features of BE at initial diagnosis are predictive of index HGD and cancer as well as with risk of BE progression.

Prognosis in Patients with Transient Ischemic Attacks

The prognosis on 144 patients with transient ischemic attacks was determined over a minimum period of three years by quantitating, at intervals, the number of attacks and also the neurological disability by means of a disability score. No patients had neurological disability at the initiation of the study. Total cervicocephalic angiography was performed on 93 patients. Seven of the 144 patients were deceased at the end of the three-year period, five of them due to strokes. Seventeen patients (15.6%) developed persistent neurological disability during the three years, with the mean disability score being much higher for the patients with carotid attacks than those with basilar attacks. The cumulative number of attacks in both carotid and basilar groups rose steadily in the first 18 months, with a much larger number of attacks occurring in the basilar group. The attack rate leveled off after 18 months in the carotid group. Attacks tended to be consistent in nature over a period of time. Twenty-eight percent of those patients with basilar attacks and 12.5% of those patients with carotid attacks showed carotid stenosis on angiography. Study of carotid stenosis associated with subsequent neurological disability revealed that increased risk occurred only when carotid stenosis was more than 70%

Platelet aggregation, stroke, and transient ischemic attack in middle‐aged and elderly patients

Platelet aggregation was studied with optical density methods in a group of 39 patients with stroke or transient ischemic attacks (TIA) and in age, sex, and race-matched controls. The patients were divided at age 60 into young stroke patients and young controls (18 pairs) and old stroke patients and old controls (21 pairs). A semiquantitative measure of the threshold of phase II of platelet aggregation and extent of disaggregation 3 minutes after peak aggregation were used as an index of platelet aggregability. Aggregability was significantly greater in young stroke patients than in young controls. Aggregability was similar in old stroke patients and old controls. Both old stroke patients and old controls were hyperaggregable compared with young controls, indicating that aggregability rises with age. This suggests that platelet aggregability is a significant risk factor for stroke but is relatively more important in the younger than in the older stroke patient.

Migraine in Twins Raised Together and Apart

History of headache and migraine diagnosed by structured interview utilizing International Headache Society criteria was obtained in two samples of female twin pairs—154 raised together and 43 raised apart since infancy. Zygosity was determined by standard methods. Probandwise concordance rates were determined. Assuming that liability to migraine has a multifactorial etiology involving a number of genetic and environmental risk factors acting additively, tetrachoric correlations in the four groups of twins (monozygotic raised together, monozygotic raised apart, dizygotic raised together, and dizygotic raised apart) were then calculated. The genetic and environmental influences in the liability to migraine were estimated using biometrical model‐fitting methods.

Anal cancer in women.

We studied predisposing factors in 56 women with anal cancer, comparing them with 56 matched controls drawn from the population. A detailed pretested questionnaire was administered to each study subject in a structured interview and blood was drawn for detection of herpes simplex virus antibodies by radioimmunoassay. Pathologic material from cases was obtained and evidence of human papilloma virus infection was sought. By univariate analyses we found associations between anal cancer and positive herpes simplex virus 2 titer (p = 0.0017), cigarette smoking (p = 0.0028), previous positive or questionable cervical Papanicolaou smear (p = 0.0124), and increasing number of sexual partners (p = 0.0224). By the multivariate technique of logistic regression there were independent and significant associations with cigarette smoking (p = 0.0126), previous use of hemorrhoid preparations (p = 0.0149), and history of disturbed bowel habits for greater than 1 mo (p = 0.0273). Anal cancer in women is a rare disease associated with cigarette smoking and sexual experience. Its association with previous anorectal disease is unclear and deserving of further study.