William Silen

Edema of the arm as a function of the extent of axillary surgery in patients with stage I–II carcinoma of the breast treated with primary radiotherapy

Edema of the arm can be a significant complication following treatment of breast cancer. To determine the risk of arm edema and factors associated with this risk in patients treated with primary radiotherapy, we reviewed the records of 475 women with early breast cancer treated between 1968 and 1980. During this period, the use of axillary surgery prior to radiation gradually increased, and all patients received full axillary irradiation until late in the series. Based on the surgeons report, the extent of axillary surgery was classified as either a sampling, a lower dissection, or a full dissection. Edema of the arm was scored on clinical grounds and ranged from mild hand swelling to an increased arm circumference of 8 cm. At 6 years, the actuarial risk of developing arm edema was 8% for the entire study population. This risk was 13% for 240 patients who had axillary surgery and 4% for 235 patients not undergoing axillary surgery (p = 0.006). For patients undergoing axillary surgery, the risk of arm edema was 37% with full dissection compared to 5% with sampling (p = 0.0003), and 8% with lower dissection (p = 0.03). The risk of arm edema at 6 years was 28% if more than ten nodes were removed, and 9% if one to ten nodes were removed (p = 0.03). However, the extent of axillary dissection was stronger predictor of subsequent edema than was the number of nodes obtained. The role of axillary irradiation could not be evaluated since 91% of patients received axillary irradiation. The use of chemotherapy, the site or size of the primary tumor, clinical nodal status, patient age and weight, type of suture, the use of a drain, and subsequent local or distant failure did not appear to be significant risk factors. We conclude that the combination of full dissection and full axillary irradiation results in an unacceptably high risk of arm edema.

Antacid titration in the prevention of acute gastrointestinal bleeding: a controlled, randomized trial in 100 critically ill patients.

We randomized 100 critically ill patients at risk of developing acute gastrointestinal ulceration and bleeding into two groups. One (51 patients) received antacid prophylaxis, and the other (49 patients) received no specific form of prophylaxis. Hourly antacid titration kept the pH of the gastric contents above 3.5. Two of the 51 patients who received antacid prophylaxis and gastrointestinal bleeding. Twelve of the 49 control patients bled (P less than 0.005). Of the 12 patients in the control group who bled, seven were placed on antacid medication, and all seven apparently stopped bleeding. Analysis of all the patients showed that an increasing prevalence of respiratory, failure, sepsis, peritonitis, jaundice, renal failure and hypotension was correlated with a greater frequency of bleeding. No patients required operative treatment to control bleeding. These data indicate that the occurrence of acute gastrointestinal bleeding in critically ill patients can be reduced by antacid titration.

Antacid versus cimetidine in preventing acute gastrointestinal bleeding. A randomized trial in 75 critically ill patients.

Over a 15-month period, 75 critically ill patients at risk of acute gastrointestinal bleeding were randomized into two groups: one group (38 patients) received the H2-blocker cimetidine intravenously at an initial dosage of 300 mg every six hours, and the other group (37 patients) received antacid (Mylanta II) through a nasogastric tube at an intial dosage of 30 ml every hour. Gastric pH was measured hourly and titrated above 3.5. Upper-gastrointestinal-tract bleeding occurred in seven of 38 cimetidine-treated patients but in none of 37 antacid-treated patients (P less than 0.01). When antacid titration was added to the cimetidine regimen in four of seven patients with bleeding, all four stopped bleeding. Renal failure, sepsis, peritonitis, hypotension, respiratory failure, jaundice, multiple trauma, and major operative procedures were associated with an increased incidence of bleeding. Cimetidine does not adequately protect seriously ill patients from acute upper-gastrointestinal-tract bleeding. Antacid is better for this purpose.

Respiratory Failure, Hypotension, Sepsis, and Jaundice A Clinical Syndrome Associated with Lethal Hemorrhage from Acute Stress Ulceration of the Stomach

Abstract A clinical syndrome of massive bleeding from acute multiple gastric ulcers associated with respiratory failure, hypotension, sepsis, and jaundice developed in eight of 150 consecutive patients admitted to the respiratory-surgical intensive care unit of the Beth Israel Hospital. These ulcers were almost exclusively located in the fundus of the stomach. Only one of these eight patients survived. Twenty-one gastric secretory studies performed in eighteen critically ill patients indicate that increased secretion of acid may be an important cause of this disease. One patient in whom acute gastric ulceration later developed had a maximally stimulated parietal cell mass in the basal state. Patients in whom this lethal complication develops and who do not respond to nonoperative therapy are probably best treated by gastric resection and vagotomy.

Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer

The time-course of local failure following conservative surgery and radiotherapy (S+RT) for early breast cancer is not well established. We therefore examined the time-course and patterns of breast recurrence as a first site of treatment failure in a group of 607 AJCC clinical Stage I or II invasive breast carcinomas treated from 1968-81. Sixty-seven patients had a breast failure (11%), corresponding to 5- and 10-year actuarial rates of 10% and 16%. The hazard rate (i.e., the risk per unit time of a failure) for any breast failure increased over the first 2 years, was fairly constant at about 2.5%/year over the period from 2 to 6 years after treatment, and then decreased to about 1%/year at 8 years. The majority of failures were at or near the primary tumor site (33 true recurrences (TR) and 15 marginal misses (MM). In addition there were 12 failures at sites at least several cm from the boosted volume (E), 6 recurrences in the skin without a parenchymal mass (S), and 1 patient with an unclassifiable failure. Recurrences at or near the primary site (TR/MM) occurred earlier (median 38.5 mo, range 12-87 mo) than recurrences at distant sites in the breast (E) (median 64.5 mo, range 26-90). The hazard rate for TR/MM increased over the first 2-1/2 years to reach approximately 2%/year, remained at that level till about 5 years after treatment, and then decreased to about 0.5%/year at 8 years following RT. By contrast, the hazard rate for E increased slowly with time to approximately 1%/year at 5 years, with little change in the rate after that time. We conclude that the time-course of the development of local recurrence after S+RT is protracted. The majority of failures appear at or near the primary tumor site; these are seen mainly in the first 7 years following RT. Recurrences at distant sites in the breast have an even more protracted time-course. Such recurrences are rare in the first 4 years following RT. Our results emphasize the need to obtain long follow-up in these patients, both to detect these recurrences promptly and to properly evaluate the results of S+RT.

Fibrocystic Disease of the Breast — A Nondisease?

Is fibrocystic disease really a distinct entity? Is it a diagnosis that can be made clinically or histologically? Does this designation imply an increased risk of breast cancer? Should we attempt t...

The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.

Studies of the pH Gradient and Thickness of Frog Gastric Mucus Gel

The role of mucus in protecting the underlying gastric epithelium is unknown. We investigated the pH gradient and thickness of the mucus gel layer in in vitro gastric fundic mucosa mounted in a special chamber using an antimony microelectrode, a slit lamp, and a dissecting microscope (× 40). This system allowed visualization of the tip of the electrode as it entered the mucus gel and as it reached the mucosa. With luminal pH maintained at 3.0-3.5, the maximum pH at interface between mucus and cells was 6.50 ± 0.10 (n = 9). At luminal pH 3.0-3.5, an increase in nutrient [HCO3-] from 17.8 to 47.8 δM resulted in an increase in maximum pH within the mucus from 6.80 ± 0.20 to 7.60 ± 0.20 (p

Effects of morphine analgesia on diagnostic accuracy in emergency department patients with abdominal pain: a prospective, randomized trial ☆

BACKGROUND Because of concerns about masking important physical findings, there is controversy surrounding whether it is safe to provide analgesia to patients with undifferentiated abdominal pain. The purpose of this study was to address the effects of analgesia on the physical examination and diagnostic accuracy for patients with abdominal pain. STUDY DESIGN The study was a prospective, double-blind clinical trial in which adult Emergency Department (ED) patients with undifferentiated abdominal pain were randomized to receive placebo (control group, n = 36) or morphine sulphate (MS group, n = 38). Diagnostic and physical examination assessments were recorded before and after a 60-minute period during which study medication was titrated. Diagnostic accuracy and physical examination changes were compared between groups using univariate statistical analyses. RESULTS There were no differences between control and MS groups with respect to changes in physical or diagnostic accuracy. The overall likelihood of change in severity of tenderness was similar in MS (37.7%) as compared with control (35.3%) patients (risk ratio [RR] 1.07, 95% confidence interval [CI] 0.64-1.78). MS patients were no more likely than controls to have a change in pain location (34.0% versus 41.2%, RR 0.82, 95% CI 0.50-1.36). Diagnostic accuracy did not differ between MS and control groups (64.2% versus 66.7%, RR 0.96, 95% CI 0.73-1.27). There were no differences between groups with respect to likelihood of any change occurring in the diagnostic list (37.7% versus 31.4%, RR 1.20, 95% CI 0.71-2.05). Correlation with clinical course and final diagnosis revealed no instance of masking of physical examination findings. CONCLUSIONS Results of this study support a practice of early provision of analgesia to patients with undifferentiated abdominal pain.

Ultrastructural Evidence for Piecemeal and Anaphylactic Degranulation of Human Gut Mucosal Mast Cells in vivo

One hundred and seventeen coded intestinal biopsies were examined by electron microscopy and evaluated for morphological evidence of mast cell and basophil secretion in situ. Sixty percent of the biopsies had evidence of secretion. Mast cell secretion was evident in control biopsies, many of which were obtained from uninvolved tissues of patients with inflammatory bowel disease. Biopsies of inflamed continent pouches from ulcerative colitis (UC) patients showed more mast cell secretion than noninflamed UC pouch biopsies. This evidence of mast cell secretion supports recent work that documents high constitutive levels of histamine in jejunal fluids of Crohns disease patients and suggests a proinflammatory role for mast cells in inflammation associated with pouchitis.