LaSalle D. Leffall

Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis

Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.

Alarming increase of the cancer mortality in the u.s. black population (1950–1967)

The U.S. cancer mortality per 100,000 for both sexes rose, from 1950 to 1967, for blacks from 147 to 177, an increase of 20%, while it remained unchanged for whites at 150. The female cancer mortality rate declined for blacks from 146 to 142, a decrease of only 3%, while it declined for whites from 139 to 126, a decrease of 9%. The male cancer mortality rate rose for blacks from 147 to 220, an increase of 50%, while it increased for whites from 158 to 181, an increase of only 16%. In 1950, the cancer mortality rate for both sexes was 2% lower for blacks than for whites, but, by 1967, it had become 18% higher. Of the 58 most frequent U.S. sex‐specified cancer types, 29 increased slower in whites, 9 decreased faster in whites, 14 showed no significant differences, and only 4 (malignant melanoma and reticulum cell sarcoma in both sexes) increased faster in whites. Environmental factors are the most likely causes for this alarming rise of cancer in U.S. blacks.

Estrogen and progesterone receptors in breast cancer in black americans. Correlation of receptor data with tumor differentiation

It has been observed that 60–70% of breast cancer patients have estrogen receptors (ER) and that nearly two‐thirds of such patients respond favorably to endocrine therapy. Cytosolic ER and progesterone receptors (PgR) have been evaluated in the current study, among 146 black women with breast cancer in order to determine whether the distribution of ER and PgR differs from the national norm. The results showed following trends that were similar to reports from other institutions: (1) postmenopausal patients and primary tumors showed higher ER positivity than premenopausal patients and metastatic sites, respectively; (2) a significant correlation between the ER positivity and tumor grade; and (3) a higher PgR positivity in ER‐positive patients than in ER‐negative patients. However, statistically significant differences were observed in three parameters when compared to reports from other institutions on white patients: (1) a low incidence of ER‐positive (46%) and high incidence of ER‐negative (42%) tumors; (2) a higher incidence of poorly differentiated (55.5%) and a lower incidence of well differentiated (5.5%) tumors; tumor grade was independent of age, menopausal status, histopathology and stage; and (3) a higher percentage of patients discovered at a more advanced stage of the disease. The clinical implications of these results in explaining the relatively poorer survival of black women with breast cancer compared to whites is discussed. Whether this high incidence of PD tumors and thus a high incidence of ER negativity is due to ethnic differences and/or environmental and other factors remains to be elucidated.

Molecular Breast Cancer Subtypes in Premenopausal African-American Women, Tumor Biologic Factors and Clinical Outcome

IntroductionBreast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women.MethodsA retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998–2005, was performed.ResultsThe luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01).The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31).ConclusionThe high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.

Clinical aids in strangulation intestinal obstruction

Summary The following findings and their frequency were noted in seventy-four patients with strangulation intestinal obstruction: (1) abdominal tenderness, 82 per cent; (2) tachycardia, 70 per cent; (3) leukocytosis, 64 per cent; (4) severe, constant, and frequent back pain, 58 per cent; (5) fever, 52 per cent; (6) shock guarding, 31 per cent; (7) palpable abdominal mass or irreducible hernia, 29 per cent; (8) shock (hypotension), 28 per cent; (9) subnormal temperature, 19 per cent; and (10) bloody diarrhea, 5 per cent. Peritoneal tap aided in some doubtful cases but x-ray findings were not consistently helpful. Fourteen patients were admitted with other primary diagnoses—pancreatitis, appendicitis, salpingitis, and twisted ovarian cyst—who later proved to have strangulation intestinal obstruction. Apparently, the single most important factor delaying correct diagnosis in these cases was the failure to recognize the common occurrence of signs of peritonitis in patients with strangulation intestinal obstruction. Careful search for signs and symptoms of strangulation intestinal obstruction should lead to earlier diagnosis and treatment with subsequently lower mortality.

Early-stage gallbladder cancer in the Surveillance, Epidemiology, and End Results database: effect of extended surgical resection.

HYPOTHESIS Extended surgical resection (ESR) may improve survival in patients with early-stage primary gallbladder cancer. DESIGN Retrospective analysis of findings in the Surveillance, Epidemiology, and End Results (SEER) database. SETTING Academic research. PATIENTS Individuals with potentially surgically curable gallbladder cancer (Tis, T1, or T2) who underwent a surgical procedure. MAIN OUTCOME MEASURES Overall survival, number of lymph nodes (LNs) excised, and results of simple cholecystectomy vs ESR. RESULTS We identified 3209 patients with early-stage gallbladder cancer (11.7% Tis, 30.1% T1, and 58.2% T2). On multivariate analysis, decreased survival was noted among patients older than 60 years (hazard ratio, 1.57; 95% confidence interval, 1.30-1.90), among patients with more advanced cancer (1.99; 1.46-2.70 for T1; 3.29; 2.45-4.43 for T2), and among patients with disease-positive LNs (1.65; 1.39-1.95 for regional; 2.58; 1.54-4.34 for distant) (P < .001 for all), while increased survival was observed among female patients (0.82; 0.70-0.96; P = .02) and among patients undergoing ESR (0.59; 0.45-0.78; P < .001). The survival advantage of ESR was seen only in patients with T2 lesions (0.49; 0.35-0.68; P < .001). Lymph node excision data were available for a subset of 2507 patients, of whom 68.2% had no LN excised, 28.2% had 1 to 4 LNs excised, and 3.6% had 5 or more LNs excised. On multivariate analysis, patients with 1 to 4 LNs excised had a survival benefit over those with no LN excised (HR, 0.55; 95% CI, 0.46-0.66; P < .001), and patients with 5 or more LNs excised had a survival benefit over patients with 1 to 4 LNs removed (0.63; 0.40-0.96; P = .03). Lymph node excision improved survival in patients with T2 lesions (0.42; 0.33-0.53; P < .001 for patients with 1-4 LNs excised). CONCLUSION Extended surgical resection, LN excision, or both may improve survival in certain patients with incidentally discovered gallbladder cancer.

Evaluation of recent trends in cancer mortality and incidence among blacks

Recent trends in the cancer incidence, mortality, and 5‐year survival rate for the black population were evaluated using the available national data up to 1981. Blacks have the highest overall age‐adjusted cancer rates in both incidence and mortality of any US population group. The overall cancer incidence rates for blacks rose 17%, while for whites it increased 13% from 1969 to 1981. The rate in black men has increased 22.9%, while the rate in black women has increased 13.1%. The overall increase is the result of increases in cancers of the lung, prostate, colon‐rectum, and esophagus. The age‐specific incidence of lung cancer reflects the decrease of its incidence in those between 20 and 40 years of age because of the change in smoking habits after the Surgeon Generals report on smoking. The overall cancer mortality rates for blacks increased 39% during the period. Lung cancer had the highest mortality rate, having increased more than 77.8% since 1969. This trend greatly reflects the recent increase in lung cancer incidence among black women. The overall 5‐year cancer survival pattern for blacks was almost unchanged from 1973 to 1981, while whites had slightly higher survival rates during this period. However, blacks had substantial increases in survival rates for cancers of the esophagus and bladder during the period.

Treatment and Survival Outcome for Molecular Breast Cancer Subtypes in Black Women

Objective:To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes. Summary Background Data:Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables. Methods:Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu. Results:No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28–4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27–10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93–13.6, P = 0.06). Conclusions:The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.

Adenocarcinoma of the pancreas metastatic to the mandible.

I t is generally agreed today that metastatic tumors of the jaw occur more frequently than was formerly believed. These lesions are of great clinical importance, since their appearance in the jaw may be the first indication of an undiscovered malignancy which might exist in an unknown and distant primary site. This was true in the case that is being reported here. Among the carcinomas that have been known to metastasize to the jaws, the more common primary sites have been the breast, prostate, kidney, lung, thyroid gland, and gastrointestinal tract. The primary site of the tumor being reported here was the pancreas. Anderson1 states that only 2 per cent of all carcinomas are found in the pancreas, with the majority of these occurring in the head of the organ. Carcinoma of the tail of the pancreas is less commonly found. Clinically, carcinoma of the pancreas head is usually associated with obstruction of the common bile duct, accompanied by painless and ever-deepening jaundice, wasting, weakness, and clay-colored stools. Carcinoma of the tail of the pancreas usually is not accompanied by these symptoms. However, it is associated with earlier and more widespread extension and metastasis. Also, widespread venous thrombosis, especially of the lower extremities, and dccpseated pain may bc found in these cases2, 3

Management of external fistulas of the gastrointestinal tract

Abstract Twenty patients, fifteen female and five male, with external gastrointestinal tract fistulas were treated at Freedmens Hospital from 1965 to 1970. The locations of the fistulas were the colon, seven patients; ileum, six patients; jejunum, five patients; stomach, two patients. There were no duodenal fistulas. Operative injury secondary to lysis of adhesions for intestinal obstruction was the most common cause of these fistulas. There were six deaths. The proper management of complications of fistulas, that is, sepsis, malnutrition, skin excoriation, and fluid and electrolyte imbalance, is discussed. The proper timing of operative correction is emphasized noting that, as a rule, fistulas involving the upper small intestine require early surgery whereas lower small bowel and colonic fistulas may be treated successfully by nonsurgical means.