Prognostic Implications of Molecular and Immunohistochemical Profiles of the Rb and p53 Cell Cycle Regulatory Pathways in Primary Non–Small Cell Lung Carcinoma
Abstract Purpose: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non–small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. Experimental Design: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non–small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. Results: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21Waf1 overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). Conclusions: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.
At the Nexus of Academic and Social Change: The School for the Science of Health Care Delivery
Abstract Nine consecutive patients underwent surgery for liver and lung metastases from colorectal cancer (Dukes' stage B in five, C in one and ‘D’ in three) between 1980 and 1991. A total of 21 procedures were performed: 16 thoracotomies with six lung lobectomies and 17 lung wedge resections, ten laparotomies with nine hepatectomies and six liver wedge resections. No operative or hospital deaths occurred and the mean(s.d.) postoperative hospital stay was 10(7) days per procedure. Perioperative blood transfusions for all nine patients amounted to a total of 7 units. The median survival after completion of liver and lung surgery was 27 (range 10–62) months. Median survival from resection of the first liver or lung metastasis was 30 (range 12–62) months and from excision of the primary colorectal tumour 46 (range 30–78) months. Two patients were alive and well 11 and 62 months after liver and lung resections; seven have died with metastases. This controversial aggressive treatment resulted in longer survival times than most alternative therapies in these highly selected and well motivated young patients, with no hospital mortality and only moderate morbidity.
AbstractThe cause of splenic artery aneurysms and the indications for their treatment remain controversial. Splenic artery aneurysms occur more frequently in women and are associated with pregnancy and multiparity. Whether arteriosclerosis is the cause of the aneurysm or is a secondary phenomenon is unknown. Patients not treated do well, especially if the aneurysm is less than 2 cm in diameter. The rate of rupture is approximately 3%, and it appears to be decreasing as more patients are found to have this type of aneurysm. The mortality rate for ruptured splenic artery aneurysm is greatly increased if the patient is pregnant. Indications for removal include presence of symptoms, pregnancy or plan to become pregnant, increasing size, and a diameter of 2 cm or greater. Depending on the medical condition of the patient, aneurysms that are less than 2 cm in diameter can be removed electively, or they can be left and the patient followed closely. The risk of elective removal is extremely low and has minimal morbidity. In the treatment of this type of aneurysm, the spleen should be preserved if possible; splenectomy is reserved for those aneurysms found in the hilus of the spleen or during emergency situations.