High-dose radiotherapy in trimodality treatment of Pancoast tumors results in high pathologic complete response rates and excellent long-term survival

OBJECTIVE: We sought to study the clinical characteristics and outcomes of patients treated with a surgery-inclusive multimodality approach for Pancoast tumors. METHODS: Clinical records of patients with Pancoast lung cancer who were enrolled for multimodality treatment between 1993 and 2003 at our institution were reviewed retrospectively. RESULTS: Thirty-six patients completed neodjuvant chemoradiation followed by en bloc surgical resection, whereas one patient received high-dose radiation alone followed by surgical intervention. There were 22 men and 15 women. Thirty-four lobectomies and 3 pneumonectomies were performed. Pretreatment non-small cell lung cancer stages were IIB, IIIA, IIIB, and IV (presenting with solitary brain metastasis) in 18, 8, 6, and 5 cases, respectively. R0 resection was achieved in 36 (97.3%) patients. Operative mortality was 2.7% (n = 1). High-dose radiotherapy was successfully tolerated in all but 1 patient. Mean total radiation dose was 56.9 Gy. Pathologic complete response was found in 40.5% (n = 15) of patients. Recurrences were found in 50% (n = 18) of patients. Brain metastasis was the most common recurrence (n = 9), followed by other distant recurrences (n = 4) and local recurrences (n = 5). Median survival time for the group is 2.6 years, and median survival time (pathologic complete response) is 7.8 years. It is noteworthy that median survival time of patients with positive pretreatment lymph nodes (12 patients) was not reached. CONCLUSIONS: Surgical resection of Pancoast tumors after neoadjuvant high-dose radiation and chemotherapy can be safely performed. High-dose radiation in trimodality treatment is well tolerated and might be beneficial. Similar to other studies, late central nervous system relapse is problematic and indicates a need for assessing the role of prophylactic cranial irradiation in this disease.     

Safety of uncrossmatched type-O red cells for resuscitation from hemorrhagic shock

BACKGROUND: Uncrossmatched type-O packed red blood cells (UORBC) are recommended for immediate transfusion in hemorrhaging trauma patients. The potential for alloimmunization with this technique is controversial, and has been reported to be as high as 80%. We examined a 1-year experience with UORBC transfusion to determine the incidence of allergic reaction and alloimmunization. METHODS: Blood Bank and Trauma Registry databases for the year 2000 were linked to determine the incidence of UORBC use and the characteristics of patients, including the incidence of transfusion reactions and seroconversion of Rh-patients. Ten units of type-O, Rh+ blood (and two units of O-blood for women of childbearing age) were available for immediate transfusion, 30 to 45 minutes sooner than type-specific or crossmatched red blood cells. UORBC were administered to any patient with signs of severe hemorrhagic shock, at the discretion of the attending physician. RESULTS: In all, 480 trauma patients (out of 5,623 admitted) received transfusions of RBC, totaling 5,203 units. Five hundred eighty-one units of UORBC were given to 161 patients. Average Injury Severity Score in the UORBC cohort was 33.8. Patients receiving UORBC received an average of 16.9 total units of red blood cells, 14 units of plasma, and 10 units of platelets. Seventy-three patients died (45%). There were no acute hemolytic transfusion reactions observed in the patients who received UORBC. Four Rh-women received UORBC, all O-. Ten Rh-men received O+ blood, and only one developed antibodies to the Rh antigen. CONCLUSION: The need for UORBC is associated with significant injury and the need for subsequent massive transfusion. In this largest reported trauma series, the use of UORBC enabled rapid administration of red cells to hemorrhaging patients, without discernible risk for transfusion-related complications. The rate of seroconversion of Rh-patients is lower than reported in the literature, perhaps due to immune suppression associated with hemorrhagic shock.     

Epidemiology of capsular and surface polysaccharide in Staphylococcus aureus infections complicated by bacteraemia

Staphylococcus aureus is a leading cause of serious hospital- and community-acquired infections. The discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has allowed the development of vaccines and passive protective immunity. We have studied patient characteristics, infection characteristics and the surface and capsular polysaccharide serotype distribution in patients with S. aureus infections complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and 2000. Nine hundred and ninety-three blood cultures from 331 patients were positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had end-stage renal failure, and 23% were injection drug users. Forty-two percent of infections were caused by methicillin-resistant strains (MRSA), and 60% were acquired during hospitalization. Serotyping of the first available isolate per patient (N=234 isolates) using polyclonal antibodies showed three major phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336 polysaccharide. MRSA isolates were significantly more likely to be T5 than methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.     

DEOXYRIBONUCLEASE IV: A NEW EXONUCLEASE FROM MAMMALIAN TISSUES

An exonuclease which specifically degrades double-standard DNA has been isolated from rabbit tissues. The enzyme has an approximate molecular weight of 42,000, requires a divalent metal ion as cofactor, and attacks DNA at the 5'-terminal ends, thereby liberating 5'-mononucleotides. It degrades several synthetic polydeoxynucleotides of single repeating base sequences more rapidly than DNA from natural sources. The specificity of this mammalian enzyme resembles that of several microbial enzymes (phage lambda exonuclease and DNA polymerase) which appear to be required for repair and recombination of DNA.     

Structure of Concanavalin A at 4 ? Resolution

Concanavalin A, a phytohemagglutinin isolated from the jack bean, crystallizes at pH 6.8 in the orthorhombic space group 1222 with a = 89.9, b = 87.2, and c = 63.1 A. We have analyzed x-ray diffraction intensity data to 4 A resolution on native concanavalin A and five heavy-metal derivatives: lead, mersalyl, chloroplatinate, uranyl, and o-mercuri-p-nitrophenol. Heavy-atom positions, occupancies, and isotropic thermal parameters have been refined by least-squares methods.The electron density maps clearly show the molecular shape and the packing of the concanavalin A molecules. The asymmetric unit (mol wt 27,000) forms an elliptical dome or "gumdrop" with a base of approximately 46 x 26 A and a height of 42 A. The subunits are paired across 2-fold axes parallel to the c-axis to form dimers. The dimers are in turn paired across points of D(2) symmetry to form tetramers of roughly tetrahedral shape. Each unit has a depression located on the surface which could be the site of saccharide binding. In many regions we have been able to trace the course of the polypeptide chain.