Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome

Preoperative radiation (RT) and chemotherapy improve outcome in patients with locally advanced rectal adenocarcinoma and, therefore, have been used increasingly in patient management. The histopathologic alterations in postirradiated rectal adenocarcinoma and their prognostic significance have not been fully characterized. In this study, detailed analyses of morphologic alterations of stromal and tumor cells were performed in a series of 66 posttreatment rectal carcinomas, and the pathologic findings were correlated with long-term outcome. All tumors were locally advanced, with a bulky and/or tethered tumor or endorectal ultrasound or magnetic resonance imaging evidence of T3-4 and / or N1 disease. All patients were treated at one institution with preoperative RT to the pelvis (at least 4500 cGy) with or without concurrent 5-fluorouracil (5-FU)-based chemotherapy 4 to 7 weeks prior to surgical resection. Pathologic assessment showed some treatment response in all patients. Nine patients (13.4%) had complete response, and 8 (11.9%) had near-complete response (> 95% of the tumor replaced by fibroinflammatory tissue). Salient morphologic features included marked fibrosis with or without prominent inflammatory cells replacing neoplastic glands; lack of active tumor necrosis; increased mucin production and mucin pools; marked cytoplasmic eosinophilia, often in combination with marked nuclear atypia but without active mitoses in tumor cells showing treatment effect; endocrine tumor phenotype; and retention of mucosal adenoma in the presence of tumor regression within the bowel wall. With a median follow-up of 69 months, the estimated 5-year recurrence-free survival (RFS) for the entire group was 79%. By univariate analysis, the residual tumor stage (P < 0.05) and reduction of pretreatment T stage (P = 0.002) significantly correlated with RFS, as did pN stage (P = 0.002) and lymphovascular invasion (P = 0.008). The extent of treatment response did not correlate with RFS (P = 0.4). However, patients with a treatment response > or = 95% seemed to fare better than those with a treatment response < 95% (marginally significant difference in RFS, P = 0.057). Univariate and multivariate analyses identified the following morphologic patterns that were significantly associated with a reduced RFS independent of other risk factors: a fibrotic-type stromal response with minimal inflammatory infiltrates (P = 0.001) and absence of surface ulceration (P = 0.026). Our study represents the first detailed morphologic assessment of rectal carcinomas that have been subjected to long course preoperative RT and chemotherapy. Our results demonstrate distinct morphologic features in treated rectal carcinomas that are prognostically relevant.     

Factors influencing length of hospital stay in community-acquired pneumonia: a study in 27 community hospitals

We did a retrospective study of 1920 episodes of community-acquired pneumonia (CAP) in 27 community hospitals and analysed inter-hospital variability in length of hospital stay (LOS), mortality and readmission rates. The overall adjusted LOS (mean+/-S.D.) was 10.0+/-9.8 days. LOS increased according to the Pneumonia Severity Index (PSI) risk class: 7.3 days for class I to 11.3 days for class V (P<0.001). In a multiple regression model, LOS increased (P<0.001) according to the hospital (inter-hospital variability), PSI risk class, complications during hospitalization, admission to ICU, need of oxygen and transfer to a nursing home. Hospitals with shorter LOS did not show an increased readmission rate (adjusted OR 1.02, 95% CI 0.51-2.03, P = 0.97) and post-discharge mortality (adjusted OR 1.20, 95% CI 0.70-2.05, P=0.51). There are significant inter-hospital variations in LOS in patients with CAP which are related to differences in clinical management. The reduction of these differences will further improve efficiency and quality of care.     

Bacteriophages and diffusion of beta-lactamase genes

We evaluated the presence of various Beta-lactamase genes within the bacteriophages in sewage. Results showed the occurrence of phage particles carrying sequences of bla(OXA-2), bla(PSE-1) or bla(PSE-4) and bla(PSE)-type genes. Phages may contribute to the spread of some Beta-lactamase genes.     

Etilefrine use in the management of post-operative chyle leaks in thoracic surgery

Etilefrine, a sympathomimetic drug, was used 11 times in 10 patients with thoracic (n=8) or abdominal (n=2) chyle leak occurring after thoracic surgical procedures. It was given as a 4.2-5 mg/h intravenous infusion. During the 11 etilefrine administrations, three patients had total parenteral nutrition, three had enteral nutrition, three had oral fat-free diet and medium-chain triglyceride supplementation, and two were fed orally without restriction. Daily chyle flow output decreased in all but one patient who was reoperated. Chyle flow output did not decrease relevantly in one patient who was reoperated. Chylothorax recurred after reoperation and etilefrine then induced significant output decrease. In another patient, etilefrine was stopped despite significant output reduction because of interactions with other sympathomimetic drugs used for heart failure. The mean etilefrine treatment duration was 6.4 days (range 4-7). The mean daily output was from 740 ml before etilefrine infusion to 183 ml on the seventh day of etilefrine use. By inducing contraction of the smooth muscle fibres present in the wall of the main thoracic chyle ducts, etilefrine can be considered as a useful adjunct in the management of post-operative chyle leak.     

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01).This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.     

The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis

We recently isolated the r-PTPeta gene, which encodes a receptor-type tyrosine phosphatase protein that suppresses the neoplastic phenotype of retrovirally transformed rat thyroid cells. The human homologue gene PTPRJ/DEP-1 is deleted in various tumors. Moreover, the Gln276Pro polymorphism, located in the extracellular region of the gene, seems to play a critical role in susceptibility to some human neoplasias. Here we report the loss of heterozygosity (LOH) of PTPRJ in 11/76 (14.5%) informative thyroid tumors (including adenomas and carcinomas). We also looked for the Gln276Pro, Arg326Gln and Asp872Glu polymorphisms in exons 5, 6 and 13 of PTPRJ in 88 patients with thyroid tumors and in 54 healthy individuals. We found that the PTPRJ genotypes homozygous for the Gln276Pro and Arg326Gln polymorphisms, and the Asp872 allele were more frequent in thyroid carcinoma patients than in healthy individuals (P=0.032). In addition, PTPRJ LOH was more frequent in thyroid carcinomas of heterozygotes for Gln276Pro and Arg326Gln compared with homozygotes (P=0.006). This suggests that the presence of hemizygosity for these polymorphisms in the tumor facilitates tumor progression. These results indicate that the genotypic profile of PTPRJ affects susceptibility to thyroid carcinomas, and that allelic loss of this gene is involved in thyroid carcinogenesis.     

Surgical issues in rectal cancer: a 2004 update

Rectal cancer is a major health concern in the United States, with an estimated 40,570 new cases diagnosed in 2004. There are 4 major goals in the treatment of a patient with rectal cancer: local control; long-term survival; preservation of anal sphincter, bladder, and sexual function; and maintenance or improvement in quality of life. Recent advances have been made in preoperative staging, local and radical surgical therapy, the importance of distal and circumferential resection margins, postoperative preservation of the anal sphincter mechanism and genitourinary function, and the role of laparoscopy in the treatment of these patients. Our aim is to outline some of the important surgical issues surrounding the management of patients with early-stage (T1/T2 N0) or locally advanced (T3/T4 and/or N1) rectal cancer.