Timing of radiation therapy, lymph node retrieval, and survival in rectal cancer.

BACKGROUND: Lymph node retrieval is an independent prognostic factor for survival in rectal cancer. Preoperative radiotherapy has been shown to impact the number of lymph nodes retrieved. OBJECTIVE: This study aimed to analyze colorectal cancer-specific mortality and overall mortality associated with the number of lymph nodes retrieved in relation to use and timing of radiotherapy. DESIGN: This study was designed as a retrospective analysis. SETTINGS: Analysis of the California Cancer Registry was conducted. PATIENTS: Patients with rectal cancer from 1994 to 2006 with a follow-up until January 2008 were included. MAIN OUTCOME MEASURES: The number of lymph nodes (1-3, 4-6, 7-11, ≥ 12) stratified by stage (I, II, and III) was analyzed based on radiotherapy status (no radiotherapy, preoperative radiotherapy, and postoperative radiotherapy). Multivariate colorectal cancer-specific survival and overall mortality analyses were performed using Cox proportional-hazard ratios. RESULTS: A total of 17,670 incident cases of stage I, II, and III rectal cancer were identified. The number of lymph nodes retrieved in cases receiving preoperative radiotherapy was lower than others. In stage II cases receiving preoperative radiotherapy, retrieval of 7 to 11 lymph nodes (compared with 0 lymph nodes retrieved as a reference) reached the nadir of colorectal cancer-specific mortality benefit (HR = 0.39, 95% CI, 0.28-0.56) and overall mortality (HR = 0.62, 95% CI, 0.48-0.80). In stage II cases with no radiotherapy or postoperative radiotherapy, retrieval of ≥ 12 lymph nodes remained the strongest prognosticator of colorectal cancer-specific mortality (HR = 0.34, 95% CI, 0.25-0.46; HR = 0.36, 95% CI, 0.24-0.53 respectively). LIMITATIONS: : The California Cancer Registry does not include radiation dose and duration, chemotherapy type and dosage, margin status and surgeon characteristics, and stated reasons for lower number of lymph nodes retrieved or patient-related factors. In addition, no central pathology laboratory was used. CONCLUSIONS: In stage II rectal cancer cases receiving preoperative radiotherapy vs either postoperative or no radiotherapy, a lower threshold of lymph node retrieval may be sufficient to evaluate prognosis and to guide further therapy.

Autoantibody approach for serum-based detection of head and neck cancer.

Currently, no effective tool exists for screening or early diagnosis of head and neck squamous cell carcinoma (HNSCC). Here, we describe an approach for cancer detection based on analysis of patterns of serum immunoreactivity against a panel of biomarkers selected using microarray-based serologic profiling and specialized bioinformatics. We biopanned phage display libraries derived from three different HNSCC tissues to generate 5,133 selectively cloned tumor antigens. Based on their differential immunoreactivity on protein microarrays against serum immunoglobulins from 39 cancer and 41 control patients, we reduced the number of clones to 1,021. The performance of a neural network model (Multilayer Perceptron) for cancer classification on a data set of 80 HNSCC and 78 control samples was assessed using 10-fold cross-validation repeated 100 times. A panel of 130 clones was found to be adequate for building a classifier with sufficient sensitivity and specificity. Using these 130 markers on a completely new and independent set of 80 samples, an accuracy of 84.9% with sensitivity of 79.8% and specificity of 90.1% was achieved. Similar performance was achieved by reshuffling of the data set and by using other classification models. The performance of this classification approach represents a significant improvement over current diagnostic accuracy (sensitivity of 37% to 46% and specificity of 24%) in the primary care setting. The results shown here are promising and show the potential use of this approach toward eventual development of diagnostic assay with sufficient sensitivity and specificity suitable for detection of early-stage HNSCC in high-risk populations.

Factors associated with noncompliance to treatment with positive airway pressure.

OBJECTIVE: To identify risk factors that may predispose patients with a diagnosis of obstructive sleep apnea (OSA) to fail treatment with positive airway pressure (PAP) owing to noncompliance. DESIGN: Retrospective medical chart review. SETTING: Academic tertiary care center. PATIENTS: Patients who underwent polysomnography during 2 periods: from March 1999 to July 2001 and from March 2003 to December 2003. MAIN OUTCOME MEASURES: Of the 949 patients identified, only 131 patients had complete medical and follow-up records that were adequate for analysis of compliance. Compliance was defined as using PAP for at least 4 hours per night on 70% of the nights monitored. We used chi(2) and logistic regression analyses to assess correlations among PAP compliance and various patient variables as well as among sleep and titration study parameters. RESULTS: Of the 131 patients analyzed, 48 patients (37%) were noncompliant with PAP therapy. A statistically significant correlation was found between a low apnea-hypopnea index (AHI) and PAP noncompliance (P = .004). CONCLUSIONS: In this study, a low AHI was identified as a risk factor for noncompliance with PAP treatment. Therefore, patients with OSA and with a low AHI may warrant closer follow-up to allow early identification of PAP treatment failure owing to noncompliance and to allow timely institution of other treatment modalities, such as surgery.

Treatment compliance in patients lost to follow-up after polysomnography.

OBJECTIVES: Studies on positive airway pressure (PAP) compliance typically focus only on patients who returned for follow-up. In this study, we examined patients who failed to follow-up after their initial polysomnogram (PSG) and PAP titration to determine their treatment status in terms of PAP usage. STUDY DESIGN: On retrospective chart review, we identified 57 patients who, based on PSG findings and symptoms, required the use of PAP but failed to follow-up after titration. Twenty-five of these patients were successfully contacted and agreed to an interview. RESULTS: Only 7 (28%) patients were using PAP on a regular basis. The remaining 18 (72%) patients were noncompliant. CONCLUSIONS: A significant proportion (24%) of OSA patients who required treatment with PAP were lost to follow-up after polysomnography. This group of patients has previously been ignored in the literature. We showed in this study that majority (72%) of these patients were not being treated adequately for OSA.

Inhibition of the yeast metal reductase heme protein fre1 by nitric oxide (NO): a model for inhibition of NADPH oxidase by NO.

Nitric oxide (NO) has been found to inhibit the actions of the transmembrane metal reductase Fre1 in the yeast Saccharomyces cerevisiae. This membrane-spanning heme protein is homologous to the gp91(PHOX) protein of the NADPH oxidase enzyme complex and is responsible for reducing extracellular oxidized metals (i.e., ferric and cupric ions) before high-affinity uptake. Consistent with its role in metal metabolism, inhibition of Fre1 by NO also inhibited yeast growth in low-iron medium. Inhibition by NO was found to be O(2)-dependent and irreversible. Further examination of the chemistry responsible for activity loss shows that the generation of N(2)O(3) via NO-O(2) chemistry was responsible for the activity loss, possibly via nitrosation of the protein followed by loss of the heme prosthetic group.

Inherent redox properties of diesel exhaust particles: catalysis of the generation of reactive oxygen species by biological reductants.

The toxicity of diesel exhaust particles (DEP) can be due to the particle itself, extractable components, or both. Many studies focus on the biological properties of DEP-extractable components although it is possible that chemical properties inherent to the DEP itself can lead to toxicity. Thus, an examination of the chemistry inherent to DEP was carried out. Herein, we report that DEP are capable of catalyzing the consumption of O2 (monitored using a Clarke electrode) by ascorbate and thiols leading to the generation of reactive oxygen species. Consistent with the idea that DEP are capable of catalyzing the generation of reactive oxygen species, they were also found to catalyze DNA strand breakage via an O2- and reductant-dependent process. Significantly, extraction of DEP with either organic solvent (methylene chloride) or acid (aqueous HCl) did little to abrogate this chemistry. Finally, using electron paramagnetic spectrometry (EPR), DEP were found to have paramagnetic properties. The paramagnetic character of DEP may be important to their ability to catalyze the formation of reactive oxygen species and at least partially responsible for their toxicity. These findings indicate that studies that primarily consider or examine particle extracts as the toxic components of DEP may be insufficient in describing the toxicity associated with DEP exposure.

Colorectal Cancer Incidence Among Young Adults in California.

Purpose: Colorectal cancer (CRC) incidence has decreased over the past three decades, due largely to screening efforts. Relatively little is known about CRC incidence among the young adult (YA) population ages 20-39, as screening typically commences at age 50 for average-risk individuals. We examined CRC incidence with a focus on YAs in order to identify high-risk subgroups. Methods: We analyzed 231,544 incident CRC cases from 1988-2009 (including 5617 YAs 20-39 years of age) from the California Cancer Registry. We assessed age-specific incidence rates by race/ethnicity, gender, and colorectal tumor location, and calculated the biannual percent change (BAPC) to monitor change in incidence over the 22-year study period. Results: The absolute incidence of CRC per 100,000 was low among YAs 20-29 and 30-39 years old (ranging from 0.7 per 100,000 among Hispanic and African American females aged 20-29 up to 5.0 per 100,000 among Asian/Pacific Islander males aged 30-39). However, we observed increasing CRC incidence rates over time among both males and females in the YA population, particularly for distal colon cancer in Hispanic females aged 20-29 (BAPC=+15.9%; p<0.042). Conclusion: The absolute incidence of CRC remains far lower for YAs than among adults aged 50 and over. However, CRC incidence is increasing among young adults, in contrast to the decreasing rates observed for adults in the screened population (aged 50 and above). More research is needed to better characterize YAs at increased risk for CRC.

Mortality risk after preoperative versus postoperative chemotherapy and radiotherapy in lymph node-positive rectal cancer.

INTRODUCTION: Persistent lymph node-positive disease after preoperative radiotherapy for rectal cancer is associated with adverse outcomes. We quantified mortality risks of persistent pathologic lymph nodes in lymph node-positive rectal cancer patients treated with preoperative versus postoperative chemoradiation. METHODS: This was a retrospective population-based analysis of 2,038 patients with stage III rectal cancer diagnosed 1994-2005 with follow-up through 2007 using data from the California Cancer Registry. Survival estimates were generated using the Kaplan-Meier method. Multivariate cancer-specific and overall mortality analyses were performed using Cox proportional hazard ratios with adjustment for age, gender, race/ethnicity, tumor grade, T stage, N stage, socioeconomic status, and time period (1994-1997, 1998-2001, and 2002-2005). RESULTS: Overall survival was higher among lymph node-positive patients receiving postoperative chemoradiation compared to lymph node-positive patients receiving preoperative chemoradiation (median overall survival = 87 versus 62 months, P = 0.0002). In adjusted analyses, patients with persistent lymph node-positive disease after preoperative chemoradiation treatment had increased overall (HR = 1.69; 95 % CI, 1.42-2.01) and CRC-specific (HR = 1.78; 95 % CI, 1.44-2.19) mortality risk compared to lymph node-positive disease after postoperative chemoradiation treatment. CONCLUSIONS: Stage III rectal cancer patients with persistent pathologic lymph nodes after preoperative chemoradiation represent a high-risk group, with higher mortality than those treated with postoperative chemoradiation.