The epidemiology and survival of extrapulmonary small cell carcinoma in South East England, 1970–2004

<p>Abstract</p> <p>Background</p> <p>Extrapulmonary small cell carcinoma (EPSCC) is a rare cancer and few studies describe its epidemiology. Our objectives were to compare the incidence and survival of EPSCC in South East England with small cell carcinoma of the lung (SCLC), to determine the most common anatomical presenting sites for EPSCC and to compare survival in EPSCC by disease stage and site of diagnosis.</p> <p>Methods</p> <p>We used data from the Thames Cancer Registry database for South East England between 1970 and 2004 to determine the incidence, most common anatomical sites, and survival by site, and stage of EPSCC. 1618 patients registered with EPSCC were identified. We calculated the age-standardised incidence rate for EPSCC using the European standard population and compared this to that for SCLC. We calculated survival using the Kaplan-Meier method for EPSCC and SCLC, and reported 3-year survival for different EPSCC anatomical sites and disease stages.</p> <p>Results</p> <p>The incidence of EPSCC was much lower than for SCLC, similar in males and females, and stable throughout the study period, with incidence rates of 0.45 per 100,000 in males and 0.37 in females during 2000–2004. In general, patients with EPSCC had a better 3-year survival (19%) than SCLC (5%). The most common anatomical sites for EPSCC were oesophagus (18%), other gastrointestinal (15%), genitourinary (20%), head and neck (11%), and breast (10%). Breast EPSCC had the best 3-year survival (60%) and gastrointestinal EPSCC the worst (7%).</p> <p>Conclusion</p> <p>This study suggests that EPSCC has a stable incidence and confirms that it presents widely, but most commonly in the oesophagus and breast. Site and extent of disease influence survival, with breast EPSCC having the best prognosis. Further studies using standardised diagnosis, prospective case registers for uncommon diseases and European cancer registries are needed to understand this disease.</p

Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality.

Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP) negatively influences outcomes. Following CLP mice were randomized to receive the antibiotic imipenem-cilastatin (25mg/kg) in dextrose 5% in Lactated Ringer's solution every 12 hours for either three or five days. Serial monitoring over 28 days included body weight, temperature, pulse oximetry, and facial vein sampling for hematological analysis and glucose. A separate group of mice were euthanized on post-CLP day 5 to measure cytokines and peritoneal bacterial counts. The first study examined no antimicrobial therapy and demonstrated that antibiotics significantly improved survival compared to fluids only (p = 0.004). We next tested imipenem-cilastatin therapy for 3 days versus 5 days. Body weight, temperature, glucose, and pulse oximetry measurements remained generally consistent between both groups as did the hematological profile. Pro-inflammatory plasma cytokines were comparable between both groups for IL-6, IL-1β, MIP-2 and anti-inflammatory cytokines IL-10, and TNF SRI. At 5 days post-CLP, i.e. 2 days after the termination of antibiotics in the 3 day group, there were no differences in the number of peritoneal bacteria. Importantly, shortening the course of antibiotics by 40% (from 5 days to 3 days) did not decrease survival. Our results indicate that reducing the duration of broad-spectrum antibiotics in murine sepsis did not increase inflammation or mortality

Survival Proportions.

<p>There was no significant survival difference between the 5 days versus 3 days treatment group following CLP. N = 27–28 mice per group. There is also no statistically significant difference between the survival of the 5 day mice in this group and the comparable group in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163005#pone.0163005.g001" target="_blank">Fig 1</a>.</p

Physiological and glucose measurements 5 days post-CLP.

<p>Physiological and glucose measurements 5 days post-CLP.</p

Hematologic changes.

<p>The shorter 3 day antibiotic treatment did not significantly change peripheral blood measurements in septic mice compared to 5 days of treatment. Five day treatment mice showed elevations of WBC, neutrophil, and lymphocyte counts starting at day 7 which normalized by day 28. Five day treatment had significantly higher WBC and neutrophil counts only at 14 and 21 days post-CLP, respectively. The WBC and neutrophil count remained elevated at day 28 compared to the pre-CLP values, probably due to the ongoing stress of the infection. All other hematologic changes returned to pre-CLP (day 0) levels by day 28. Data expressed as mean ± SEM, n = 16–18 per group, *<i>p</i> < .05 **<i>p</i> < .01.</p

Antibiotic therapy used in murine cecal ligation and puncture studies.

<p>Antibiotic therapy used in murine cecal ligation and puncture studies.</p

Peritoneal Lavage bacterial CFUs day 5 post-CLP.

<p>Mice were euthanized at day 5 post-CLP and the peritoneum lavaged and cultured. There were no significant differences in the number of bacterial colony forming units. Individual data points are show as well as the mean ± SEM, n = 6–7 mice per group.</p

Pro-inflammatory and anti-inflammatory cytokines at day 1 post-CLP.

<p>Pro-inflammatory and anti-inflammatory cytokines at day 1 post-CLP.</p