Differences and similarities in the immune response of septic patients with acute surgical abdomen compared with septic sydrome other infectious etiology

Former studies of our group have shown that the innate and adaptiveimmune status may differ in relation with the causative infection. To this sameend, it was investigated if kinetics of circulating lipopolysaccharide (LPS)leading to inflammatory response may differ. Blood was sampled from 189patients with sepsis and 206 with severe sepsis/shock starting 24 hours fromadvent of sepsis and repeating on day 3. Serum LPS was measured byLimulus Amebocyte Lysate (LAL) assay. From 59 patients, circulatingmonocytes were isolated and incubated in the absence/presence of LPS.Concentrations of tumour necrosis factor alpha (TNFα) were measured insupernatants by an enzyme immunoassay. In either category of severity,circulating LPS was greater among sufferers from primary Gram-negativebacteraemia (BSI) and from community-acquired pneumonia (CAP) thansufferers from other underlying infections. LPS were greater among patientswith BSI compared to patients with secondary Gram negative bacteraemia and patients without bacteraemia. Greater decrease of circulating LPS over48 hours was recorded for survivors compared to non survivors only withinsufferers from BSI and CAP. Significant endotoxemia was considered forpatients with serum LPS within the upper quartile of distribution; theirmonocytes were less potent for release of TNFα. It is concluded thatendotoxemia in sepsis varies greatly with the underlying infection; this isrelated with immunoparalysis of monocytes with implications on final outcome

Induction chemotherapy followed by concurrent chemoradiation in advanced squamous cell carcinoma of the head and neck: final results from a phase II study with docetaxel, cisplatin and 5-fluorouracil with a four-year follow-up

Encouraging results have recently been reported in patients (pts) with locally advanced unresectable, squamous cell carcinoma of the head and neck (SCCHN) when induction chemotherapy (IC) is used and followed by radiotherapy (RT). The present study assessed the therapeutic response of an aggressive regimen consisting of clocetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-Fu) as IC and concurrent with RT in pts with locally advanced (stages III and IV) SCCHN. 42 pts (35 male and 7 female) with a mean age of 58 years suffering from stages III and IV (Mo) SCCHN were included to this organ preservation phase II clinical trial. The site of the primary tumors was the anterior mouth in 9 pts, base of tongue and oropharynx in 12, middle third of the face in 8 and larynx in 13. The performance status of the pts was 0-1 according to WHO and above 80% according to Karnofsky classification. IC consisted of TXT (40 mg/m(2)), CDDP (40 mg/m(2)) and 5-Fu (350 mg/m2) every two weeks (wks) for a total of four courses and repeated, coupled with RT (66-68 cGys total dose fractionated at 200 Gy per day, 5 days a week), for up to seven wks. In total, pts received eight courses of chemotherapy (CT) at the end of RT treatment. Pts were evaluated at the end of IC, after RT and every six wks thereafter. 41 pts were eligible for evaluation after IC (one died from myocardial infarction) and 39 after completion of treatment (two died during RT). Statistical multivariate analysis was performed using SPSS (11) package. Complications from IC and RT were evaluated according to WHO criteria and included mucositis Grade (Gr) IV in 10% of the pts, Gr III in 50%, Gr II in 20%. Anemia presented in 40% of the pts with Gr II, 40% with Gr I, neutropenia 17% with Gr IV, 20% with Gr III, 30% with Gr II, thrombocytopenia 3% with Gr III, 10% with Gr I and xerostomia up to Gr II in 70% of the pts. The response rate (RR) after IC was complete response (CR) for 10 pts (24.4%), partial response (PR) for 22 (53.7%) and no response (NR) for 9 (21.9%). At the end of the treatment the RR in the intention-to-treat population were CR for 25 pts (64.1%), and PR for 14 (35.9%). Follow up ranges from 18 to 56 months (mts). 14 pts died during follow-up time. The mean survival time is 41 mts and the median 40. 2 pts with CR developed local recurrence and two distant metastases, whereas all pts with PR developed progressive disease (PD) and all but two are dead from disease. It is evident from this phase II study that TXT-CDDP-5Fu based IC followed by the same regimen coupled with RT improves local control. Pts that showed CR after IC continued to maintain disease status during RT (P-value = 0.0181). In pts with SD concurrent RT did not alter dramatically disease outcome. Patients who showed complete response after both IC and RT presented a four-year survival rate of 74% compared to a 30% to partial responders (P-value = 0.0001). Results are encouraging and further study of the toxicity and follow-up is needed to validate treatment effectiveness. (c) 2005 Elsevier Ltd. All rights reserved