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Background: There is still the need to optimize adjuvant treatment of colon cancer (CC). Standard adjuvant chemotherapy using 5-fluorouracil (FU) and folinic acid (FA) was compared with a combination including irinotecan (Folfiri). The aim of the present report was to analyze overall survival (OS) after long-term follow-up, to summarize final recurrence rates and toxicity data, and to identify possible clinical and pathological factors associated with prognosis. Methods: Patients (CC stage IIb and III) were randomized to a 6-month treatment with FUFA or Folfiri. The trial was closed after 275 of 588 planned patients, 269 of which were included in the intention-to-treat analysis. Results: 133 and 136 patients received FUFA and Folfiri, respectively. Adjuvant therapy was not completed for 16 FUFA (12.0%) and 44 Folfiri (32.4%) patients. Toxicities grade III and IV were observed in 17 (12.8%) patients treated with FUFA and in 50 (36.8%) patients treated with Folfiri. Recurrences occurred in 46 of 133 (34.6%) and in 47 of 136 (34.6%) patients who received FUFA and Folfiri, respectively. 5-year OS rates were 69.9% (95% confidence interval (CI): 61.2-77.1) for FUFA and 72.7% (95% CI: 63.9-79.8) for Folfiri. OS was associated with tumor grading (1 & 2 vs. 3), tumor sub-stage (II vs. IIIa vs. IIIb vs. IIIc), and tumor location (left vs. right colon). Conclusion: Folfiri cannot be generally recommended for adjuvant chemotherapy of CC. Besides tumor grading and sub-staging, prognosis of CC may depend on tumor location. Left-sided tumors had a significantly better prognosis irrespective of treatment.

Colorectal cancer (CRC) is the third most common cancer worldwide. A diagnosis at early stages with enhanced screening methods is vital as metastases and recurrences increase mortality. The aim of this study was to analyze the tumor markers CEA and CA19-9 combined in correlation with diagnostics and prognosis. Therefore, 1487 patients with CRC who were diagnosed and treated between 2000 and 2015 at the University Hospital Ulm, Germany, were retrospectively evaluated. Overall and recurrence-free survival was analyzed in association with preoperative CEA and CA19-9 separately and combined and a multivariate analysis was performed. The 5-year overall survival was significantly shorter in patients with a CEA or CA19-9 level ≥200 compared to patients with an increased, but &lt, 200, or normal level (CEA: 69%/44%/7%, CA19-9: 66%/38%/8%). Patients with both tumor markers increased also showed a remarkably shorter 5-year survival rate (CEA+/CA19-9+: 23%). The multivariate analysis emphasizes these results (p-value &lt, 0.0001). Patients with both tumor markers elevated had the shortest 5-year recurrence-free survival rate, followed by patients with either CEA or CA19-9 elevated (CEA-/CA19-9-: 79%, CEA+/CA19-9, CEA-/CA19-9+: 65%, CEA+/CA19-9+: 44%). In conclusion, measuring CEA and CA19-9 preoperatively in CRC patients is reasonable and could be useful as a prognostic factor.

With an increasing number of cancer survivors quality of life (QoL) becomes more and more important in the treatment of rectal cancer (RC). QoL after sphincter-preserving anterior resection (AR), however, was found nonsuperior to abdominoperineal resection. The aim of our study was to evaluate QoL after AR compared with colon cancer patients after right hemicolectomy (CC) and healthy lay persons without history of cancer (HL) in long-term follow-up.Consecutive alive RC patients (n = 293) who received an AR between 1998 and 2008 were included. CC patients (n = 201) and HL of the same age were used as a surgical and a nonsurgical control group, respectively. QoL was assessed using European Organization of Research and Treatment of Cancer questionnaires QLQ-C 30 and -CR 38.Questionnaires from 116 RC patients, 105 CC patients, and 103 HL were evaluable with a median time after surgery of 5 years. The global health status did not differ. Social functioning, future perspectives, and financial difficulties tended to poorer scores in the cancer groups. Physical functioning was better in RC and CC patients compared with HL. Defecation problems and diarrhea were more frequent in RC patients (P.05). An additional open question revealed a median stool frequency of 3, 2, and 1 per day for RC, CC, and HL, respectively. Defecation problems were more frequent in RC patients who received radiation therapy (P.05).Diarrhea and defecation problems impaired QoL after AR for RC, which was worsened after radiation therapy. To improve QoL of RC patients in the future, physicians have to focus on minimization of gastrointestinal side effects while optimizing surgical reconstruction.

BACKGROUND Since 2006 an assessment of the neurodevelopmental outcome of very low birth weight infants (VLBWI) at a corrected age of 2 years is mandatory for every perinatal centre in Germany. The aim of our study was to check how complete these assessments were performed in our population of infants born at our perinatal centre and receiving treatment within our local neonatal network. Furthermore, the data obtained will be used for prenatal consultations. Another objective was to identify risk factors for adverse neurodevelopmental outcomes. METHODS All VLBWI were invited for a follow-up exam using the Bayley Scales of Infant Development II (BSID-II) or III (BSID-III), or Griffiths Mental Developmental Scales) at 2 years corrected age. The results of children assessed by other institutions were collected. RESULTS 142 (69.3%) of the 205 VLBWI, born and finally discharged alive at the perinatal centre in Ulm were assessed at a median (minimum - maximum) corrected age of 23 (18-27) months. The BSID-II Psychomotor Development Index (PDI) 91 was (< 50-128) (n=115), the BSID-II Mental Development Index (MDI) was 87 (< 50-134) (n=96), BSID-III MDI 95 (60-112) (n=29) and the Griffiths Score was 93 (67-140) (n=17). Severe disability was diagnosed in 36 (25.4%) of the children studied. Gestational age and higher grade intraventricular haemorrhage were associated independently with severe disability. CONCLUSIONS It is very difficult to achieve a high rate of follow-up examinations in preterm infants

Adjuvant chemotherapy is recommended for stage III colon cancer. The aim of this study was to identify important prognostic factors among patients with colon cancer receiving adjuvant 5-FU-based treatment.Data sets of 855 colon cancer patients treated between 1992 and 1999 within a multicenter adjuvant trial comparing 5-FU modulation with folinic acid or interfereron-alpha were examined. Backward elimination in a proportional hazards model was used to identify prognostically relevant clinical and pathological factors.Tumor recurrence (p0.001), duration of adjuvant treatment (p0.001), tumor substage (p=0.004), age (p=0.005), grading (p=0.016), treatment-related toxicity (p=0.021), and treatment (p=0.031) were identified in descending order of importance as prognostic factors for overall survival.Adjuvant 5-FU-based treatment should be performed for at least 6months with a stepwise adjustment of 5-FU doses until toxicityWHO II. Substages should be reported separately and used for stratification in future trials due to their broad variation in outcome. In the future, this may result in adjuvant treatment of stage III colon cancer adjusted for the risk of substages.

Study design Experimental in vivo study. Objective The objective was to investigate the balance control in patients with acute QTF grade II whiplash injuries of the cervical spine. Summary of background data Tetra-ataxiametric posturography in chronic pain patients after whiplash injuries of the cervical spine has revealed an impaired regulation of balance. However, so far it is unclear if this is caused by the accident or other factors that are associated with the pain chronification process. Methods 40 patients with acute QTF grade II whiplash injuries and 40 healthy matched controls were examined on a posturography platform. The stability index ST Σ and the Fourier analysis FA Σ (0.10–1.00 Hz) were established for eight standing positions and sum scores were calculated. The pain index was established using a visual analog scale ranging from 0 to 100. A follow-up examination was conducted for the patients after 2 months. Results The patients with acute whiplash injuries of the cervical spine achieved significantly poorer results for both ST Σ and FA Σ than the healthy controls. There were no differences between the eight standing positions for both ST Σ and FA Σ . After 2 months, 17 patients had no change in the pain development, 21 patients showed an improvement in pain intensity and 2 patients had deteriorated. The subgroup of patients with improvement in pain intensity showed a significant improvement in balance control concerning the FA Σ compared to patients with unchanged pain intensity. Conclusion Patients with acute whiplash injuries have a reduced balance control as compared to matched controls. This study gives an indication that post-traumatic neck pain is associated with impairments of postural control.

Colorectal cancer is one leading cause of cancer-related death worldwide, and distant metastases determine an unfavorable prognosis. Surgical resection of colorectal liver metastases (CRLM) improves survival and provides the chance for cure. The aim of this study was to prospectively analyze the outcome of patients with CRLM in a population-based manner, and thereby, to compare the prognosis of patients undergoing resection with those receiving nonsurgical treatment. Moreover, we set out to identify and confirm important prognostic factors after resection of CRLM.We analyzed the outcome of 506 patients diagnosed with CRLM in our institution from 1996 to 2011. Survival and the impact of clinical and pathologic factors were analyzed by univariate analysis. Important independent prognostic factors were analyzed by multivariate analysis.The 5-year overall survival rate (5y-OSR) for patients receiving resection of CRLM (n = 152) was 46% (95% confidence interval (CI), 37%-54%) compared with a 5y-OSR of 6% (95% CI, 4%-9%) for patients treated nonsurgically (n = 354). There was no perioperative mortality. Multivariate analysis revealed, among other factors, good performance status of the patient (low American Society of Anesthesiologists score), the absence of extrahepatic metastases, 5 metastatic lesions, and a tumor-free resection margin (R0) as important, independent prognostic factors. Importantly, repeated hepatic resections of CRLM performed in 13 patients were associated with an excellent outcome (5y-OSR, 47%; 95% CI, 17%-72%).Surgical resection, which can be performed with tolerable site-effects, is the first choice for patients diagnosed with metachronous and synchronous CRLM. Of note, repeated resections should be advised in recurrent intrahepatic colorectal cancer whenever possible.

Thymidylate synthase (TS) is a key-enzyme for DNA synthesis and targeted by fluoropyrimidines (FPs). High TS ratios are associated with resistance to systemic FP-based chemotherapy. The aim of this study was to report the influence of TS ratios on primary tumour response to FP-based HAI and long-term follow-up of patients with isolated non-resectable liver tumours in part from a previously published study.Fifty-one consecutive patients with liver tumours receiving HAI with available tumour tissue for TS quantitation were studied between 1991 and 2001. Liver metastases were from colorectal origin in 41 patients and other primary sites in 6 patients. Four patients had primary liver cancers. Tumour tissue was obtained at laparotomy for the intraarterial infusion device implantation. TS mRNA quantitation was performed by RT-PCR using beta-actin as internal standard.The median TS ratio was 2.2 with high variation among tumours ranging from 0.1 to 27. Twenty-two out of 51 patients responded to HAI. The median TS ratio of the responders was 1.6 and more than two-fold lower than the ratio of the non-responders with 3.3 (p0.01). In the subgroup with TSor=3.0, 18 out of 29 patients responded. In the subgroup with TS3.0 only four out of 22 patients responded. No patients with very high TS ratiosor=4.5 ( n = 13) responded to HAI. Median survival was 20 months (range: 3-109). Patients with TS-ratiosor=3.0 showed, with 55%, a higher 2-year survival rate than patients with TS-ratios3.0 with 27%.TS seems to be a predictive and prognostic factor for patients with isolated non-resectable liver tumours receiving FP-based HAI. Patients with very high TS ratios do not seem to benefit from FP-based HAI.

Objectives. To examine whether early enteral iron supplementation (EI) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency (ID) in infants with a birth weight of Methods. Infants were randomly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of >100 mL/kg/day were tolerated (EI) or at 61 days of life (late enteral iron supplementation [LI]). Nutritional iron status was assessed: 1) at birth, 2) at 61 days of life, 3) when the infants reached a weight of 1.6 times birth weight, and 4) before blood was transfused at a hematocrit of 50% one week after the onset of enteral iron supplementation. Restrictive red cell transfusion guidelines were followed and all transfusions were documented. Erythropoietin was not administered. The primary outcome variables were: 1) ferritin at 61 days and 2) the number of infants with ID. Results. Ferritin at 61 days was not different between the groups. Infants in the LI group were more often iron-deficient (26/65 vs 10/68) and received more blood transfusions after day 14 of life. No adverse effects of EI were noted. Conclusions. EI is feasible and probably safe in infants with birth weight

The aim of this study was to investigate an inflammatory response indicated by fibrinogen and plasma viscosity in relation to haemodynamic and clinical findings of patients with stable CHF due to coronary heart disease (CHD).

BACKGROUND. Iron deficiency in early childhood may impair neurodevelopment. In a masked, randomized, controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of OBJECTIVE. We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants.METHODS. Children who participated in the above mentioned trial were evaluated by applying the Kaufmann Assessment Battery for Children and the Gross Motor Function Classification Scale at the age of school entry.RESULTS. Of the 204 infants initially randomized, 10 died and 30 were lost to follow-up. A total of 164 (85% of the survivors) were evaluated at a median corrected age of 5.3 years. In this population (n = 164), the mean (±SD) mental processing composite in the early iron group was 92 (±17) versus 89 (±16) in the late iron group. An abnormal neurologic examination was found in 17 of 90 versus 26 of 74, and a Gross Motor Function Classification Scale score of >1 was found in 2 of 90 versus 5 of 74, respectively. Fifty-nine of 90 children in the early iron group were without disability, compared with 40 of 74 in the late iron group. Severe disability was found in 5 of 90 versus 6 of 74 children and 67 of 90 versus 49 of 74 qualified for regular schooling, respectively.CONCLUSIONS. Early enteral iron supplementation showed a trend toward a beneficial effect on long-term neurocognitive and psychomotor development and showed no evidence for any adverse effect. Because the initial study was not designed to evaluate effects on neurocognitive development, the power was insufficient to detect small but potentially clinically relevant improvements. Additional studies are required to confirm the trend towards a better outcome observed in the early iron group.

To determine the long-term neurodevelopmental outcome in extremely preterm infants after offering life support to all infantsor = 23 weeks gestation ("pro-active management").With parental consent, all infants born at 23 to 25 completed weeks gestation were treated proactively. Surviving infants born from July 1996 to June 1999 were assessed for standardized cognitive and neurological outcomes at 5 years corrected age.70 of 91 infants admitted to the neonatal intensive care unit survived until follow-up. 67 of the 70 surviving infants were examined at a median corrected age of 5.6 years; 12% had cerebral palsy and a Gross Motor Function Classification Scale score2; 4% were blind; 1% required a hearing aid; and 12% had a Kaufmann Assessment Battery for Children mental processing composite51, resulting in 18% sustaining a severe disability. 43% had normal results on a neurological examination, Gross Motor Function Classification Scale score = 0, mental processing composite85, and had neither severe visual nor hearing impairment. 57% qualified for regular schooling.Improved survival was not associated with an increased risk of severe disability when compared with results of earlier publications. These findings may result from proactive management and are important for counseling patients at risk of imminent extremely preterm delivery.

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated...