Chemotherapy for metastatic colon cancer: No effect on survival when the dose is reduced due to side effects.

BACKGROUND: 5-Fluorouracil (5FU), Folinic acid (FA), and Oxaliplatin (FOLFOX) or 5FU, FA, and Irinotecan (FOLFIRI) are standard regimens for palliative chemotherapy of metastatic colon cancer. Since data showing the influence of dose reduction in palliative treatment are rare, the objective of this single center, retrospective study was to further characterize the influence of dose reduction on efficacy of these therapeutic regimens. METHODS: One hundred nine patients, diagnosed with stage IV colon cancer between 2004 and 2012 and receiving palliative first-line chemotherapy with either FOLFOX or FOLFIRI regimens in our outpatient clinic were analyzed for treatment efficacy. Patients who received dose reductions due to side effects usually received doses of 80% or lower of per protocol dose. Survival data were obtained from the Regensburg Tumor Registry. Survival analysis was performed using Kaplan-Meier statistical analysis and multivariable analysis. RESULTS: A dose reduction due to side effects was necessary in 46 (42%) patients. Dose reduction was independent of age. Major reasons for dose reduction were neutropenia (30%) followed by polyneuropathy (16%) and diarrhea (14%). Dosage was more often reduced in patients receiving FOLFOX based therapy. Comparison of patients with dose reduction versus patients with full dosage showed no significant difference on overall survival (p = 0.430). Subgroup analysis revealed dose reduction in patients with N2 stage disease was associated with improved survival. Patients who underwent dose reduction received more cycles of chemotherapy (13.7 vs. 10.8 cycles) and cumulative dosage was similar in both groups. CONCLUSION: Contrary to our expectations, the need to reduce chemotherapy dosage due to side effects does not indicate a worse prognosis in our retrospective analysis. We believe this can in part be explained by better adaption to interindividual pharmacokinetics and longer time of treatment.

Advanced Mucinous Colorectal Cancer: Epidemiology, Prognosis and Efficacy of Chemotherapeutic Treatment.

BACKGROUND: The clinicopathological significance of the mucinous subtype of colorectal cancer (CRC) remains controversial. As of today, none of the current guidelines differentiate treatment with respect to mucinous or nonmucinous cancer. Due to the lack of substantiated data, best treatment remains unclear and the mucinous subtype of CRC is usually treated along the lines of recommendations for adenocarcinoma of the colon. METHODS: We investigated an East-Bavarian cohort of 8,758 patients with CRC. These included 613 (7.0%) patients with a mucinous subtype, who were analyzed for assessing their characteristics in clinical course and for evaluating the efficacy of common chemotherapy protocols. RESULTS AND CONCLUSION: Mucinous CRC was predominantly located in the right hemicolon; it was diagnosed at more advanced stages and occurred with preponderance in women. A higher rate of G3/4 grading was observed at diagnosis (all p < 0.001). An association of mucinous CRC with younger age at initial diagnosis, previously reported by other groups, could not be confirmed. Patients with mucinous stage IV colon cancer demonstrated poorer survival (p = 0.006). In contrast, no differences in survival were observed for specific stages I-III colon cancer. Stage-dependent analysis of rectal cancer stages I-IV also showed no differences in survival. However, univariable overall analysis resulted in significant poorer survival of mucinous compared to nonmucinous rectal cancer (p = 0.029). Also, combined analysis of all patients with mucinous CRC revealed poorer overall survival (OS) of these patients compared to nonmucinous CRC patients (median 48.4 vs. 60.2 months, p = 0.049) but not in multivariable analysis (p = 0.089). Chemotherapeutic treatment showed comparable efficacy regarding OS for mucinous and nonmucinous cancers in both an adjuvant and palliative setting for colon cancer patients (p values comparing mucinous and nonmucinous cancers < 0.001-0.005).

Significance of scintigraphy for the localisation of obscure gastrointestinal bleedings.

AIM: To determine the role of scintigraphy in patients with gastrointestinal (GI) bleeding of unknown localisation. METHODS: We performed retrospective analyses on 92 patients receiving scintigraphies from 1993 to 2000 in the University of Regensburg hospital, which were done for localisation of GI bleeding as a diagnostic step after an unsuccessful endoscopy. In addition to the scintigraphies, further diagnostic steps such as endoscopy, angiography or operations were performed. In some of the scintigraphies with negative results, a provocation test for bleeding with heparinisation was carried out. RESULTS: 73% of all scintigraphies showed a positive result. In 4.5% of the positive results, the source was located in the stomach, in 37% the source was the small bowel, in 25% the source was the right colon, in 4.5% the source was the left colon, and in 20% no clear localisation was possible. Only 4% of all scintigraphies were false positive. A reliable positive scintigraphy was independent of the age of the examined patient. A provocation test for bleeding with heparin resulted in an additional 46% of positive scintigraphies with a reliable localisation in primary negative scintigraphies. CONCLUSION: Our results show that scintigraphy and scintigraphy with heparin provocation tests are reliable procedures. They enable a reliable localisation in about half of the obscure GI-bleeding cases. Scintigraphy is superior to angiography in locating a bleeding. It is shown that even in the age of video capsule endoscopy and double-balloon enteroscopy, scintigraphy provides a reliable and directed localization of GI bleeding and offers carefully targeted guidance for other procedures.

Combined skin disinfection with chlorhexidine/propanol and aqueous povidone-iodine reduces bacterial colonisation of central venous catheters.

OBJECTIVE: Central venous catheter (CVC)-related infections may be caused by micro-organisms introduced from the skin surface into deeper tissue at the time of CVC insertion. The optimal disinfection regimen to avoid catheter-related infections has not yet been defined. This study compares three different approaches. DESIGN: Prospective randomised trial. SETTING: A tertiary care hospital. PATIENTS AND PARTICIPANTS: One hundred nineteen patients scheduled electively to receive 140 CVCs. INTERVENTIONS: Skin disinfection was performed with either povidone-iodine 10% (PVP-iodine), chlorhexidine 0.5%/propanol 70%, or chlorhexidine 0.5%/propanol 70% followed by PVP-iodine 10%. Prior to disinfection, a swab from the site of insertion was taken for culture. CVCs were removed if no longer needed or infection was suspected. All catheters were cultured quantitatively after removal. MEASUREMENT AND RESULTS: Bacteria could be isolated from 20.7% of the catheter tips. Bacterial growth was found in 30.8% of the catheters placed after skin disinfection with povidone-iodine, in 24.4% after disinfection with propanol/chlorhexidine and in 4.7% after disinfection with propanol/chlorhexidine followed by povidone-iodine ( p=0.006). In 15 cases, the same organism was isolated from the skin swab and the catheter tip. Ten of these paired isolates showed the same pattern in a pulsed-field gel electrophoresis analysis. CONCLUSIONS: Skin disinfection with propanol/chlorhexidine followed by PVP-iodine was superior in the prevention of microbial CVC colonisation compared to either of the regimens alone. These results support the concept that catheter infections can originate from bacterial translocation at the time of catheter insertion.

Secondary use of the EHR via pseudonymisation.

The Electronic Health Record (EHR) has many secondary uses, such as health economy and health care research, or disease specific clinical or epidemiological research. For these uses in general the patient identity is not needed, therefore the data must be anonymised or pseudonymised. Whereas for one-time use of the data this procedure is straightforward, long-term data accumulation or the necessity of re-identification require a more sophisticated approach. This paper describes possible model architectures, developed for medical research networks, but useful in other contexts as well.

Collection of annotated data in a clinical validation study for alarm algorithms in intensive care--a methodologic framework.

INTRODUCTION: Monitoring of physiologic parameters in critically ill patients is currently performed by threshold alarm systems with high sensitivity but low specificity. As a consequence, a multitude of alarms are generated, leading to an impaired clinical value of these alarms due to reduced alertness of the intensive care unit (ICU) staff. To evaluate a new alarm procedure, we currently generate a database of physiologic data and clinical alarm annotations. METHODS: Data collection is taking place at a 12-bed medical ICU. Patients with monitoring of at least heart rate, invasive arterial blood pressure, and oxygen saturation are included in the study. Numerical physiologic data at 1-second intervals, monitor alarms, and alarm settings are extracted from the surveillance network. Bedside video recordings are performed with network surveillance cameras. RESULTS: Based on the extracted data and the video recordings, alarms are clinically annotated by an experienced physician. The alarms are categorized according to their technical validity and clinical relevance by a taxonomy system that can be broadly applicable. Preliminary results showed that only 17% of the alarms were classified as relevant, and 44% were technically false. DISCUSSION: The presented system for collecting real-time bedside monitoring data in conjunction with video-assisted annotations of clinically relevant events is the first allowing the assessment of 24-hour periods and reduces the bias usually created by bedside observers in comparable studies. It constitutes the basis for the development and evaluation of "smart" alarm algorithms, which may help to reduce the number of alarms at the ICU, thereby improving patient safety.

[Quality management: implementation of the "in-hospital" emergency protocol into clinical routine]. / Qualitätsmanagement: Implementierung des "In-Hospital"-Notfallprotokolls in die klinische Praxis.

BACKGROUND AND PURPOSE: Outcome after in-hospital resuscitation with survival rates between 14-17% still remains poor. Structured documentation of in-hospital cardiac arrest especially in Germany is rare and inhomogeneous. Documentation of in-hospital emergency situations (I-ES) may help to develop organizational structures, to collect information of treatment after resuscitation and therefore, improve patient's outcome. The aim of this study was to evaluate the documentation quality and user's acceptance after the implementation of an in-house emergency (IHE) protocol used by the authors' internal medicine emergency team (ET). METHODS: Analysis of IHE protocols and discharge letters of 65 patients between August 2004 and December 2007 at a university medical center. RESULTS: The IHE protocol was used in 65% of all emergency calls with a completion rate of 80% of all available documentation categories. Especially documentation of drugs given, their dosage and the general course of action was incomplete. In 25% the discharge letters did not contain information about the I-ES. CONCLUSION: Implementation of the authors' IHE protocol, designed in close accordance with the DIVI (German Interdisciplinary Association of Intensive Care and Emergency Medicine) out-of-hospital emergency protocol, helps to collect important data in I-ES. Usage of the protocol resulted in better documentation of emergency situations in contrast to the information found in discharge letters alone. Nevertheless, documentation of I-ES still needs to be improved, especially concerning the completeness of records.