Esophageal perforation in attempted ERCP]

In this report we refer to a 88-years old female patient who was admitted to our hospital under the diagnosis of cholecysto- and choledocholithiasis. Due to clinical symptoms, general performance status and sonographically proven dilated bile ducts emergency-ERCP was performed by an experienced endoscopist. Unfortunately esophageal perforation occurred due to subsequently diagnosed hiatus hernia. Potential pitfalls during examination as well as a concept of problem management during endoscopies with side-view optics will be discussed.     

Prevalence of hepatitis B virus DNA in anti-HBc-positive/HBsAg-negative sera correlates with HCV but not HIV serostatus.

BACKGROUND: Hepatitis B virus (HBV) DNA often remains detectable in serum despite clinical recovery and loss of HBsAg. OBJECTIVE: To study whether coinfection with HIV and HCV influence the chance of detecting HBV DNA in sera with markers of past hepatitis B. STUDY DESIGN AND RESULTS: The test panel included 160 anti-HBc-positive/HBsAg-negative sera collected in the diagnostic setting. The following parameters were determined in the sera: anti-HIV (32% positive), anti-HCV (34% positive), HCV RNA (18% positive), and anti-HBs (37% positive). A highly sensitive PCR (90%-detection limit 100 copies/ml) amplifying the terminal protein (TP) region of HBV was established and HBV DNA was detected in 12.5% of the samples. In 70% of these samples, the HBV DNA concentration was below 500 copies/ml as measured by real-time PCR in the S gene. Logistic regression analysis revealed that the chance of detecting HBV DNA was increased by a positive HCV serostatus (odds ratio 5.0, 95%-CI 1.6-15.7), whereas HIV coinfection (odds ratio 2.0, 95%-CI 0.7-5.8), anti-HBs (odds ratio 0.9, 95%-CI 0.3-2.6), and HCV RNA status (odds ratio 0.4, 95%-CI 0.1-1.7) had no statistically significant influence. In contrast, the chance of detecting HCV RNA in the subgroup of anti-HCV-positive sera was increased by HIV coinfection (odds ratio 4.5, 95%-CI 1.2-17.4). Sequencing of the TP PCR products revealed neither a specific phylogenetic origin of the circulating HBV DNA nor clustering of uncommon mutations in the TP region. CONCLUSIONS: The prevalence of HBV DNA in serum of anti-HBc-positive/HBsAg-negative subjects correlates with HCV rather than HIV serostatus.     

200. ERCP aus chirurgischer Sicht

ZusammenfaBung Von 1968-1976 traten nach 1824 medianen Sternotomien wegen offener Herzoperationen 46 (2,5 %) Sternumdehiszenzen auf (instabiles Sternum mit oder ohne positiver Erregernachweis). Die Behandlung bestand unabhängig vom bakteriologischen Befund (28 Sternum-Infektionen, 18 blande Dehiszenzen) in frühzeitiger Wundrevision, Installation einer Spüldrainage und erneutem Sternum- und WundverschluB. Zehn Patienten verstarben an septischen Komplikationen. Gegenüber der anfangs geübten offenen Behandlung war die Überlebensrate höher sowie die Krankenhausliegezeit kürzer.     

In-vitro-Analytik und tierexperimentelle Untersuchung oberflächenmodifizierter biodegradierbarer Polylactidureterstents

With the objective of developing a biodegradable ureteric stent, various polylactides were analyzed and grafted with a clinically adapted surface. Stent moulding was performed by CESP technology (Controlled Expansion of Saturated Polymers), which is not based on high temperature but gas-loading under high pressure which induces a foamy bulk structure. The hydrolytically biodegradable, synthetic homo- and copolymers poly(D,L-lactide) (PDLLA), poly(D,L-lactide-co-trimethylene-carbonate) (PDLLA-co-TMC), poly(D,L-lactide-co-glycolide) (PDLLA-co-Gly) as derivatives of lactic acid or glycolic acid and surface modifications with hydroxyethylene-methacrylate (HEMA) and oligoethyleneoxidemonomethacrylate (OEOMA) were analyzed with regard to cytotoxicity and cell adhesion. Methacrylates have minimized protein and cell adhesion and degradation of non-toxic products. All polymers exhibited a high degree of biocompatibility and cell adhesion was markedly reduced following HEMA grafting. A 3 cm and 7 Charrière prototype of the stent was moulded from PDLLA-co-TMC by CESP-technology, and grafted with HEMA by means of plasma-induced polymerization. Finally, the stents were implanted into female sheep, following unilateral ureterotomy. Regular blood and urine analysis as well as ultrasound and the final autopsy revealed no pathological findings. Histopathological analysis exhibited a regular epithelium without any changes being determined by contact to the stent, and a good regeneration of all layers in the area of anastomosis.     

Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.

PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.     

Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.

PURPOSE: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety. RESULTS: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. CONCLUSION: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.     

Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.

BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.     

Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials.

PURPOSE: Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib. PATIENTS AND METHODS: We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC. RESULTS: EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of NSCLC. In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P = .001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype. CONCLUSION: EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers.     

Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat

Summary This report is concerned with therapeutic studies utilizing new bisphosphonic acids on tumor-induced osteolytic metastases. The bone metastases on SD rats were induced by intraarterial and intraosseous transplantation of Walker carcinosarcoma 256B ascites cells. The treatment was carried out using disodium-3-amino-1-hydroxypropylidene-1,1-bisphophonate (APD), diglycidyl-[3-(3,3-bisphosphono-3-hydroxy-propylamino)-2-hydroxypropyl-]urazol-Na₂ (DDU) and 1,2,4-triglycidylurazol (TGU). The extent of bone metastases was determined by X-ray on the 5th and 10th days following tumor inoculation, as well as both microradiographically and histologically upon termination of the experiment.High dose DDU produced a clear reduction of the tumor osteolysis, but these positive results were surpassed using APD. The best results were achieved by pretreatment with APD 24 h prior to tumor inoculation.Dedicated to Professor Dietrich Schmähl on the occasion of his 60th birthday     

Endoscopic and surgical therapy of malignant colorectal polyps

87 malignant colorectal polyps were removed in 81 patients by endoscopic polypectomy from 1972 until 1987. Thereafter 34 of these patients had a surgical resection of the colon. Surgical resection was performed for incomplete excision of the polyp (20 x), for tumor invasion of the lymphics in the polyp stalk and for moderately/poor differentiated carcinoma. In 6 patients a residual carcinoma was detected in the removed colon specimen, but lymph-node metastasis only in one with moderate-differentiated carcinoma. Our results demonstrate that colorectal polyps with invasive well-differentiated carcinoma and tumor free base do not need a surgical resection. Patients of the high-risk-group (moderately/poor-differentiated carcinoma, invasion of blood vessels and lymphatics, incomplete excision), should be referred to further surgical resection. With regard to the low rate of metastatic spread even in patients with high-risk-polyps accurate differentiation seems to be necessary. In 19 out of 52 (36.5%) patients endoscopic control examinations after surgical or endoscopic resection revealed recurrent pathological findings. On the base of the presented data we conclude that there is a need for short-term endoscopic controls over a period of five years.