Abstract: Significant progress has been made over recent years in understanding the molecular and cellular processes involved in cancer biology. The identification of several molecular targets which are involved in cancer development and progression has led to the development of novel, rationally designed, molecularly targeted agents which are currently being used or investigated in clinical practice. The different toxicity profiles, responses on imaging, and mechanisms of action of these targeted agents have implications for the way that clinical trials with these agents are conducted. This article reviews current molecularly targeted anticancer therapeutics, their future prospects, and the challenges they provide.

Abstract: BACKGROUND: The primary objectives of phase-I trials include the definition of drug toxicities and the recommendation of phase-II doses. In order to safeguard the well-being of its participants, a common inclusion criterion is that of life expectancy >3 months. However, previous studies have shown that about 20% of these patients do not survive beyond this time-point. METHODS: We identified 97 patients who died within the first 90 days of treatment out of a total of 654 consecutively treated phase-I patients, from June 2003 to June 2007. This cohort was compared to a control group comprising 215 patients who lived >90 days on phase-I studies and were treated from January 2005 to June 2006. RESULTS: In keeping with our recently reported phase-I survival risk score, multivariate analysis demonstrated that patients who died within the first 90 days had lower albumin (p=0.010), greater number of metastatic sites (p=0.00001) and higher frequency of elevated LDH (p=0.0002). This analysis also showed that 86% of patients who died during the first 90 days had an increased risk score of 2/3 compared to 39% in the control group. Furthermore, three additional factors were identified, namely younger age (p=0.024), higher white cell count (p=0.028) and poorer ECOG PS (p=0.012) but the addition of these did not improve the ability to predict 90-day mortality compared to the afore-mentioned risk score. CONCLUSIONS: There is good evidence that our easily derivable scoring system provides an objective method to identify patients with a very limited life expectancy in whom participation in phase-I trials should be carefully evaluated.

Abstract: Abstract: BACKGROUND AND AIMS: Microsatellite instability (MSI) is a potential indicator of prognosis in patients with colorectal cancer (CRC). To date, there are a limited number of studies which investigated its role in advanced CRC. Our study investigated the value of high degree of MSI (MSI-H) in patients treated with 5-FU/oxaliplatin-based chemotherapy which has been done by only one further study recently. PATIENTS AND METHODS: In this study, we investigated tumour tissues from 108 patients with metastatic CRC who were treated in a prospective, randomised trial comparing two oxaliplatin and 5-FU-based therapy regimens (FUFOX vs. CAPOX) involving a total of 474 patients. We determined the incidence and prognostic value of a high degree of microsatellite instability. The specimens were analysed by PCR corresponding to the National Institute of Health reference panel. In addition, immunostaining of the mismatch repair proteins MLH1, MSH2 and MSH6 was performed. RESULTS AND FINDINGS: The incidence of MSI-H was 4%. MSI-H was correlated with a lower rate of disease control compared to non-MSI-H patients (p = 0.02). However, there was no correlation between MSI-H and progression-free survival or overall survival. INTERPRETATION AND CONCLUSION: MSI-H incidence in metastatic CRC was low. Our data suggest that MSI-H may be correlated with a poorer response to a 5-FU/oxaliplatin treatment. This finding needs confirmation in a larger cohort.

Abstract: BACKGROUND: The purpose of this study was to evaluate the association of circulating tumour cell (CTC) counts, before and after commencing treatment, with overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). Experimental design: A 7.5 ml of blood was collected before and after treatment in 119 patients with CRPC. CTCs were enumerated using the CellSearch(R)System. RESULTS: Higher CTC counts associated with baseline characteristics portending aggressive disease. Multivariate analyses indicated that a CTC >/=5 was an independent prognostic factor at all time points evaluated. Patients with baseline CTC >/=5 had shorter OS than those with <5 [median OS 19.5 versus >30 months, hazard ratio (HR) 3.25, P = 0.012]; patients with CTC >50 had a poorer OS than those with CTCs 5-50 (median OS 6.3 versus 21.1 months, HR 4.1, P < 0.001). Patients whose CTC counts reduced from >/=5 at baseline to <5 following treatment had a better OS compared with those who did not. CTC counts showed a similar, but earlier and independent, ability to time to disease progression to predict OS. CONCLUSION: CTC counts predict OS and provide independent prognostic information to time to disease progression; CTC dynamics following therapy need to be evaluated as an intermediate end point of outcome in randomised phase III trials.

Abstract: AIM: To identify factors that may prevent or delay patients referred for consideration of phase I studies from commencing such a study. METHODS: A retrospective audit of phase I study referrals for the period 1st March to 31st August 2005 to the Drug Development Unit was performed. All reasons that led to either delay or recruitment failure were documented and analysed. RESULTS: Data from 176 patients (105M/71F) were analysed. Median age at referral was 59 years and median performance status (PS) was 1. Of these, 56 (32%) were successfully recruited in a phase I trial. The median time from trial allocation to commencement of treatment was 4.8 weeks. Poor or deteriorating PS was the reason for delay or recruitment failure in 43 (35%) of non-recruited patients. CONCLUSIONS: Poor or deteriorating PS was the most common factor limiting accrual to phase I trials. Better patients' selection on this basis might improve recruitment rates.

Abstract: BACKGROUND: We evaluated the outcome of 140 patients aged > or = 70 years of age who received first-line treatment for metastatic colorectal cancer within the German phase III trial of FUFOX (5-fluorouracil/leucovorin/oxaliplatin) versus CAPOX (capecitabine/oxaliplatin). PATIENTS AND METHODS: One hundred forty (30%) elderly patients of 476 total patients were identified, and 138 patients received the CAPOX or FUFOX treatment. RESULTS: Overall, treatment was well tolerated, and grade 3/4 toxicities were similar in both groups, with more gastrointestinal side effects in the elderly group but less neurosensory side effects. The response rate (RR) was comparable between both cohorts (49% in elderly patients vs. 52% in patients aged < 70 years). Median progression-free survival (PFS) was 7.7 months for patients aged > or = 70 years and 7.5 months for patients aged < 70 years (hazard ratio [HR], 1.07; 95% CI, 0.86-1.34). With regard to the chemotherapy regimen, there was no inferiority between FUFOX and CAPOX in patients aged > or = 70 years (7.9 months vs. 7.6 months). The median overall survival (OS) between FUFOX and CAPOX was comparable in patients aged > or = 70 years (14.4 months vs. 14.2 months). However, when compared with patients aged < 70 years, the median OS was significantly shorter (18.8 months vs. 14.4 months; P = 0.013; HR, 1.37; 95% CI, 1.07-1.76). This was consistent with our multivariate analysis, which revealed that age > or = 70 years was a negative factor for OS. CONCLUSION: Oxaliplatin combined with 5-FU/leucovorin or capecitabine was generally well tolerated in elderly patients. Elderly patients had similar PFS and overall RRs compared with the population aged < 70 years, but the OS was shorter.

Abstract: Background: The purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT). Patients and methods: Data on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4-27.3). Demography at ASCT was 61% stage IV, median age 31 years (18-69), median prior treatment (tx) regimens 3 (2-7), median Hasenclever index 3 (0-6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease. Results: Post-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years. Conclusion: These data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.

Abstract: The main aim of phase I trials is to evaluate the tolerability and pharmacology of a new compound. However, investigating the potential for clinical benefit is also a key objective. Our phase I trial portfolio incorporates a range of new drugs, including molecular targeted agents, sometimes given together with cytotoxic agents. We performed this analysis of response rate, progression-free (PFS) and overall survival (OS) to assess the extent of clinical benefit rate (CBR: partial response (PR)+stable disease (SD)) derived from current trials. We analysed 212 consecutive patients who were treated in 29 phase I studies, from January 2005 to June 2006. All patients had progression of disease prior to study entry. The median age was 58 years (range: 18-86) with a male/female ratio of 2 : 1. A total of 148 patients (70%) were treated in 'first in human trials' involving biological agents (132 patients) or new cytotoxic compounds (16 patients) alone, and 64 patients (30%) received chemotherapy-based regimens with or without biological agents. After a median follow-up time of 34 weeks, the median PFS and OS were 11 and 43 weeks, respectively. The CBR was 53% (9% PR and 44% SD) after the first tumour evaluation after two cycles (between weeks 6 and 8) and has been maintained at 36 and 26% at 3 and 6 months, respectively. Treatment related deaths occurred in 0.47% of our patients and treatment had to be withdrawn in 11.8% of patients due to toxicity. A multivariate analysis (MVA) of 13 factors indicated that low albumin (<35 g l(-1)), lactate dehydrogenase>upper normal limit and >2 sites of metastasis were independent negative prognostic factors for OS. A risk score based on the MVA revealed that patients with a score of 2-3 had a significantly shorter OS compared to patients with a score of 0-1 (24.9 weeks, 95% CI 19.5-30.2 vs 74.1 weeks, 95% CI 53.2-96.2). This analysis shows that a significant number of patients who develop disease progression while receiving standard therapy derived benefit from participation in phase I trials. Risk scoring based on objective clinical parameters indicated that patients with a high score had a significantly shorter OS, and this may help in the process of patient selection for phase I trial entry.British Journal of Cancer (2008) 98, 1029-1033. doi:10.1038/sj.bjc.6604218 www.bjcancer.com Published online 18 March 2008.

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Abstract: PURPOSE: Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX. PATIENTS AND METHODS: This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity. RESULTS: The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia-HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens. CONCLUSION: The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.

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Abstract: BACKGROUND: Relapse in the central nervous system (CNS) following initial treatment of diffuse large B-cell lymphoma (DLBCL) is an uncommon but serious complication. This single centre retrospective study investigated the rate of CNS relapse in patients with DLBCL who received standardised intrathecal (IT) chemoprophylaxis. PATIENTS AND METHODS: A total of 259 patients were newly diagnosed and treated for DLBCL from October 1996 to May 2005 and retrospectively analysed for incidence of CNS relapse. Our institutional policy for patients at risk for CNS relapse was for IT chemoprophylaxis to be administered concurrently with systemic treatment. Defined at-risk patients were those with lymphoma involvement at the following sites: bone marrow, testis, nasal/paranasal sinuses, orbits, bone/vertebrae and peripheral blood. RESULTS: Of 259 patients with DLBCL, a total of 51 patients (19.7%) received IT chemoprophylaxis. Forty-four patients received single agent IT methotrexate (MTX) 12.5 mg (median 3 doses, range 1-7); 27 patients (53%) received 1-3 doses and 17 patients (33.3%) 4-7 doses of MTX. Seven patients (13.7%) received a combination of IT MTX plus cytarabine. Three patients (1.1%) subsequently developed CNS relapse. One of these patients had IT chemoprophylaxis, the other two did not meet the Royal Marsden Hospital (RMH) criteria for IT chemoprophylaxis. The median time from diagnosis of DLBCL to CNS relapse was 31.8 months (range 27.3-34.1 months). CONCLUSION: The CNS relapse rate in this cohort of patients with primary DLBCL was low at 1.1%. This retrospective analysis demonstrates in a homogeneous group of DLBCL patients that a relatively low-intensity IT chemoprophylaxis regimen given according to site-based risk can be associated with a low risk of CNS relapse.

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Abstract: PURPOSE: To compare the use of capecitabine plus oxaliplatin (CAPOX) with infusional fluorouracil (FU)/folinic acid plus oxaliplatin (FUFOX) as first-line therapy for patients with metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: A total of 474 patients with MCRC received either CAPOX (capecitabine 1,000 mg/m2 bid, days 1 to 14 plus oxaliplatin 70 mg/m2 days 1 and 8, repeated every 22 days) ) or FUFOX (oxaliplatin 50 mg/m2 followed by leucovorin 500 mg/m2 plus FU 2,000 mg/m2 as a 22-hour infusion days 1, 8, 15, and 22, repeated every 36 days). The primary end point was progression-free survival (PFS). Secondary end points were response rate (RR), overall survival (OS), time to treatment failure, and toxicity. The study was designed to determine noninferiority for the CAPOX regimen. RESULTS: Median PFS was 7.1 months in the CAPOX arm and 8.0 months in the FUFOX arm (hazard ratio [HR], 1.17; 95% CI, 0.96 to 1.43; P = .117). Median OS was 16.8 months (CAPOX) and 18.8 months (FUFOX; HR, 1.12; 95% CI, 0.92 to 1.38; P = .26). Overall RRs were 48% for CAPOX (95% CI, 41% to 54%) and 54% for FUFOX (95% CI, 47% to 60%). Both regimens were generally well tolerated, although there was a significantly higher incidence of grade 2/3 hand-foot syndrome (HFS) in the CAPOX arm (P = .028). CONCLUSION: CAPOX resulted in a slightly inferior efficacy than FUFOX. With respect to PFS, the best estimate of the HR of 1.17 was within the prespecified equivalence range. However, a relevant inferiority cannot be excluded. Both regimens were generally well tolerated but there was a significantly higher rate of grade 2/3 HFS in the CAPOX arm.

Abstract: Colorectal cancer (CRC) is one of the most common cancers in the Western world, with > 500,000 new cases diagnosed each year. One of the strongest risk factors for colon cancer is age. The incidence rates rise from 10 in 100,000 at age 40-45 years to 300 in 100,000 at age 75-80 years, with the median age at diagnosis of CRC being 71 years. With the general demographic shift toward an aging population, the number of people aged > 65 years is expected to increase. This article reviews the development of treatment for elderly patients with metastatic CRC, from single-agent fluoropyrimidines to combination therapies.

Abstract: We evaluated the expression patterns of proapoptotic BAX, antiapoptotic Bcl-2 and p53, the proposed upstream effector of these molecules, as potential prognostic markers in UICC stage III colon cancer by immunohistochemical staining. To identify high-frequency microsatellite instability (MSI+) individuals, we performed single-strand conformation polymorphism-based analysis for BAT26. A total of 188 patients who had received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (5-FU/folinic acid or 5-FU/levamisole) were enrolled. Median follow-up was 84.5 months. We found that BAX, Bcl-2 and p53 protein expressions were high or positive in 59, 70 and 50% of 188 cases, respectively. MSI+ tumours were detected in 9% of 174 evaluable patients. BAX or Bcl-2 was correlated with a higher degree of differentiation or left-sided tumours (P=0.01 or P=0.03, respectively); MSI was correlated with right-sided tumours (P<0.0001). In contrast to p53, Bcl-2, or MSI, low BAX, advanced pN category, low grade of differentiation and treatment with 5-FU/levamisole were univariately associated with poorer disease-free survival (DFS) (P=0.0005, P=0.001, P=0.005 and P=0.01, respectively) and poorer overall survival (OS) (P=0.002, P=0.0001, P=0.003 and P=0.02, respectively). Besides pN category and treatment arm, BAX was an independent variable related to both OS and DFS (P=0.003 and P=0.001, respectively). In both univariate and multivariate analysis, the p53-/BAX high in comparison with the p53+/BAX high subset conferred a significantly improved DFS (P=0.03 and P=0.03, respectively) as well as a marginally improved OS (P=0.07 and P=0.08, respectively). BAX protein expression may be of central significance for clinical outcome to 5-FU-based adjuvant chemotherapy in stage III colon cancer, and bivariate analysis of p53/BAX possibly may provide further prognostic evidence.

Abstract: Mucosa associated lymphoid tissue (MALT) lymphoma of the lung is a rare disease with an indolent clinical behaviour. This single centre retrospective analysis evaluates the treatment strategies and clinical outcome for these patients. A total number of ten patients (7 male/3 female) were identified between January 1997 and October 2005 and their records analysed. At diagnosis the patients presented with unspecific symptoms (cough, shortness of breath and lower respiratory chest infection) which were further evaluated. Six patients had stage IAE disease, two patients stage IIAE and in two patients disease was stage IV. The initial treatment consisted of surgery alone (3 patients), chemotherapy +/- rituximab (5/1 patients), single agent rituximab (1 patient) and wait & watch strategy (1 patient). After a median follow-up time of 3.4 years the overall survival was 90% at 3 years. In conclusion, our data suggest that most of the patients with MALT of the lung had localized disease which generally responded well to systemic or local therapy and resulted in favourable long-term outcome underlining the indolent course of this disease.

Abstract: Novel, effective therapies are needed for peripheral T-cell non-Hodgkin's lymphoma (PTCL). We treated 16 patients with a combination of gemcitabine, cisplatin and methylprednisolone (GEM-P). Three patients (19%) achieved a complete remission and eight (50%) a partial remission. GEM-P has encouraging efficacy with an acceptable toxicity profile in patients with PTCL.

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Abstract: Der Gebrauch von Capecitabin, einem oralen Fluoropyrimidin, hat in den letzten Jahren stetig zugenommen, da seine Wirkung vergleichbar mit infusionalem 5-Fluorouracil ist und Studien gezeigt haben, dass das Toxizitätsprofil vergleichbar geringer ausfällt. Capecitabin wird als Monosubstanz, aber auch in Kombination mit anderen Chemotherapeutika, wie z.B. Oxaliplatin, Irinotecan oder Docetaxel verabreicht und ist für die Behandlung einer Reihe von Tumorentitäten zugelassen. Eine typische Nebenwirkung durch die Behandlung mit Fluoropyrimidinen, aber auch anderen Chemotherapeutika, wie z.B. Doxorubicin, Vinorelbin und Docetaxel ist das so genannte Hand-Fuss-Syndrom (HFS), oder die palmar-plantare Erythrodysästhesie. Das HFS erscheint als eine erythematöse Hautveränderung der Handinnenflächen und Fußsohlen und wird klinisch in drei verschiedene Stadien eingeteilt, das vom schmerzlosen Erythem ohne Beeinträchtigung des täglichen Lebens (Grad1) bis hin zur schmerzhaften ulzerativen Dermatitis, die zu Funktionseinschränkungen (Grad 3), führen kann.

Abstract: BACKGROUND: Adjuvant postoperative treatment with 5-fluorouracil (5-FU) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. The impact of continuous 5-FU with and without leucovorin on survival and tumor recurrence was analyzed in this study compared with the effects of bolus 5-FU/leucovorin. PATIENTS AND METHODS: Patients with a curatively resected UICC stage III colon cancer were stratified according to T, N and G category and randomly assigned to receive one of the three adjuvant treatment schemes: 5-FU 450 mg/m2 and leucovorin 100 mg/m2 x 5 days every 4 weeks; six cycles, arm A; 24-h infusion of high-dose 5-FU/leucovorin 2,600 mg/m2 and 500 mg/m2, two cycles of six applications, arm B; 24-h infusion of high-dose 5-FU 2,600 mg/m2, two cycles of six applications, arm C. RESULTS: One hundred and forty-five patients enrolled into this study were eligible. To date, 28 patients have died; 9 on arm A, 11 on arm B, and 8 on arm C (P was nonsignificant). After a median follow-up time of 45 months, there was no statistical difference in survival and tumor recurrence between the three treatment arms. Adjuvant treatment in all arms was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSION: There is no statistical difference in efficacy and toxicity in patients receiving either high-dose 5-FU with or without leucovorin or the standard 5-FU bolus regime after a curative resection of a stage III colon cancer.

Abstract: We report on two spontaneous cases of microangiopathic hemolytic anemia (MAHA) as first manifestation due to metastasized signet ring carcinoma, one of gastric and one of unknown origin. The patients presented with an acute onset of Coombs negative hemolytic anemia and fragmentocytes in the peripheral blood smear which are typical for MAHA. These case reports present MAHA as a rare paraneoplastic syndrome in patients with metastasized signet ring carcinoma. Parallel to symptomatic treatment we started chemotherapy treatment (ELF and PLF regimen, respectively). In both cases we were able to control the MAHA and cancer progression.

Abstract: Studien haben gezeigt, daß eine zusätzliche adjuvante Chemotherapie die Rezidivrate bei Patienten mit kurativ reseziertem Kolonkarzinom im Stadium III signifikant verringern kann. Anfang der 90er wurde aufgrund von Studienergebnissen die Kombination einer zwölfmonatigen 5-Fluorouracil/Levamisol-Therapie propagiert. Diese Therapie wurde im Verlauf durch eine 5-Fluorouracil/ Leucovorin-Kombination abgelöst. Bis zum heutigen Zeitpunkt ist die Frage, ob Patienten im Stadium II von dieser Kombination profitieren, nicht geklärt. Durch neue Medikamente, wie z.B. Irinotecan oder Oxaliplatin, soll die Wirksamkeit von 5-Fluorouracil/Leucovorin weiter verbessert werden. Erste Ergebnisse einer Kombinationsstudie aus Hochdosis-5-Fluorouracil/Leucovorin + Oxaliplatin liegen bereits vor und zeigen zum jetzigen Zeitpunkt eine geringere Rezidivrate gegenüber der Kombination 5-Fluorouracil/Leucovorin. Zum jetzigen Zeitpunkt kann noch keine Aussage gemacht werden, ob das orale 5-FU-Prodrug, Capecitabin, alleine oder in Kombination mit Oxaliplatin in der adjuvanten Therapie die Standardregime ablösen kann.

Abstract: We report on a 35-year old women with severe abdominal pain, cramps, diarrhea with blood and a palpable paraumbilical resistance. The symptoms appeared a few days before admission and were recurrent within the last two years. The abdominal ultrasound showed a target sign with a thickened wall from the right to the left colon flexure with inhomogeneous reflexes. The CT-scan and barium enema showed an intussusception of the colon. After hemicolectomy of the right colon a 6 x 4 x 4 cm exophytic tumor near the ileocoecal valve was detected. Histologically the tumor was diagnosed as adenocarcinoma of the coecum (pT2pNOpMX G2).

Abstract: BACKGROUND: Adjuvant postoperative treatment with 5-fluorouracil (5-FU) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrences and improves survival. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in a long-term follow-up study in comparison with the effects of 5-FU plus levamisole in the prospective multicenter trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected stage III (International Union Against Cancer) colon cancer were stratified according to tumor, node and grading category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body surface area intravenously in the first chemotherapy course, then 450 mg/m2 x 5 days, plus leucovorin 100 mg/m2, 12 cycles (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred and eighty (96.9%) of 702 patients enrolled into this study were eligible. To date, 261 patients have died, 117 on arm A and 144 on arm B (P = 0.007). After a median follow-up time of 82 months, the 5-FU plus leucovorin combination significantly improved disease-free survival [79.8 months in arm A versus 69.3 months in arm B (P = 0.012)] and significantly increased median overall survival (88.9 months in arm A versus 78.6 months in arm B; P = 0.003). Adjuvant treatment with 5-FU plus levamisole as well as 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSIONS: After curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated. This long-term follow-up study demonstrates that adjuvant treatment with 5-FU plus leucovorin given for 12 cycles is significantly more effective than 5-FU plus levamisole (Moertel scheme) in reducing tumor relapse and improving survival.

Abstract: Chronic liver diseases are accompanied by changes in splanchnic and systemic circulation. These changes are characterised by a reduction in peripheral vascular resistance and an increased cardiac output at rest. An increased release of nitric oxide (NO) has been proposed to play a role in the pathogenesis of vasodilatation and vascular hypocontractility. This study was designed to determine the nitric oxide metabolism measured as circulating nitrate levels in serum/urine in patients with chronic liver disease and cirrhosis. The nitrate concentrations were significantly increased in advanced degrees in cirrhosis Child B and C, and normal or even reduced in patients with chronic active hepatitis and early cirrhosis. In our study the connections between the extent of portal hypertension and nitrate levels were evident. The presence of ascites as well as the the progression of oesophageal varices were associated with higher circulating nitrate levels. The connection between increased nitric oxide production and the haemodynamic sequelae of portal hypertension is also apparent in the significant correlation between plasma renin and serum nitrate levels. Circulating nitrate levels also correlated to the serum interleukin-6 levels. This study demonstrated that the increased nitric oxide metabolism is associated with the haemodynamic alterations induced by portal hypertension.

Abstract: We studied the activity of combined oxaliplatin and fluorouracil-leucovorin in 16 consecutive patients with advanced biliary tract adenocarcinomas. The disease control rate (responses and stable disease) was 56% (95% confidence interval, 29-84%) and the median overall survival time was 9.5 months (range 0.9-26.8+). Therefore, this regimen might be active in biliary adenocarcinomas with further evaluation necessary.

Abstract: CLINICAL SYMPTOMS: We report of a 52-year-old man from Egypt who suffered from 20 kg weight loss within 6 months, jaundice, macrohematuria, and impaired renal function. INVESTIGATIONS AND THERAPY: Due to the ultrasound and the CT scan of the abdomen, a kidney tumor was suspected. A nephrectomy was planned but the biopsy of the kidney and liver intraoperatively revealed amyloid deposits. A plasma cell dyscrasia of 15% was found by bone marrow biopsy. Immunfixation showed an IgG-kappa light chain in plasma and urine. There was no osteolysis throughout the skeletal system. Thus, the patient had a plasmacytoma Stage II associated with IgG-kappa light chain AL-amyloidosis which was treated by chemotherapy (melphalan and prednisolone). CONCLUSION: This unusual case presents a cholestatic liver disease due to bile duct obstruction secondary to amyloid deposits. Although AL-amyloidosis is easily diagnosed by certain criteria, the disease is often recognized too late with consequently poor prognosis.

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