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Background: An isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects in comparison with systemic palliative chemotherapy. The aim of the present study was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop flow technique with commercially available tools in patients with advanced pancreatic carcinoma. Methods: Seventeen patients with unresectable or metastasized pancreatic carcinoma (diagnosed by histological investigation) underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 mitomycin C (MitomedacTM, medac, Hamburg, Germany) 22 times. Cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. Results: The mitomycin C concentration was 10 times higher within the regional compared with the systemic compartment at its maximum. The area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission, 2 partial remissions). In 3 subjects, stable disease was registered, and in 11 individuals, tumor progression. The median survival was 4.1 months. Conclusion: Though high concentrations of the cytostatic drug were achieved within the regional compartment, the aortic stop flow technique was associated with a high toxicity rate but no improvement of tumor response and survival in comparison with systemic chemotherapy. Despite its pharmacokinetic advantages, the aortic stop flow technique is currently not recommendable for routine use.Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: In the surgical treatment of colorectal carcinoma (CRC), 1 in 10 patients has a peritumorous adhesion or tumor infiltration in the adjacent tissue or organs. Accordingly, multivisceral resection (MVR) must be performed in these patients. This prospective multicenter observational study aimed to analyze the possible differences between non-multivisceral resection (nMVR) and MVR in terms of early postoperative and long-term oncological treatment outcomes. We also aimed to determine the factors influencing overall survival., Methods: The data of 25,321 patients from 364 hospitals who had undergone surgery for CRC (the Union for International Cancer Control stages I-III) during a defined period were evaluated. MVR was defined as (partial) resection of the tumor-bearing organ along with resection of the adherent and adjacent organs or tissues. In addition to the patients' personal, diagnosis (tumor findings), and therapy data, demographic data were also recorded and the early postoperative outcome was determined. Furthermore, the long-term survival of each patient was investigated, and a "matched-pair" analysis was performed., Results: From 2008 to 2015, the MVR rates were 9.9 % (n=1,551) for colon cancer (colon CA) and 10.6 % (n=1,027) for rectal cancer (rectal CA). CRC was more common in men (colon CA: 53.4 %; rectal CA: 62.0 %) than in women; all MVR groups had high proportions of women (53.6 % vs. 55.2 %; pairs of values in previously mentioned order). Resection of another organ frequently occurred (75.6 % vs. 63.7 %). The MVR group had a high prevalence of intraoperative (5.8 %; 12.1 %) and postoperative surgical complications (30.8 % vs. 36.4 %; each p<0.001). Wound infections (colon CA: 7.1 %) and anastomotic insufficiencies (rectal CA: 8.3 %) frequently occurred after MVR. The morbidity rates of the MVR groups were also determined (43.7 % vs. 47.2 %). The hospital mortality rates were 4.9 % in the colon CA-related MVR group and 3.8 % in the rectal CA-related MVR group and were significantly increased compared with those of the nMVR group (both p<0.001). Results of the matched-pair analysis showed that the morbidity rates in both MVR groups (colon CA: 42.9 % vs. 34.3 %; rectal CA: 46.3 % vs. 37.2 %; each p<0.001) were significantly increased. The hospital lethality rate tended to increase in the colon CA-related MVR group (4.8 % vs. 3.7 %; p=0.084), while it significantly increased in the rectal CA-related MVR group (3.4 % vs. 3.0 %; p=0.005). Moreover, the 5-year (yr) overall survival rates were 53.9 % (nMVR: 69.5 %; p<0.001) in the colon CA group and 56.8 % (nMVR: 69.4 %; p<0.001) in the rectal CA group. Comparison of individual T stages (MVR vs. nMVR) showed no significant differences in the survival outcomes (p<0.05); however, according to the matched-pair analysis, a significant difference was observed in the survival outcomes of those with pT4 colon CA (40.6 % vs. 50.2 %; p=0.017). By contrast, the local recurrence rates after MVR were not significantly different (7.0 % vs. 5.8 %; both p>0.05). The risk factors common to both tumor types were advanced age (>79 yr), pT stage, sex, and morbidity (each hazard ratio: >1; p<0.05)., Conclusions: MVR allows curation by R0 resection with adequate long-term survival. For colon or rectal CA, MVR tended to be associated with reduced 5-year overall survival rates (significant only for pT4 colon CA based on the MPA results), as well as, with a significant increase in morbidity rates in both tumor entities. In the overall data, MVR was associated with significant increases in hospital lethality rates, as indicated by the matched-pair analysis (significant only for rectal CA)., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: To investigate the influence of anastomosis on the early postoperative and long-term oncological outcomes of patients with primary colon carcinoma (CA)., Methods: All consecutive patients with the histologically diagnosed primary colon CA (design, prospective multicenter observational study) were registered with regard to patient-, diagnostic-, tumor (Tu) finding-, and treatment-related aspects using a computer-based registry with 60 items to characterize early postoperative and long-term oncological outcome., Results: Basic data : From 2010 to 2016, data from a total of 14,466 patients were documented (mean age, 72.8 [range, 22-96] years; sex ratio, m:f=7,696:6,770). - 717/14,466 patients (4.96 %) were included in a matched-pair analysis. The majority of these patients underwent elective surgery ( n =12,620 patients; 87.2 %) regardless of whether a bowel anastomosis or an ostomy was created. In emergency surgery, a bowel anastomosis was possible in a large proportion ( n =1,332 patients [72.1 %]). In contrast, in 514 patients (27.9 %) who underwent emergency surgery, an ostomy was created. Interestingly, ostomy had to be created even less frequently in patients who had undergone planned surgery ( n =366 [2.5 %]). - Early postoperative outcome : Cases of postoperative mortality were mainly due to general complications. Especially among the patients treated in an emergency situation without intestinal anastomosis, a high proportion died of their pre-existing condition (17.0 %). Patients who underwent ostomy creation or emergency surgery had a worse risk profile (incl. arterial hypertension, diabetes mellitus, and secondary cardiac or renal diseases) which led to the decision to operate without anastomosis. Furthermore, data show no matter which technique had been used, patients that had undergone surgical intervention without anastomosis were more likely to develop complications. - Long-term oncosurgical outcome : The most important factors influencing long-term survival were age, resection status, and tumor stage (according to TNM and UICC). The more advanced the tumor growth, the lower the long-term survival. Patients categorized with the same tumor stage, age, and risk factors had a better chance of survival, if they underwent elective surgical intervention and with intestinal anastomosis. Interestingly, the multivariable analysis showed that older patients and such with distant metastasis benefit from a discontinuity resection., Conclusions: The association of intraoperative and postoperative complications with increased postoperative mortality, as well as preexisting risk factors and perioperative complications is in line with findings of current studies. Furthermore, current studies also agree that older patients and such with reduced general condition benefit from discontinuity resection., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: For years, many efforts have been invested to prepare patients, in particular, those with reduced physical and psychic status, much better to provide and finally achieve better outocme if there is time available to provide several beneficial measures., Methods: Therefore, the objective was to illustrate the concept and various single elements of a complex prehabilitation concept based on (i) selective references from the medical literature and (ii) own clinical experiences from clinical practice in general and abdominal surgery., Results: Prehabiliation can be considered the solution of the efforts to improve preoperative status for patients in a disadvantageous status for almost all types of surgery and all other operative and/or interventional procedures. It is the targeted process to improve individual functionality and organ function before a planned (elective) surgical intervention; P. comprises basically nutritional, physical and psychological measures; P. focusses especially onto the elderly, frail and malnourished patients before a planned surgical intervention; the overall aim is to significantly improve final outcome characterized by shorter length of stay, lower complication rate and mortality as well as cost efficiency; P. is especially important in cancer surgery, in which the beneficial effects can be particularly implemented; P. programs and/or "Standard Operating Protocols" (SOP) may help to establish and materialize its single aspects and enhanced recovery after surgery (ERAS). There is still further potential to reliably establish and to utilize the options of prehabilitation measures as listed above., Conclusions: Prehabiliation is an indispensable aspect in today's preparation for elective surgery, which needs to become obligatory part of the preparation measures to planned surgical interventions, which can further contribute to a better final outcome and ERAS as well as, in addtion, needs to be further developed and accomplished., Competing Interests: Competing interests: No conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: Patients with different diseases may show signs of malnutrition both before and during the hospital stay. The presence of malnutrition may impact the recovery and length of stay and consequently the costs. Early identification of malnutrition is thus a critical factor. The objective of this multicenter study is to determine the prevalence of malnutrition in colorectal cancer centers. Another objective is to investigate possible consequences, such as complications or length of stay. In addition, the study aims to demonstrate the relevance of nutrition management in colorectal cancer centers. At the same time, relevant requirements clearly demanded by the Certification Commission for Certified Colorectal Cancer Centers are met through implementation of the study., Methods: Between 2019 and 2021, patients in colorectal cancer centers were examined in the preoperative phase. In addition to questions about patients' state of health and nutrition, the validated screening forms-Subjective Global Assessment (SGA) and Nutritional Risk Screening Tool 2002 (NRS 2002)-were used to assess malnutrition. The data were processed by univariate analysis., Results: In total, data records of 3,102 patients were evaluated. The mean age of the participants was 68.5 ± 11.9 years, and their average body mass index (BMI) was 26.8 ± 5.3 kg/m 2 . The SGA questionnaire indicated that 23 % of the participants suffered from malnutrition and 38 % were at risk of malnutrition (NRS≥3). Malnutrition was found more frequently in patients with colorectal carcinomas than in patients with rectal carcinomas (53.1 vs. 32.1 %). The length of stay in hospital and the rate of complications were significantly higher when malnutrition was identified., Conclusions: Approximately one in three to four patients with a colorectal carcinoma has an increased risk of malnutrition. The two screening methods calculated a different prevalence (23 and 38 %). Any malnutrition that is present demonstrably has a significant impact both on the rate of complications and the length of stay and may therefore have a decisive influence on the costs. The results of this multicenter study underscore the need for systematic screening for malnutrition and at the same time should increase clinics awareness of the importance of establishing a nutrition management policy., Competing Interests: Competing interests: The survey was supported by Wisswerk, as a Department of PubliCare GmbH, Cologne. Karsten Ridwelski received honoraria from B.Braun AG and the German Society of Surgery. Carl Meißner received honoraria from B.Braun AG, Nutricia, Fresenius, and PubliCare GmbH., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture., Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO., Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level., Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO., Funding: German Research Foundation (DFG)., Competing Interests: Declaration of interests MDR reports consulting fees from Roche Diagnostics and Medtronic; leadership or fiduciary role in the European Society of Gastrointestinal Endoscopy (ESGE) and World Endoscopy Organization (WEO). All other authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: With growing emphasis on surgical safety, it appears fundamental to assess the safety of colorectal resection involving primary stapled anastomosis. Surgical stapling devices can considerably foster patient safety in colorectal surgery, but their misuse or malfunction encompass a unique risk of postoperative complications. The Digital Device Briefing Tool (DDBT) is a digital cognitive aid developed to enhance safe use of the Ethicon circular stapling device during colorectal resection. The purpose of this study is to evaluate how a digital operative workflow, including DDBT, compared with routine surgical care, affects morbidity and mortality in patients undergoing left-sided colorectal resection with primary stapled colorectal anastomosis for colorectal cancer or benign disease., Methods and Analysis: A multicentre, prospective cohort study will be conducted at five certified academic colorectal centres in Germany. It compares a non-digital with a Johnson & Johnson digital solution (Surgical Process Institute Deutschland (SPI))-guided operative workflow in patients undergoing left hemicolectomy, sigmoidectomy, anterior rectal resection and Hartmann reversal procedure. The sample size is set at 528 cases in total, divided into 3 groups (a non-digital and two SPI-guided workflow cohorts, with and without DDBT) in a ratio of 1:1:1, with 176 patients each. The primary endpoint is a composite outcome comprising the overall rate of surgical complications, including death, during hospitalisation and within the first 30 days after colorectal resection. Secondary endpoints include operating time, length of hospital stay and 30-day hospital readmission rate., Ethics and Dissemination: This study will be performed in line with the Declaration of Helsinki. The ethics committee of the Charité-University Medicine Berlin, Germany, approved the study (No: 22-0277-EA2/060/22). Study Investigators will obtain written informed consent from each patient before a patient may participate in this study. The study results will be submitted to an international peer-reviewed journal., Trial Registration Number: DRKS00029682., Competing Interests: Competing interests: CL, PMC and GR are employees of Johnson & Johnson. JL, KB, AH, RSC, KR, CK and MK report no competing interests related to the manuscript., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings., Methods: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis., Results: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26)., Conclusion: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC., (© 2022. The Author(s).)

Purpose: To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer., Methods: This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H 0 ), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H 0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable., Results: Two-year OS was 71% in arm A (95% CI: 55-87%) vs. 53% in arm B (95% CI: 36-71%); H 0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30-1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25-1.04) for progression, 0.43 (0.13-1.40) for locoregional failure, and 0.43 (0.17-1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044)., Conclusion: Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

Objectives: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study., Methods: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire., Results: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p  = 0.001)., Conclusions: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10 -04 ) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10 -09 ). On chromosome 5p13 we found cis-eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10 -11 ). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10 -47 ). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10 -09 ). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims: Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients., Method: Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin., Results: Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis., Conclusion: In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

Background: Postoperative relapse rate after gastrectomy and perioperative chemotherapy remain high in patients with advanced gastric cancer due to the spread of disseminated tumour cells in the peritoneal cavity. Perioperative administration of catumaxomab could potentially eliminate residual tumour cells after intended curative resection of the primary tumour., Methods: This open-label, phase II study investigated the safety and efficacy of catumaxomab following neoadjuvant chemotherapy and subsequent surgery in patients with resectable (T2-4, N+, M0) gastric adenocarcinoma. Patients received catumaxomab intra- (single 10 μg dose) and postoperatively (10, 20, 50 and 150 μg on days 7, 10, 13 and 16, respectively). The primary endpoint was the postoperative complication rate (maximum rate defined as <62 %) within 30 days after surgery in patients who received at least the first catumaxomab dose., Results: Of 64 patients treated with neoadjuvant chemotherapy, 58 underwent surgery and 54 received at least the first catumaxomab dose. Postoperative complications were reported in 18 of 54 evaluable patients (complication rate 33 %; 95 % confidence interval: 21-48 %); thus, the primary endpoint was met. The most frequent complications were pulmonary infection (17 %) and anastomosis insufficiency requiring surgery (11 %). The most common catumaxomab-related adverse events were pyrexia (67 %), leucocytosis (19 %), abdominal pain (17 %) and chills (17 %). The 4-year disease-free and overall survival rates were 38 and 50 %., Conclusion: Intra- and postoperative administration of catumaxomab as part of a multimodal treatment approach was feasible and tolerable in patients with advanced gastric cancer and should be further investigated in a randomised trial.

Perioperative treatment is a standard of care in locally advanced gastroesophageal cancer (GEC) (gastric adenocarcinoma and gastroesophageal junction (GEJ) adenocarcinoma). While preoperative treatment can be applied to the majority of patients, postoperative chemotherapy can be given only to a fraction. The NeoFLOT-study therefore investigates the application of prolonged neoadjuvant chemotherapy (NACT). Patients with T3, T4, and/or node-positive adenocarcinoma (GEC) were eligible for this multicenter phase II trial. NACT consisted of 6 cycles of oxaliplatin 85 mg/m(2) , leucovorin 200 mg/m(2) , 5-fluorouracil 2600 mg/m(2) and docetaxel 50 mg/m(2) (FLOT) applied q 2 wks. Application of adjuvant chemotherapy was explicitly not part of the protocol. R0-resection rate was evaluated as a primary endpoint. Of 59 enrolled patients, 50 patients underwent surgery and were assessable for the primary endpoint. R0-resection rate was 86.0% (43/50). Pathologic complete response (pCR) was 20.0% (10/50) and a further 20% (10/50) of patients achieved near complete histological remission (<10% residual tumor). Among these very good responders, 85% (17/20) had intestinal type tumors, 10% (2/20) had diffuse and 5% (1/20) had mixed type tumors. After 3 cycles of NACT, 6.9% (4/58) of patients developed progressive disease. Median disease-free survival was 32.9 months. The 1-year survival-rate was 79.3%. Grade 3-4 toxicities included neutropenia 29.3%, febrile neutropenia 1.7%, diarrhea 12.1% and mucositis 6.9%. This study indicates that intensified NACT with 6 cycles of FLOT is highly effective and tolerable in resectable GEC. Very good response (pCR and <10% residual tumor) was predominantly observed in patients with intestinal type tumors., (© 2014 UICC.)

Importance: The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated., Objective: To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival., Design, Setting, and Patients: CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012., Interventions: After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone., Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up., Results: A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%)., Conclusions and Relevance: Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting., Trial Registration: isrctn.org Identifier: ISRCTN34802808.

Objective: Acute cholecystitis is a common disease, and laparoscopic surgery is the standard of care., Background: Optimal timing of surgery for acute cholecystitis remains controversial: either early surgery shortly after hospital admission or delayed elective surgery after a conservative treatment with antibiotics., Methods: The ACDC ("Acute Cholecystitis-early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy") study is a randomized, prospective, open-label, parallel group trial. Patients were randomly assigned to receive immediate surgery within 24 hours of hospital admission (group ILC) or initial antibiotic treatment, followed by delayed laparoscopic cholecystectomy at days 7 to 45 (group DLC). For infection, all patients were treated with moxifloxacin for at least 48 hours. Primary endpoint was occurrence of predefined relevant morbidity within 75 days. Secondary endpoints were as follows: (1) 75-day morbidity using a scoring system; (2) conversion rate; (3) change of antibiotic therapy; (4) mortality; (5) costs; and (6) length of hospital stay., Results: Morbidity rate was significantly lower in group ILC (304 patients) than in group DLC (314 patients): 11.8% versus 34.4%. Conversion rate to open surgery and mortality did not differ significantly between groups. Mean length of hospital stay (5.4 days vs 10.0 days; P < 0.001) and total hospital costs (€2919 vs €4262; P < 0.001) were significantly lower in group ILC., Conclusions: In this large, randomized trial, laparoscopic cholecystectomy within 24 hours of hospital admission was shown to be superior to the conservative approach concerning morbidity and costs. Therefore, we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients. (NCT00447304).

Background and Study Aims: This multicenter, prospective, country-wide quality-assurance study at more than 300 hospitals in Germany was designed to characterize and analyze the diagnostic accuracy of rectal endoscopic ultrasound (EUS) in the routine clinical staging of rectal carcinoma (depth of tumor infiltration)., Patients and Methods: Patients were surveyed between 1 January 2000 and 31 December 2008. Those who received neoadjuvant therapy after EUS were excluded. The correspondence between the EUS assessment of tumor depth (uT) and that determined by histology (pT) was calculated, and the influence of hospital volume upon the sensitivity, specificity, and positive and negative predictive values was investigated., Results: At 384 hospitals providing care at all levels, 29 206 patients were included; of the 27 458 treated by surgical resection, EUS was performed for 12 235 (44.6 %). Of these, 7096 did not receive neoadjuvant radiochemotherapy, allowing a uT-pT comparison. The uT-pT correspondence was 64.7 % (95 % confidence interval [CI] 63.6 % - 65.8 %); the frequency of understaging was 18 % (95 %CI 17.1 % - 18.9 %) and that of overstaging was 17.3 % (95 %CI 16.4 % - 18.2 %). The kappa coefficient was greatest in the category T1 (κ = 0.591). For T3 tumors κ was 0.468. The poorest correspondence was found for T2 and T4 tumors (κ = 0.367 and 0.321, respectively). A breakdown by hospital volume showed that the uT-pT correspondence was 63.2 % (95 %CI 61.5 % - 64.9 %) for hospitals undertaking ≤ 10 EUS/year, 64.6 % (95 %CI 62.9 % - 66.2 %) for doing 11 - 30 EUS/year, and 73.1 % (95 %CI 69.4 % - 76.5 %) for those hospitals performing > 30 EUS/year., Conclusions: In clinical routine, the diagnostic accuracy of transrectal ultrasound in staging rectal carcinoma does not attain the very good results reported in the literature. Only in the hands of diagnosticians with a large case volume of rectal carcinoma patients can EUS lead to therapy-relevant decisions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The occurrence of peritoneal carcinomatosis after resection of colorectal carcinoma is still a major concern. In this study, we tested the cytostatic agent oxaliplatin delivered intraperitoneally and intravenously to prove whether it can significantly reduce intraperitoneal tumor growth., Methods: Peritoneal tumor growth was experimentally induced with transfer of CC-531 colon cancer cells (5 x 10(6)) to the peritoneal surface of rats via laparotomy. Oxaliplatin was delivered either intraperitoneally or intravenously. In group A, oxaliplatin was administered directly after tumor cell transfer. While oxaliplatin was applied in group B on days 5, 10, and 15 after tumor cell implantation, in group C, it was administered on days 10, 15 and 20. The rats were sacrificed on day 30 after tumor cell transfer. Tumor weight, relative increase in tumor mass, volume of malignant ascites and the number of tumor nodes were determined., Results: Oxaliplatin significantly inhibited tumor growth after direct (group A) and early postoperative application (group B) via the intraperitoneal route. The late postoperative administration of oxaliplatin (group C) did not cause a significant effect on peritoneal tumor growth as it did with the intravenous application mode in groups A, B, and C., Conclusions: In this experimental model, oxaliplatin was highly effective against intraperitoneal tumor spread but only with the intraperitoneal application route. Other cytostatic agents with different effector mechanisms should be combined with oxaliplatin to further increase the therapeutic efficacy of the favorable intraperitoneal treatment in subsequent studies testing, in addition, the effects on wound and anastomosis healing., (Copyright (c) 2009 S. Karger AG, Basel.)

Background: Randomized studies proved the efficacy of new drugs for the systemic treatment of advanced gastric cancer in the past 5 years. However, little is known about the use of firstline chemotherapy in clinical practice in patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (AEG) and the stomach. We investigated temporal trends in therapy and factors influencing treatment decisions for these patients during a 4-year period., Patients and Methods: 1058 patients (median age 67 years) with advanced AEG or gastric cancers undergoing treatment decisions were documented with the Therapiemonitor® in 2006-2009. Therapiemonitor collects population-based data regarding treatment decisions and strategies. Time trends of drug use and intensity in the first-line treatment were analyzed in the entire patient group and according to age (cut-off 65 years) and Karnofsky performance status (KPS; cut-off 80%)., Results: Over time, the use of oxaliplatin and docetaxel as well as capecitabine increased while cisplatin and irinotecan use slightly declined. The use of chemotherapy triplets rose from 10.1% in 2006 to 47.0% in 2009. Treatment patterns significantly varied by age and KPS: Older patients were significantly less likely to receive chemotherapy triplets, cisplatin and docetaxel but tended to more often receive oxaliplatin. Likewise, triplets, cisplatin and docetaxel were less frequently used in patients with KPS < 80%, while capecitabine and irinotecan were significantly more often used in this patient group., Conclusions: A clear tendency towards the use of more intensive chemotherapy regimens in patients with AEG and gastric cancer was observed over time. Older or less fit patients were treated preferably with monotherapy or chemotherapy doublets during 2006-2009. Oxaliplatin and docetaxel use has substantially risen., (Copyright © 2010 S. Karger AG, Basel.)

Background: Development of incisional hernia after open abdominal surgery remains a major cause of post-operative morbidity. The aim of this study was to determine the current practice of surgeons in terms of access to and closure of the abdominal cavity in elective open surgery., Methods: Twelve surgical departments of the INSECT-Trial group documented the following variables for 50 consecutive patients undergoing abdominal surgery: fascial closure techniques, applied suture materials, application of subcutaneous sutures, subcutaneous drains, methods for skin closure. Descriptive analysis was performed and consensus of treatment variables was categorized into four levels: Strong consensus >95%, consensus 75-95%, overall agreement 50-75%, no consensus <50%., Results: 157 out of 599 patients were eligible for analysis (85 (54%) midline, 54 (35%) transverse incisions). After midline incisions the fascia was closed continuously in 55 patients (65%), using slowly absorbable (n = 47, 55%), braided (n = 32, 38%) sutures with a strength of 1 (n = 48, 57%). In the transverse setting the fascia was closed continuously in 39 patients (72%) with slowly absorbable (n = 22, 41%) braided sutures (n = 27, 50%) with a strength of 1 (n = 30, 56%)., Conclusion: In the present evaluation midline incision was the most frequently applied access in elective open abdominal surgery. None of the treatments for abdominal wall closure (except skin closure in the midline group) is performed on a consensus level.

Background: The prognostic impact of isolated lymphovascular invasion (LVI) after radical resection of rectal cancer is controversially discussed. However, it could be relevant to decide for an adjuvant treatment., Aim: The aim of the analysis was, based on the data of an observational study, to determine the prognostic relevance of the isolated LVI., Materials and Methods: Patients after radical resection of rectal cancer with no hemangioinvasion were subdivided in three groups: I-no LVI, no lymph node metastases (LNM); II-positive LVI, no LNM; III-positive LNM. Five-year local recurrence rate, distant metastases-free and disease-free survival were determined uni- and multivariate., Results: Patients, n = 846, were studied (I, n = 471; II, n = 75; III, n = 300). The univariate comparison between the groups revealed the following 5-year results: local recurrence rate: 9.4 vs 10.0 vs 14.0%; distant metastases-free survival: 84.1 vs 82.5 vs 49.3%; disease-free survival: 83.2 vs 80.7 vs 45.5%. The differences between groups I and III were significant, but not between groups I and II. The determined higher disease-free survival rate in group II vs group III was significant (P = 0.041), but the differences in local recurrence rate and rate of distant metastases did not reach statistical significance. The multivariate analysis revealed no impact of the isolated LVI on the oncological outcome., Conclusion: The isolated LVI has no independent prognostic impact on the local recurrence rate and long-term survival after radical resection of rectal cancer. Based on this finding, no indication for an adjuvant treatment in these patients can be derived.

Context: The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists., Objective: To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more., Design, Setting, and Patients: Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups., Intervention: Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175)., Main Outcome Measures: Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat)., Results: More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank)., Conclusions: Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas., Trial Registration: isrctn.org Identifier: ISRCTN34802808.

Background: The optimum regimen for advanced gastric cancer requires definition. This multicentre phase II study evaluated docetaxel-cisplatin combination in advanced gastric cancer., Methods: Chemotherapy-naive patients with locally advanced or metastatic disease received docetaxel plus cisplatin (75/75 mg/m(2)) every 21 days for up to 9 cycles. Endpoints included tumour response, time to progression, overall survival and toxicity., Results: Of 113 patients recruited, 88 were completely evaluable. The median age was 58 years, and most patients had metastatic disease. The overall response rate was 29.6%. Five patients (5.7%) achieved a complete response and 21 patients (23.9%) had a partial response. Tumour control, including stable disease, was achieved in 57 patients (64.8%). The median time to progression and median overall survival time was 4.8 and 8.7 months, respectively. The major toxicity was haematological: 37.5% of patients experienced grade 3-4 neutropenia, whereas febrile neutropenia was observed in only 2% of patients., Conclusion: Docetaxel-cisplatin was active with a predictable and manageable toxicity profile., ((c) 2007 S. Karger AG, Basel.)

Background: Recurrent tumor growth of colorectal carcinoma at the peritoneal site remains an unsolved problem. The aim of this study was to investigate whether the substance taxol (paclitaxel) can alter intraperitoneal tumor spread using different modes of drug application., Methods: Intraperitoneal tumor growth was induced using a tumor cell transfer model (10(6) cells) in rats divided into 3 groups: (1) taxol was applied directly into the abdominal cavity, intraperitoneally or intravenously, immediately following intraperitoneal tumor cell transfer; (2) early postoperative intraperitoneal and intravenous chemotherapy was administered on days 5, 10 and 15 after surgical intervention using an intraperitoneal or intravenous port-a-cath; (3) control group. Thirty days after tumor cell transfer, rats were sacrificed, and tumor weight, number of nodes (at greater omentum and peritoneum) and ascites volume were determined., Results: Taxol generated a significant inhibitory effect on peritoneal tumor growth. Direct intraoperative intraperitoneal application of taxol induced a more pronounced effect compared with early postoperative intraperitoneal application of the antineoplastic drug. Both application modes were superior to the intravenous route (no significant effect)., Conclusion: Taxol appears to be a potential chemotherapeutic drug providing a significant effect in the therapeutic management of peritoneal carcinomatosis under experimental conditions. Combination of taxol with cytostatic agents and new drugs generating different effector mechanisms may help to further diminish or even to prevent intraperitoneal tumor growth., ((c) 2007 S. Karger AG, Basel.)

Aims: To assess the maximum tolerability of a combined therapy regimen of gemcitabine and docetaxel, and to evaluate tumour response rate, survival time and tolerability in patients receiving these agents for advanced pancreatic carcinoma., Patients and Methods: Patients (n=68) with pancreatic carcinoma (advanced and/or unresectable tumour growth or histopathologically diagnosed metastases) were enrolled in a multicenter phase-I (n=25) and phase-II study (n=43). Treatment during phase II of the study was continued until either complete tumour remission (CR), tumour progression, indicated clinically or by means of radiological imaging, or until unacceptable toxicity occurred., Results: Phase I: the tolerability maximum of the combined agents was established at gemcitabine 1000 mg/m(2) and docetaxel 35 mg/m(2) with tolerable adverse events. Phase II: a total of 139 chemotherapy cycles were completed (mean, 3.2; range, 1-10). While CR was achieved in three of 43 patients (7%), in five further cases, partial remission (PR) was documented, amounting to an overall response rate (OR) of 18.6%. Eighteen patients showed stable disease (41.9%), whereas in 17 of 43 subjects (39.5%), primary tumour progression was detected. The median survival time was 9.0 months; the 1-year survival rate was 13.9% (six of 43 patients). These results were associated with a side-effect profile of moderate severity and acceptable quality of life (QOL)., Conclusion: The combination of gemcitabine and docetaxel for chemotherapy in unresectable pancreatic carcinoma was well tolerated. Survival time and 1-year survival rate proved promising and the regimen appears suitable for further evaluation in a prospective phase-III study setting.

Purpose: Peritoneal recurrence after resection of colorectal carcinoma is still a major concern. We investigated whether the novel cytostatic drug, CPT-11 (Irinotecan), delivered intraperitoneally (i.p.) and intravenously (i.v.), could inhibit intraperitoneal tumor spread in a rat model., Methods: We induced intraperitoneal tumor growth using a tumor cell transfer model (10(6) cells) and divided the rats into the following five groups of eight: group IP1, given CPT-11 i.p. immediately after intraperitoneal tumor cell transfer; group IV1, given CPT-11 i.v. immediately after intraperitoneal tumor cell transfer; group IP2, given CPT-11 i.p. on postoperative days (PODs) 5, 10, and 15; group IV2, given CPT-11 on PODs 5, 10, and 15; and a control group. The rats were killed 30 days after tumor cell transfer, and the tumor weight, number of nodes in the greater omentum and peritoneum, presence of metastases in the liver and lungs, and ascites volume were determined., Results: CPT-11 inhibited peritoneal tumor growth significantly. The direct intraoperative intraperitoneal application induced a more pronounced effect than the early postoperative intraperitoneal application, but both these application modes were superior to the intravenous route, which had no significant effect., Conclusion: CPT-11 was highly efficacious against peritoneal carcinomatosis in this experimental model. The combination of CPT-11 with other cytostatic agents and drugs generating different effector mechanisms may diminish or even prevent intraperitoneal tumor growth.

Purpose: Systemic palliative chemotherapy provides only a disappointing response and almost no prolongation of the survival time in patients with pancreatic carcinoma. Isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects. The aim of the study was to investigate the feasibility of the aortic stop-flow technique using commercially available tools in patients with advanced pancreatic carcinoma., Methods: Seventeen patients with either unresectable or metastasized pancreatic carcinoma (diagnosed by histologic investigation) were enrolled in the study. In total, a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 of mitomycin C (Medac, Hamburg, Germany) was carried out 22 times. The cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. The tumor response was assessed using computed tomography and a tumor marker (CA19-9) every 4 weeks., Results: While 12 patients underwent one cycle, in 5 patients two complete perfusions were performed. Mitomycin C concentration was 10-fold higher within the regional compared with the systemic compartment at its maximum. The area under the curve (AUC) was 4.02 times larger. The degree of toxicity was considerable: World Health Organization grade I/II in 8/17, III/IV in 9/17 cases. Three treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission [CR], 2 partial remissions [PR]). In 3 subjects, a stable disease (SD) and in 11 individuals tumor progression (PD) was registered. The median survival was 4.1 months., Conclusion: The aortic stop-flow technique was associated with a high toxicity rate but no improvement in the tumor response and survival was seen in comparison to the systemic chemotherapy of the historical group. Despite detectable pharmacokinetic advantages, the aortic stop-flow technique is therefore not considered to be feasible for palliative chemotherapy in patients with pancreatic carcinoma for routine use.

The objective of this study was to assess the efficacy and safety of two regimens of irinotecan, combined or alternated with bolus 5-fluorouracil (5-FU) and folinic acid (FA), and the Mayo Clinic regimen as first-line therapy for colorectal cancer (CRC). A total of 152 patients with advanced CRC were randomised, and 149 patients were treated intravenously by irinotecan 125 mg/m2, FA 20 mg/m2 followed by 5-FU 500 mg/m2 bolus, weekly for 4 weeks (arm A, Saltz regimen; n=46), or irinotecan 350 mg/m2 alternating with FA 20 mg/m2/day followed by 5-FU bolus 425 mg/m2/day for 5 days (arm B; n=53), or FA 20 mg/m2/ day followed by 5-FU bolus 425 mg/m2/day over 5 days every 4 weeks (arm C, Mayo Clinic regimen; n=50). Patients were analyzed for tumor response, time to progression, overall survival, safety and quality of life. The overall response rate for evaluable patients in arm A was 33% [95% confidence interval (CI), 17-49%], in arm B was 32% (95% CI, 16-49%) and in arm C was 26% (95% CI, 12-40%). Median times to progression were 7.9, 7.0 and 6.9 months and median survival times were 22.2, 17.0 and 18.2 months for arms A, B and C, respectively, in the intention-to-treat population. The main grade 3-4 adverse events were neutropenia (7%, 39% and 12%) and diarrhea (6%, 21% and 18%). In conclusion, both regimens containing irinotecan were active and well tolerated in patients with advanced CRC.

Background: In advanced pancreatic carcinoma, no effective chemotherapy has been found yet due to the lack of appropriate response. The frequent use of gemcitabine is based on the fact that there is a significant improvement in the quality of life, but neither an effect on remission nor a detectable increase in survival rates could be observed. Therefore, the hypothesis was that the combination of gemcitabine with other drugs can result in a better outcome of patients. The aim of this study was to determine the maximally tolerable dosage of gemcitabine and docetaxel using a weekly administration regimen., Patients and Methods: Twenty-five patients with advanced or metastatic pancreatic carcinoma received combination chemotherapy using gemcitabine and docetaxel in a weekly administration regimen, beginning with 800 mg/m2 of gemcitabine and 25 mg/m2 of docetaxel. Four patients were originally enrolled for each of the seven different dosages of both drugs. Side effects were assessed according to the WHO standard. Quality of life was evaluated according to the Core Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer., Results: Using the two maximal dosages of gemcitabine and docetaxel (gemcitabine, 800 and 1,000 mg/m2, and docetaxel, 45 and 40 mg/m2; respectively), only 3 and 2 patients were enrolled, respectively, because of toxic side effects > or = grade III according to WHO grading. Maximal dosages with tolerable side effects were 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel given in weekly intervals. Main side effects of this combination chemotherapy were gastrointestinal symptoms and hematologic toxicity., Conclusion: Combination therapy with gemcitabine and docetaxel in advanced or metastatic pancreatic carcinoma is a well-tolerated and acceptable alternative treatment option with regard to the severity of side effects and its positive impact on quality of life and tumor-associated pain. According to the study endpoint, dosages of 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel are recommended as maximum-tolerated doses (given in weekly intervals) for a future phase II trial., (2004 S. Karger AG, Basel.)

Background: Locoregional intra-arterial (i.a.) chemotherapy may provide high levels of cytostatic concentrations within the tumour and, simultaneously, a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. In addition, this may lead to an increase of tumour response rate and prolongation of survival time. The aim of the study was (1) to evaluate the benefit of an i.a. infusion of cytostatic drugs via the coeliac trunk on tumour response rate and survival time, (2) to elucidate problems and risks, and finally (3) to achieve an improvement of overall therapeutic management in pancreatic carcinoma., Patients and Methods: In 22 patients (12 female; 10 male; mean age 57.1 years) with locally advanced pancreatic carcinoma, which was confirmed by histopathology, i.a. chemotherapy was administered. Through a catheter, which was inserted via the femoral artery by the Seldinger technique and placed with the tip in the coeliac trunk, two different drug combinations were given. Group A ( n=12) were given a bolus injection of a mixture (chemo-occlusion) consisting of amilomer (Spherex) and epirubicin (Farmorubicin) followed by short-time infusion of folic acid and 24-h infusion of 5-FU. Group B ( n=10) were given treatment over 5 days: mitoxantrone (Novantrone, day [d] 1), 5-FU and folic acid (Haemato-folin, d 2-4), and cisplatin (d 5). Treatment was repeated in both groups every 4 weeks. Tumour response was assessed by computed tomography every 8 weeks., Results: In group A, there was one complete and one partial remission, resulting in a remission rate of 16.6%. Two patients showed stable disease, while in two-thirds of the patients ( n=8), progressive disease was found. Median survival time was 3 months; 1-year survival rate was 33.3% (4 of 12 patients). In group B, again, one complete and one partial remission were observed (remission rate 20%). In three cases, stable disease, and in 50% of patients ( n=5), progressive disease, were documented. Median survival was 7.0 months; 1-year survival rate was 20% (2 of 10 patients). If both groups were compared, there was no difference in survival. In addition, no prolongation of survival time was found in comparison with patients of a historical study group treated with established systemic chemotherapy using gemcitabine monotherapy ( n=28; median survival time 9 months). Though a tendency for poorer outcome of i.a. chemotherapy was seen when the Kaplan-Meier curves of survival were compared, this difference was not statistically significant (log rank test, P=0.08)., Conclusion: Despite conceptual and pharmacokinetic advantages of locoregional i.a. chemotherapy, better outcome with regard to tumour response rate and survival time could not be found. I.a. chemotherapy is, therefore, still an experimental treatment option in pancreatic carcinoma and can, currently, not be recommended for routine use.

Following resection of colorectal carcinoma, a considerable local recurrence rate within the previous tumor bed or at the peritoneal site remains an unsolved problem. Currently, there are no established protocols for the treatment or prevention of peritoneal carcinomatosis. Taxol showed benefit in patients with advanced tumor growth, in particular, gynecological carcinomas. Taxol was used to test whether it can either prevent or treat peritoneal tumor growth derived from colon carcinoma. In rats divided in 3 groups, peritoneal carcinomatosis was induced by tumor cell transfer: Taxol (170 mg/m(2)) was given i). directly (group A); ii). on days 5, 10, 15 postoperatively (representing early administration; group B), or iii). as late intraperitoneal (i.p.) chemotherapy (15, 20, 25 days following surgery; aiming for reduction of a manifest peritoneal carcinomatosis; group C) into the abdominal cavity. Tumor growth was quantified by tumor weight of the greater omentum and the mesenteric site, number of detectable tumor lesions, occurrence of hepatic and pulmonary metastases and the amount of ascites. Taxol was highly effective in preventing or reducing i.p. tumor spread when the drug was given directly or within a short time interval after tumor cell implantation (groups A and B), whereas no significant antineoplastic potential was found in the treatment of an established peritoneal carcinomatosis. In conclusion, Taxol appears to be a promising chemotherapeutic agent to be investigated in further detail with possible potential for a later human phase-I trial in peritoneal carcinomatosis.

Purpose: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV., Patients and Methods: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point., Results: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms., Conclusion: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.

Purpose: Neoadjuvant chemotherapy in locally advanced gastric cancer is effective, but is often associated with severe side effects, including fatal outcome. This study evaluates a combination of cisplatin, folinic acid and 5-fluorouracil (PLF) in terms of efficacy (R-0 resection rate) and toxicity., Methods: Twenty-five patients with locally advanced gastric cancer who after extensive staging were deemed not suitable for curative resection underwent neoadjuvant chemotherapy. Three or four cycles of cisplatin (50 mg/m(2) days 1 and 15), folinic acid (200 mg/m(2) days 1, 8, 15 and 22), and 5-fluorouracil (2,000 mg/m(2 ) days 1, 8, 15 and 22) were administered. Cases with progressive disease were taken off the study. Two weeks after finishing chemotherapy resection was performed and all patients were enrolled in a structured follow-up., Results: Of the patients, 22/25 finished chemotherapy and 20 of those underwent laparotomy. In 13/25 patients (52%) a R-0 resection and in three cases a R-1 resection were achieved. Four patients stayed irresectable. During 76 completed cycles of chemotherapy we observed five cases of WHO grade-III toxicity and no grade-IV toxicity., Conclusions: The presented PLF protocol yields R-0 resection rates comparable to protocols like EAP (etoposide, adriamycin, platinum), but with a better safety profile allowing administration in an outpatient setting. Our study supports PLF as a reference neoadjuvant treatment for gastric cancer even outside of clinical studies.

Purpose: Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases., Patients and Methods: 42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion., Results: An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications., Conclusion: The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.

Purpose: The prognosis of patients with biliary tree carcinomas is very poor. The diagnosis often occurs at an advanced stage, when curative resection is not possible. We combined gemcitabine and docetaxel to optimize the palliative therapy for patients with gallbladder, biliary, and cholangio-carcinomas on an outpatient basis., Patients and Methods: Patients with histologically proven biliary tree carcinomas and a WHO performance status <2 received gemcitabine 1000 mg/m2 followed by docetaxel 35 mg/m2 weekly for 3 weeks followed by I week of rest., Results: Forty-three patients, 14 males/29 females, with an average age of 63.3 years (range, 41 to 78) have been enrolled since 1998; 37 have completed treatment. So far, 168 cycles (range, 1 to 16) have been administered. All 43 patients were included in the response and toxicity assessments. There are no complete remissions; however, 4 (9.3%) patients achieved partial remission, 1 (2.3%) had a minimal remission, and 24 (55.8%) reached disease stabilization for a median period of 5.2 months. Fourteen (32.6%) patients progressed. The median overall survival rate is currently 11.0 months. Grade 3 hematologic toxicities were infrequent, and there were no grade 4 hematologic toxicities. Grade 3 leukopenia was reported in 4 (9.3%) patients, grade 3 thrombozytopenia in 1 (2.3%) patient, and grade 3 anemia in 1 (2.3%) patient. Twenty-eight (65.1%) patients had grade 3/4 alopecia, 8 (18.6%) had nausea/vomiting, and 2 (4.6%) had mucositis., Conclusion: The combination of gemcitabine/docetaxel is an effective and well tolerated therapy for patients with advanced or metastatic gallbladder, biliary, and cholangio-carcinomas.

Following surgical resection of colorectal carcinoma, local recurrence in the tumor bed or in the mesentery remains a frequently encountered problem. Currently there are no recognized standard therapy protocols for the prevention of local recurrence or the treatment of peritoneal carcinomatosis. The aim of our trial was to investigate whether CPT-11 and oxaliplatin could decrease i.p. tumor growth in a basic experimental animal model. Experiments were performed on three groups of animals plus controls. In the first group, the cytostatic agents were applied directly following tumor cell implantation into the peritoneal cavity. In the second group, early postoperative i.p. chemotherapy (days 5, 10 and 15 following surgery) was administered. In the third group, late i.p. chemotherapy (days 15, 20 and 25 after tumor cell transfer) was administered with the intention of reducing a manifest peritoneal carcinomatosis. The trial also set out to describe any side effects observed following i.p. administration. The results indicated that CPT-11 and oxaliplatin were highly effective in reducing i.p. tumor spread after direct i.p intraoperative application. Intraperitoneal administration of CPT-11 or oxaliplatin also decreased i.p. tumor growth after early i.p. chemotherapy. CPT-11 was a little more effective with lower side effects. However, it was clear that it was not possible to treat a manifest peritoneal carcinomatosis in this way.

Patients with International Union Against Cancer (UICC) stage IIb and III colon cancer and stage II and III rectal cancer may receive adjuvant chemotherapy with 5-fluorouracil (5-FU). High levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been associated with resistance to 5-FU in advanced colorectal cancer. The aim of this study was to investigate the association of TS and DPD mRNA levels with recurrence-free survival in patients with colorectal cancer who are receiving adjuvant 5-FU-based chemotherapy. TS and DPD mRNA quantitation was retrospectively performed in primary colorectal cancer specimens from patients receiving adjuvant 5-FU using a reverse transcription- polymerase chain reaction technique. The median TS mRNA level in patients with a recurrence (n = 142) was 0.68, and in patients without a recurrence (n = 206) the median level was 0.80 (P < 0.01). Patients with a recurrence who had a low TS level (TS < or = 0.9; n = 102) had a median recurrence-free survival of 18 months (range 3.0 to 54 months), and those with a high TS level (TS > 0.9; n = 40) had a median recurrence-free survival of 11 months (range 1.7 to 53 months; P = 0.0024). There was no difference in the median recurrence-free survival of patients with low and high DPD mRNA levels. The TS mRNA level may be a useful marker to predict the time to recurrence in patients with colorectal cancer who are receiving adjuvant 5-FU treatment.

Gastric stromal tumors are solitary, usually asymptomatic, lesions that can bleed, become obstructive, or even degenerate into malignant neoplasms. Therefore, their surgical excision is recommended. We report a technique for the successful resection of a stromal tumor of the posterior gastric wall using a transgastric approach. After the creation of a 12 mmHg pneumoperitoneum using a three-trocar technique, a 2-cm gastrostomy was performed; an 18-mm trocar was then positioned in the gastric lumen and secured with a pursestring suture. Next, an intragastric wedge resection of the posterior gastric wall was carried out under endoscopic guidance. Finally, the anterior gastric wall was closed using a linear stapler. Histopathological analysis showed a benign spindle cell tumor, which was excised in toto. Patient recovery was uneventful. This report supports previous data showing the feasibility of a laparoscopic transgastric approach for the resection of stromal tumors of the posterior gastric wall. It also underscores the synergy of laparoscopic and endoscopic procedures in minimally invasive gastric surgery.

Background and Objectives: Malignant tumors of various abdominal organs are blamed to be the cause of death in approximately 40% of cases per year in Western Europe. At the time of death, about half of them show peritoneal carcinomatosis which is considered an unfavorable prognostic factor. In case of peritoneal carcinomatosis, there is no curative treatment available for any of the tumors in the abdominal cavity. The aim of this experimental study was to evaluate the preventive potential of intra-operative or early postoperative local administration of gemcitabine into the abdominal cavity against peritoneal carcinomatosis., Methods: Peritoneal carcinomatosis was induced in male WAG rats (n = 18) by transfer of 5 x 10(6) cells of the adenocarcinoma cell line CC-531 via minilaparotomy carried out in all rats under general anesthesia. Thirty days after cell transfer, rats were sacrificed and peritoneal carcinomatosis was confirmed using histologic investigation in specimens obtained from the peritoneal site. Extension of this carcinomatosis was quantified by (i) counting tumor nodes per square centimeter (mean of several counts) and (ii) determining tumor weight (weight of the greater omentum plus the resected mesentery). Rats were subdivided into three groups (n = 6 per group): group 1 (controls); group 2, simultaneously with tumor cell transfer 24 mg/kg of gemcitabine were administered into the abdominal cavity; group 3, postoperative intraperitoneal irrigation with 24 mg/kg of gemcitabine was achieved via a previously implanted port-a-cath on days(d) 15, 21, and 27., Results: On the 30th postoperative day, all six animals of the control group showed extensive tumor growth at the peritoneum and greater omentum, indicating carcinomatosis. In contrast, none of the rats of group 2 revealed any traces of intraperitoneal tumor growth. While all rats of group 3 demonstrated intraperitoneal tumor growth, but early postoperative treatment with gemcitabine, however, resulted in a significant reduction of the number of tumor nodes and tumor weight in comparison with group 1 (controls)., Conclusions: Immediate, i.e., simultaneous intraoperative application of a cytostatic agent such as gemcitabine into the abdominal cavity may completely prevent the generation of peritoneal carcinomatosis from occuring tumor cells, whereas early postoperative locoregional chemotherapy into the abdominal cavity can only reduce the severity of the peritoneal carcinomatosis., (Copyright 2002 Wiley-Liss, Inc.)

Background and Aims: We compared the effectiveness and side effects of various cytostatic agents for use in perioperative intraperitoneal irrigation to prevent peritoneal carcinomatosis., Methods: The adenocarcinoma cell line CC-531 was implanted during laparotomy at the mesenterial trunk of anesthetized male WAG rats. Direct perioperative intraperitoneal chemotherapy was performed after 5 min with either 5-fluorouracil, cisplatin, or mitomycin; controls received only tumor cells. The animals were inspected daily over 30 days for side effects. They were then killed, and the greater omentum and mesentery were resected, the tumor mass was examined for the presence of peritoneal carcinomatosis, and tumor nodules in the greater omentum and mesentery were counted., Results: All the animals in the control group developed histologically confirmed peritoneal carcinomatosis. Animals receiving cisplatin or mitomycin by direct intraperitoneal perioperative chemotherapy showed no macroscopic or histological evidence of tumor growth. Two animals in the fluorouracil group had macroscopically and histologically manifest tumor growth; another animal showed only histological evidence of malignancy. Substantial side effects were noted in the cisplatin group, with all animals experiencing bleeding in the peritoneum and toxic necrotic reactions of the colon; two animals died of these side effects., Conclusion: Direct intraperitoneal chemotherapy with cisplatin or mitomycin prevents peritoneal carcinomatosis in experimental investigations.

Leiomyosarcoma of the inferior vena cava is a rare mesenchymal tumor. The diagnostic approach, based on general guidelines of oncologic surgery, seems to be relatively routine; specific aspects of treatment, including vascular reconstruction, depend on tumor stage, grade, and location. In this report, the management of this disease in 5 patients is summarized and the literature is reviewed. A thorough diagnostic assessment includes sonography, computed tomography, angiography or duplex ultrasonography, perioperative pathohistologic examination, and appropriate differential diagnosis. Radical resection is associated with the best outcome and long-term survival. In this series, 4 of 5 patients underwent tumor resection. In 2 patients, the disease was classified as R0. Another patient had R1 status found at resection and underwent postoperative radiation after the tumor bed was marked intraoperatively. She has remained stable since treatment. One patient died of pulmonary metastases 32 months after primary R1 tumor resection. The 5th patient has been stable since diagnosis; resection was not possible because of severe accompanying diseases and because consent for surgical intervention could not be obtained from the patient. There is reasonable hope that leiomyosarcoma of the inferior vena cava can be treated successfully, even in advanced stages, with novel antineoplastic drugs and radiotherapeutic protocols. However, general treatment recommendations have not yet been compiled.

Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression., (Copyright 2001 S. Karger AG, Basel)

Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by multivariate analysis, followed by tumor stage (UICC) and preoperative appetite. Besides tumor-associated determinants, data from the medical history, and pathological laboratory parameters, the prognosis in pancreatic carcinoma is considerably determined by the treatment such as interventional and/or using antineoplastic agents., (Copyright 2001 S. Karger AG, Basel)

Background/aims: A prerequisite for successful laparoscopic cholecystectomy is the exclusion of potential risks such as cholangiolithiasis, anatomical malformations or diseases of the stomach. As there is no general agreement regarding the appropriate preoperative diagnostic workup, we compared different diagnostic methods as to their value in detecting unknown accompanying diseases and complications., Methodology: Between 9/90 and 8/93, we performed 850 laparoscopic cholecystectomies. The first 700 were included in this study. A prospective comparison was carried out of the diagnostic accuracy of history, physical examination, laboratory tests, upper gastrointestinal endoscopy or barium meal, i.v. cholangiography and abdominal ultrasound., Results: Measurement of the diameter of the common bile duct was found to be a good noninvasive method for diagnosing common bile duct stones (sensitivity 80%, specificity 99%). In combination with the history and the laboratory tests the sensitivity could be improved to 99%. The sensitivity of i.v. cholangiography in detecting common bile duct stones was 80%, the specificity 99.3%. 646/700 patients underwent preoperative endoscopy/barium meal. In 53 (8.2%) patients pathological findings were found, but only in 4 cases (0.6%) they influenced the indication for laparoscopic cholecystectomy. In 1 patient an advanced gastric cancer was diagnosed 6 months after laparoscopic cholecystectomy, the preoperative barium meal did not show any pathological findings., Conclusions: The results show that routine ultrasonography in combination with history and laboratory tests prior to laparoscopic cholecystectomy can be recommended for detecting common bile duct stones. In patients with 1 or more pathologic finding endoscopic retrograde cholangiopancreatography should be performed preoperatively. A gastroscopy should be done in patients with nonspecific upper abdominal pain, history of peptic ulcer disease and persisting pain after laparoscopic cholecystectomy.

Background: Poor treatment results obtained with palliative chemotherapy for advanced gastric cancer indicate the need for new effective and well-tolerated regimens., Patients and Methods: Forty-three patients with locally advanced or metastatic gastric cancer were enrolled in a phase II study to evaluate the efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and cisplatin 75 mg/m2 given every three weeks., Results: Thirty-nine patients were evaluable for response. Four achieved a complete response and twelve a partial response, for an overall response rate of 37.2% (16 of 43 patients; 95% confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months and median overall survival 10.4 months. Forty-two percent of all patients were still alive at one year and twelve percent at two years. The major toxicity was leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no febrile neutropenia occurred. Non-haematological toxicities were usually mild to moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral neuropathy developed after completion of chemotherapy in two patients., Conclusions: These results suggest that the combination of docetaxel and cisplatin has moderate toxicity and is an effective regimen for the treatment of advanced gastric cancer, both with regard to response rate and survival.

A 59-year-old woman presented with epigastric pain and weight loss. Ultrasound, computed tomography, and magnetic resonance imaging scans of the abdomen showed a tumor in segments 6 and 7 of the right liver lobe, measuring 8 cm in greatest diameter. The tumor was subsequently resected, and histopathology showed a poorly differentiated adenocarcinoma immunoreactive for CA 19-9 and cytokeratin 19. In the absence of any other clinically detectable primary tumor, the lesion was diagnosed as a peripheral intrahepatic cholangiocarcinoma. In addition, multiple bile duct hamartomas were found in the surrounding parenchyma. The tumor was unrelated to Caroli disease, primary sclerosing cholangitis, ulcerative colitis, or nonbiliary cirrhosis, as demonstrated by further clinical and histopathologic investigations, but probably was associated with the presence of multiple bile duct hamartomas. To our knowledge, this is the eighth reported case of a cholangiocarcinoma associated with multiple bile duct hamartomas.