Background In the last decade, neoadjuvant chemotherapy has become the standard of care also for curatively resectable advanced gastric cancer. Prospective randomized studies have shown a significant benefit in disease free and overall survival rate after perioperative chemotherapy as compared to immediate surgery. However, data in the real-life setting are rare. In our retrospective study, we wanted to clarify the question whether this benefit is achievable under real-life conditions. Methods A total of 81 patients with resected adenocarcinoma of the stomach or distal esophagogastric junction (AEG III) clinical stage II-IIIc according to UICC (eighth edition) were enrolled. Forty-two patients received perioperative chemotherapy (cohort 1) and 39 patients were operated on immediately (cohort 2). Chemotherapy was carried out according to the ECF, EOX, or FLOT protocols. Results Overall 5-year survival was 35.7% in cohort 1 and 23.7% in cohort 2. Thus, the relative 5-year overall survival benefit was 51%, and 12% in absolute numbers (p=0.083). For patients receiving perioperative chemotherapy per protocol (n=20), a more marked absolute improvement in 5-year overall survival of 16.3% as compared to immediately operated on patients was achieved (p=0.05). Progression-free survival in this analysis was shown to be improved by perioperative chemotherapy also without statistical significance (p=0.03). Conclusions Patients with curatively resectable gastric adenocarcinoma or type III AEG tumor benefit from perioperative chemotherapy in terms of overall survival even under real-life conditions. Moreover, a benefit in progression-free survival can be demonstrated.

Hintergrund/Einleitung: Nach Anlage eines ileoanalen Pouches (IAP) entwickeln im weiteren Verlauf ca. 10–40% der Pat. mit Colitis ulcerosa (CU), aber weniger als 5% der Patienten mit Polyposis coli (FAP) eine Pouchitis. Ungeklärt ist die Frage, ob es sich bei der Pouchitis um ein Wiederauftreten der Grunderkrankung im Pouch oder aber um eine eigene CED-Entität handelt. Wir charakterisierten daher die Zytokin- und Chemokin-Transkriptprofile in entzündeten und nicht-entzündeten Pouches von Patienten mit CU, M. Crohn (MC) und FAP.

Hintergrund/Einleitung: Die Korrektur von Fehlern bei der Replikation der DNA (Mismatches) erfolgt durch ein konserviertes System (Mismatch Reparatur), welches für die Replikationsgenauigkeit bei der DNA-Synthese entscheidend ist. Beim Menschen wird die Korrektur vor allem durch die Proteinheterodimere hMutSa (hMSH2-hMSH6) und hMutLa (hMLH1-hPMS2) initiiert. Defekte in diesem System stellen die Grundlage für das hereditäre nicht-polypöse kolorektale Karzinom (HNPCC) dar.

Einleitung: Etwa 25% aller kolorektalen Karzinome (KRK) entfallen auf Verwandte von Betroffenen. Die Prävalenz kolorektaler Adenome bei 50–60-jährigen Verwandten von KRK-Trägern reicht von 17–34%. Unser Ziel war die Bestimmung der Prävalenz von kolorektalen Adenomen bei 40–50-jährigen erstgradigen Verwandten von KRK-Patienten im Vergleich zu gleichaltrigen Personen ohne familiäres Risiko.

Einleitung: Kombinationen von Irinotecan (CPT11) mit Folinsäure/5-Fluorouracil (FA/5-FU) (ILF) zeigten gute antitumorale Aktivität beim metastasierten kolorektalen Karzinom. Erste Daten lassen ebenfalls eine Wirksamkeit beim metastasierten Magenkarzinom vermuten.

Background: Although its incidence has been steadily decreasing in Western countries, gastric cancer remains a leading cause of cancer deaths worldwide. The detection rate of early-stage cancers is improving; nevertheless, the majority of cases is still diagnosed at later stages with a poor prognosis. Furthermore, the results that can be achieved with surgery have reached a plateau of effectiveness. Summary: Neoadjuvant chemotherapy was successfully introduced first in patients with non-curatively resectable disease. In the last decade, neoadjuvant chemotherapy has also been established in potentially curatively resectable cases and has become the state-of-the-art treatment. Esophagogastric junction (EGJ) tumors are not optimally treated with chemotherapy alone, and combined radiochemotherapy (RCT) seems to yield superior outcomes. Key Message: The use of neoadjuvant therapy has been successfully established in patients with curatively resectable disease. Neoadjuvant chemotherapy is now a cornerstone in the treatment of gastric cancer and cancer of the EGJ, although further work is needed in order to define the optimal combination regimen. Practical Implications: Neoadjuvant chemotherapy is currently the gold standard for the treatment of gastric cancer and cancer of the EGJ. Several independent studies have shown the benefits of using combination regimens that included cisplatin and 5-fluorouracil, though recently the use of the EOX (epirubicin, oxaliplatin and capecitabine) regimen has been widely accepted in this setting. Tumors of the EGJ benefit from neoadjuvant treatment with combined RCT. It should be noted that the optimal neoadjuvant regimen in EGJ tumors has not yet been defined, and the survival advantage of neoadjuvant RCT over neoadjuvant chemotherapy remains to be established in this patient population.

In Brief 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) This large, randomized trial including 618 patients compares early surgery shortly after hospital admission and delayed elective surgery after conservative treatment with moxifloxacin. Laparoscopic cholecystectomy within 24 hours was superior concerning morbidity and costs. Therefore, we believe that immediate surgery should become therapy of choice for acute cholecystitis in operable patients.

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).

Hintergrund: Einer Ascitesbildung liegt in der Regel eine fortgeschrittene Leberinsuffizienz, eine Peritonealkarzinose oder ein akut – oder chronisch-entzündliches Geschehen wie z.B. eine Pankreatitis zu Grunde. In seltenen Fällen wird das makroskopische Bild einer Peritonealkarzinose durch benigne, nicht entzündliche Veränderungen hervorgerufen.

Metal ions are present in many different biological materials, and are capable of forming strong cross-links in aqueous environments. The relative contribution of different metal-based cross-links was measured in the defensive glue produced by the terrestrial slug Arion subfuscus. This glue contains calcium, magnesium, zinc, manganese, iron and copper. These metals are essential to the integrity of the glue and to gel stiffening. Removal of all metals caused at least a 15-fold decrease in the storage modulus of the glue. Selectively disrupting cross-links involving hard Lewis acids such as calcium reduced the stiffness of the glue, while disrupting cross-links involving borderline Lewis acids such as zinc did not. Calcium is the most common cation bound to the glue (40 mmol l(-1)), and its charge is balanced primarily by sulphate at 82-84 mmol l(-1). Thus these ions probably play a primary role in bringing polymers together directly. Imine bonds formed as a result of protein oxidation also contribute substantially to the stiffness of the glue. Disrupting these bonds with hydroxylamine caused a 33% decrease in storage modulus of the glue, while stabilizing them by reduction with sodium borohydride increased the storage modulus by 40%. Thus a combination of metal-based bonds operates in this glue. Most likely, cross-links directly involving calcium play a primary role in bringing together and stabilizing the polymer network, followed by imine bond formation and possible iron coordination.

Gastric cancer remains a major health issue and a leading cause of death worldwide. While the incidence is decreasing in western countries, there has been a shift to more proximal cancers of the diffuse type, which are usually more aggressive and associated with a worse prognosis. Radical surgery still offers the only chance of long term survival, but surgery has reached a plateau of effectiveness and more aggressive approaches like "ultraradical" lymphadenectomy have not improved prognosis. There are three options to improve the situation: Earlier detection, neoadjuvant chemotherapy and adjuvant therapy. Whilst systematic gastroscopic screening makes sense in countries with a high incidence of gastric cancer, in other regions targeted investigation of risk groups including first-degree relatives of cancer patients, patients with a chronic corpus-dominant gastritis or with defined genetic abnormalities may help to detect cancer at an earlier stage. Neoadjuvant chemotherapy has meanwhile proved to significantly improve the prognosis not only in patients with a locally advanced cancer who cannot be resected for cure but but also in those who are potentially amenable to curative resection. In the largest randomised study so far reported, perioperative chemotherapy raised overall survival after 5 years from 23% to 36%. The role of adjuvant chemotherapy has been discussed for over 30 years. Meta-analyses demonstrate a small but significant effect which, however, seems to be restricted to Asian patients. In a large US-study, adjuvant radiochemotherapy appeared to significantly improve outcomes. However, less than 50% of the study patients underwent a systematic lymphadenectomy and so the results of the therapy group were not better to those of "only resected" patients in two large European studies. Thus, the indication of adjuvant (radio-)chemotherapy in gastric cancer currently remains uncertain. Endoscopists have found a therapeutic role through endoscopic resection of early cancers, introduced mainly by Japanese authors. With the development of high resolution endoscopy, endosonography and adequate equipment, the endoscopic curative resection of T1a-tumors (restricted to the mucosal layer) has been established.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal-recessive multisystemic disorder with predominant gastrointestinal involvement, presenting with variable degrees of gut dysmotility up to frank chronic intestinal pseudoobstruction. Despite major advances in understanding its basic molecular pathogenesis in recent years, the distinct mechanisms and pathoanatomical substrate underlying MNGIE-associated gastrointestinal dysmotility are still widely unknown. As yet, though their critical role in proper gastrointestinal transit in terms of spontaneous pacemaker activity and enteric neurotransmission is well established, the population of the interstitial cells of Cajal (ICC) has not been investigated in MNGIE. Therefore, we examined small bowel samples of a well-characterized MNGIE patient by using conventional histology and immunohistochemistry techniques. The ICC network was studied by immunohistochemistry for the tyrosine kinase Kit (CD117), known to reliably detect ICCs, while mucosal mast cells served as an internal and normal small bowel specimen as external controls. At a light microscopic level, no gross structural alteration of the bowel wall composition and its neuromuscular elements was noted. However, a complete absence of Kit immunoreactive cells could be demonstrated in regions where ICCs are normally abundant, while internal and external controls retained strong Kit positivity. In conclusion, our preliminary results provide a first evidence for an alteration of the ICC network in MNGIE, and support the notion that ICC loss might be an early pathogenetic event in MNGIE-associated gut motor dysfunction before significant myopathic and/or neuropathic structural changes occur.

Gastric cancer is a major health issue and a leading cause of death worldwide. The results of standard therapy remain unsatisfactory mainly because of diagnosis at the late stage of disease. Innovative strategies such as neoadjuvant chemotherapy in locally advanced cancer have improved the outcome even in operable cases. Whether an adjuvant radiochemotherapy is of benefit after curative resection including systematic lymphadenectomy remains yet unclear. Some progress has been made in the palliative setting by introducing new substances. This review examines recent advances in the systemic treatment of gastric and gastroesophageal junction cancer.

The segmental haemorrhagic colitis has been described as a particular form of antibiotics-associated colitis under penicillin therapy. A 34-year-old male presented in reduced general condition. He suffered from haematoschezia and abdominal pain. Due to a sinusitis maxillaris he had taken ciprofloxacin tablets (500 mg b. i. d.) for four days prior to the day of admission. Upon physical examination a slight general abdominal pain on palpation and some fresh blood at rectal digital examination were found. Apart from a slightly elevated CK level, all other routinely checked laboratory parameters were within normal ranges. All stool cultures remained negative for pathogenous germs. On colonoscopy we saw a severe haemorrhagic colitis with map-like mucosal lesions. It spread over the sigmoid and the distal part of the descending colon. The pathohistological assessment of step biopsies showed an acute erosive, ulcerative colitis. After cessation of antibiotic therapy the disorders subsided within three days without specific treatment. To the best of our knowledge a segmental haemorrhagic colitis under ciprofloxacin has not been described previously. A single Japanese paper mentions three cases of patients with a segmental haemorrhagic colitis under quinolones taken for four weeks before the symptoms started. In contrast, our patient developed symptoms within a couple of hours after intake of ciprofloxacin. We assume a toxic or idiosyncratic reaction to ciprofloxacin.

A 15-year-old girl was admitted in April 2004 owing to fatigue and loss of appetite. Her paediatrician had found elevated serum levels for alkaline phosphatase. The endoscopic retrograde cholangiography documented typical signs of primary sclerosing cholangitis with involvement of the small and large ducts. The liver biopsy revealed extensive septal and portal fibrosis. No evidence of inflammatory bowel disease was present. She was started on ursodeoxycholic acid therapy and improved clinically. After 22 months she presented again with rising transaminase levels up to 600 U/l. The second liver biopsy was strongly suggestive for autoimmune hepatitis besides the already known features of primary sclerosing cholangitis. Elevated levels of IgG, and elevated titres for ANA and antismooth muscle antibodies (ASMA) were also found. The duct irregularities seen on re-endoscopic retrograde cholangiography were slightly regredient as compared with the first investigation. We added prednisolone and azathioprine to the ursodeoxycholic acid and the transaminase levels dropped together with clinical improvement.

Recently, p-[123I]iodo-L-phenylalanine (IPA) was clinically validated for brain tumour imaging. Preclinical studies demonstrated uptake of IPA into pancreatic adenocarcinoma suggesting its diagnostic application in patients with pancreatic tumours. The aim was to study the tumour uptake of IPA in patients with pancreatic adenocarcinoma and to analyse its biodistribution and dosimetry to assess the radiation dose resulting from its diagnostic use. Patients, methods: Seven patients with pancreatic adenocarcinoma underwent whole-body scintigraphies and SPECT up to 24 h after administration of 250 MBq of IPA. Tumour uptake of IPA was assessed visually. Time activity curves and the corresponding residence times were determined for whole-body, kidneys, liver, spleen, lung, heart content, brain, and testes. Mean absorbed doses for various organs and the effective dose were assessed based on the MIRD formalism using OLINDA/EXM. Results: IPA exhibited no accumulation in proven manifestations of pancreatic adenocarcinomas. IPA was exclusively eliminated by the urine and showed a delayed clearance from blood. Residence times were 0.26 ± 0.09 h for kidneys, 0.38 ± 0.19 h for liver, 0.15 ± 0.07 h for spleen, 0.51 ± 0.20 h for lungs, 0.22 ± 0.07 h for heart content, 0.11 ± 0.05 h for brain, 0.014 ± 0.005 h for testes and 6.4 ± 2.2 h for the remainder. The highest absorbed doses were determined in the urinary bladder wall and in the kidneys. According to the ICRP 60 the effective dose resulting from 250 MBq IPA was 3.6 ± 0.7 mSv. Conclusion: Para-[123I]iodo-L-phenylalanine can be used in diagnostic nuclear medicine with acceptable radiation doses. Besides its proven validity for brain tumour imaging, IPA does not appear to be suitable as tracer for pancreatic cancer.