Arndt Hribaschek

Outpatient Therapy with Gemcitabine and Docetaxel for Gallbladder, Biliary, and Cholangio-Carcinomas

AbstractPurpose. The prognosis of patients withbiliary tree carcinomas is very poor. Thediagnosis often occurs at an advancedstage, when curative resection is notpossible. We combined gemcitabine anddocetaxel to optimize the palliativetherapy for patients with gallbladder,biliary, and cholangio-carcinomas on anoutpatient basis. Patients and methods. Patients withhistologically proven biliary treecarcinomas and a WHO performance status<2 received gemcitabine 1000 mg/m2followed by docetaxel 35 mg/m2 weekly for 3weeks followed by 1 week of rest. Results. Forty-three patients, 14males/29 females, with an average age of63.3 years (range, 41 to 78) have beenenrolled since 1998; 37 have completedtreatment. So far, 168 cycles (range, 1 to16) have been administered. All 43 patientswere included in the response and toxicityassessments. There are no completeremissions; however, 4 (9.3%) patientsachieved partial remission, 1 (2.3%) had aminimal remission, and 24 (55.8%)reached disease stabilization for a medianperiod of 5.2 months. Fourteen (32.6%)patients progressed. The median overallsurvival rate is currently 11.0 months. Grade 3 hematologic toxicities wereinfrequent, and there were no grade 4hematologic toxicities. Grade 3 leukopeniawas reported in 4 (9.3%) patients, grade 3thrombozytopenia in 1 (2.3%) patient, andgrade 3 anemia in 1 (2.3%) patient.Twenty-eight (65.1%) patients had grade3/4 alopecia, 8 (18.6%) hadnausea/vomiting, and 2 (4.6%) hadmucositis. Conclusion. The combination ofgemcitabine/docetaxel is an effective andwell tolerated therapy for patients withadvanced or metastatic gallbladder,biliary, and cholangio-carcinomas.

Intermuscular Chondrolipoma of the Thigh: The Diagnostic Way of a Rare Entity

Cartilaginous metaplasia in lipomas (chondrolipoma) is rare and mainly encountered in large-sized, long-standing lipomas. Chondrolipomas can be found at almost any site of the body, particularly in the connecting tissue of the skeletal system, breast, pharynx, and nasopharynx. We report on an intermuscular tumor of the thigh in a patient who suffered from lipomatosis in his past medical history. We describe how the diagnosis of chondrolipoma was reached and discuss the differential diagnoses.

Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma

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 ≧ 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.

Intraperitoneal Versus Intravenous CPT-11 Given Intra- and Postoperatively for Peritoneal Carcinomatosis in a Rat Model

PurposePeritoneal 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.MethodsWe induced intraperitoneal tumor growth using a tumor cell transfer model (106 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.ResultsCPT-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.ConclusionCPT-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.

Comparison of Intraperitoneal with Intravenous Administration of Taxol in Experimental Peritoneal Carcinomatosis

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 (106 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.

Successful conservative treatment of chylous ascites as rare intermediate complication after resection of an aboral esophageal carcinoma

Correspondence: Frank Meyer Department of Surgery, University Hospital, Leipziger Strasse 44, D-39120 Magdeburg, Germany Tel +49 391 67 15500 Fax +49 391 67 15570 Email frank.meyer@med.ovgu.de Background: Chylous ascites is an uncommon symptom that needs specifi c expertise with regard to the diagnostic and therapeutic management. Methods: We are reporting on an uncommon and exceptional case of a 65-year-old man in whom postoperative chylous ascites was diagnosed using both daily ascites inspection and laboratory investigation. Treatment was initiated according to a previously established protocol, which summarized our own experiences and recommendations from the literature. Results: The patient showed a prolonged postoperative course after partial esophagectomy of the aboral segment (2-cavity intervention) because of Barrett carcinoma (pT3N1M0G3R0), including lymphadenectomy and esophagogastric anastomosis, which was initially complicated by i) hemorrhage (d2), leading to relaparotomy, ii) prolonged weaning maneuver, and iii) suspicion of chylous ascites characterized by beige and milky effusion out of the abdominal drainage after appendicostoma placement for colonic decompression (d28). Diagnosis was confi rmed by laboratory detection of chylomicrons and triglycerides of 4.8 mmol/L. After an observation period of two weeks, total parenteral nutrition (TPN) was initiated for 5 weeks. This resulted in the clearance of ascites (decrease of its amount partially after 5–10 d, completely after 20 d) and fi nal removal of the abdominal drain. There were no further abnormal symptoms or signs. Conclusions: The established therapeutic concept favoring conservative long-term TPN and avoiding reintervention, which was repeatedly used in rare cases of chylous ascites, is suitable to achieve spontaneous healing of lymphatic leakage by diminishing lymphatic fl ow due to decreased i) enteral fat absorption and ii) transport along the lymphatic vessels as shown in this exceptional case. To our best knowledge, this is only the sixth case with chylous ascites after esophagectomy reported in the literature.

Intra- und frühe postoperative Chemotherapie in die Bauchhöhle mittels Gemcitabine kann das postoperative Auftreten einer Peritonealkarzinomatose verhindern

Intra- and Early Postoperative Chemotherapy in the Abdominal Carity by Means of Gemcitabine Can Prevent the Postoperative Occurrence of a Peritoneal Carcinomatosis Hintergrundc Im Fall einer Peritonealkarzinomatose gibt es keine kurative Behandlung fur jeglichen Tumor in der Peritonealhohle. Das Ziel dieser experimentellen Studie bestand darin, das Praventivpotential einer intra- oder fruhen postoperativen lokalen Gemcitabineverabreichung in die Bauchhohle gegen eine Peritonealkarzinomatose zu prufen. Methode: Die Peritonealkarzinomatose wurde in mannlichen WAG-Ratten (n = 18) durch den Transfer von 5 × 1.000.000 Zellen der Adenokarzinom-Zelllinie CC-531 via Minilaparotomie unter Allgemeinanasthesie induziert. Dreisig Tage nach Zelltransfer wurde die Peritonealkarzinomatose post mortem durch histologische Untersuchung an Proben des Peritoneums bestatigt. Die Extension der Karzinomatose wurde mittels i) Zahlen der Tumorknoten pro qcm (Mittelwert mehrfacher Zahlung) und ii) Bestimmung der Tumorgewichts (Gewicht von grosem Netz plus reseziertem Mesenterium) ermittelt. Die Ratten wurden in 3 Gruppen — unterteilt (n = 6 pro Gruppe). Gruppe 1 (Kontrollen); Gruppe 2: Simultan mit dem Tumorzelltransfer intraperitoneal (i.p.) wurden 24 mg/kg Gemictabine verabreicht; Gruppe 3: Postoperative i.p. Irrigation mit 24 mg/kg Gemictabine via vorher implantiertes Portsystem an den Tagen(d) 15,21 & 27. Ergebnisse: Am 30. postoperativen Tag zeigten alle 6 Kontrolltiere ein extensives Tumorwachstum am Peritoneum und grosen Netz, was fur eine Peritoneal-karzinomatose sprach. Dagegen zeigte keines der Tiere aus Gruppe 2 irgendwelche Anzeichen von Tumorwachstum. Wahrend alle Ratten aus Gruppe 3 i.p.-Tumorwachstum aufwiesen, resultierte die fruhe postoperative Behandlung mit Gemcitabine in einer signifikanten Reduktion der Zahl der Lymphknoten und der Tumormasse im Vergleich zu den Kontrollen. Zusammenfassungg: Die unmittelbare, d.h. simultane intraoperative Applikation eines Zytostatikums wie Gemcitabine in die Bauchhohle kann der Ausbildung einer Peritoneal-karzinomatose durch auftretende Tumorzellen vorbeugen, wohingegen die fruhe postoperative lokoregionare Chemotherapie in die Bauchhohle ihre Schwere mindern kann

Oxaliplatin und CPT-11 sind wirksam in der Prävention jedoch nicht in der Behandlung experimentell erzeugter Peritonealkarzinomatose

After surgical resection of colorectal carcinoma, the high local recurrence rate at the original tumor or the peritoneal site remains an unsolved problem. Currently, there are no established standardized therapy protocols for the prevention or treatment of peritoneal carcinomatosis. CPT-11 and Oxaliplatin are novel cytostatic agents, which can provide beneficial effects in the treatment of patients with advanced colorectal cancer. The aim of our study was to investigate whether these substances can inhibit intraperitoneal (i. p.) tumor growth using a rat model of experimental carcinomatosis. Animals were devided into three groups including controls. In group 1, antineoplastic agents were administered directly into the peritoneal cavity following tumor cell transfer, whereas in group 2, substances were given as early postoperative i.p. chemotherapy (d5, 10 & 15 after cell transfer) via port-a-cath. Group 3: i.p. chemotherapy (15 d interval after cell transfer) was administered with the intention of reducing a manifest peritoneal carcinomatosis. The results indicated that CPT-11 and Oxaliplatin were significantly effective in reducing intraperitoneal tumor growth after direct i.p. application during laparotomy for tumor cell transfer. In addition, i.p. administration of CPT-11 or Oxaliplatin also inhibited tumor growth using short postoperative intervals of i.p. chemotherapy. However, the chemotherapeutic protocol was not effective after manifestation of peritoneal carcinomatosis, showing that 1) CPT-11 and Oxaliplatin are potential agents for this setting and 2) it appears to be essential to focus on early administration of chemotherapy in particular for prevention of peritoneal carcinomatosis.